Diabetes Research News

Get the most recent diabetes research news, delivered straight to your inbox

Advances in Therapeutic Treatment for Type 1 Diabetes without Immune Suppression

One approach that researchers have been exploring to treat type 1 diabetes (T1D) is cell therapy. By introducing new insulin-producing beta cells, or other types of cells, scientists strive to once again, enable those with T1D to produce insulin in response to blood glucose levels. One common challenge with this technique is a renewed autoimmune response, or loss of function. Cell therapy typically requires immune suppression which can put individuals at risk for other complications.

However, in a recent study, researchers tested a new method of transplanting therapeutic beta cells by using a retrievable device with a silicone reservoir. The cells are further protected by a porous polymeric membrane that allows cell killing macrophages to enter the device without destroying the transplanted cells, or that prevents them from entering the cell at all.

When tested in immunocompetent mice, the device supported normal blood glucose levels for more than 75 days without the need for immunosuppression. The transplanted cells were able to effectively produce erythropoietin, which in turn improves oxygen supply to the body, and also generates insulin to manage blood sugar levels.

This is a notable step forward in improving cell therapy for the treatment of type 1 diabetes. More research and testing are required to determine how this process translates into human models. Researchers have been trying to limit or eliminate the need for immune suppression while transplanting healthy pancreatic, islet, and stem cells into the body to control blood glucose levels.

Dan Anderson, Ph.D., a member of DRC’s Scientific Review Committee, is the senior author of the article, which was published recently. DRC is excited to see where these advances may lead and what it could mean for the future of cell transplantation techniques and cell therapy for T1D. The organization provides critical funding for a wide range of projects related to improving diagnosis, treatment and prevention of the disease. Learn more about current studies and how to support these efforts by visiting http://drcnew.awp.uxtesting.net.

Learn More +

Differentiating Between Childhood-Onset and Adult-Onset Type 1 Diabetes

Although many cases of type 1 diabetes (T1D) emerge in childhood because it is an autoimmune disorder unrelated to diet or exercise, there are some individuals who develop T1D in adulthood. This condition is referred to as latent autoimmune diabetes in adults, or LADA. LADA shares characteristics with both type 1 and type 2 diabetes, but it is more closely related to type 1.

Researchers estimate that around 10 percent of individuals diagnosed with T2D actually have LADA. This is discovered when patients do not respond as expected to common T2D treatment. Just like with T1D, their body’s immune system mistakenly attacks and destroys insulin-producing beta cells that are essential for blood sugar regulation.

Up to this point, autoantibody screening was the primary way of differentiating between LADA, T1D, and T2D, but this can be an expensive process. However, a recent study found that there may be genetic differences between these conditions that are significant enough to serve as a more affordable yet still reliable way of diagnosing diabetes type.

With T1D, when researchers examined the major histocompatibility complex (MHC) and “control for T1D genetic variants in one part of the MHC, other variants associated with T1D appear in another part of the MHC.” When they conducted the same test on LADA patients, the results were not the same. In controlling for T1D genetic variants, there was no association in another part of the MHC. Furthermore, they saw the same differences in outcomes when a sensitivity test was conducted.

These genetic differences may help medical professionals more accurately diagnose individuals with LADA and provide more effective treatment sooner. Additional research is necessary to determine whether these findings hold true across multiple ethnicities.

It is these types of studies that help other scientists advance their own research regarding type 1 diabetes in order to improve diagnosis, treatment, and management of the disease. Diabetes Research Connection (DRC) provides critical funding for early-career scientists pursuing novel research studies on T1D. To learn more or support current projects, visit http://drcnew.awp.uxtesting.net.

Learn More +

Increasing Protective Factors to Reduce Risk of Type 1 Diabetes

Despite decades of research, scientists have yet to develop a cure for type 1 diabetes since it is a complex disease that is impacted by and interacts with many processes within the body. However, they have made significant advancements in understanding and managing the disease. Now, more focus is being put on preventing the development of type 1 diabetes.

In a recent study, researchers at the Pacific Northwest National Laboratory found that by increasing levels of growth differentiation factor 15 (GDF15) in non-obese diabetic mice, they were able to reduce the risk of developing type 1 diabetes by more than 50 percent. Although there are more than 387 pancreatic proteins in the body associated with T1D, the researchers discovered that GDF15 was significantly depleted in pancreatic beta cells of individuals with T1D.

By increasing GDF15 levels in the non-obese diabetic mice, it helped to protect islet cells from immune system attack. Researchers are seeking to determine whether this may be used to create more effective therapies for the treatment and prevention of the disease in humans. While more research is needed, it is a step in the right direction.

Diabetes Research Connection (DRC) is following these findings to see how they impact future diabetes research and treatment options. It is these types of studies that open doors for advancements in the field and an increased understanding of the disease. The DRC supports early-career scientists in pursuing novel, peer-reviewed research studies focused on the prevention, treatment, and management of T1D and eventually finding a cure. To learn more about current projects and support these efforts, visit http://drcnew.awp.uxtesting.net.

Learn More +

Genetic Testing May Improve Prediction of Type 1 Diabetes Risk

The cause of type 1 diabetes is complex. There is not a single gene responsible for the disease, and both genetics and environment play a role. Plus, there is currently no way of preventing the disease from occurring. However, scientists believe that they can better predict which children and teenagers are at higher risk so their health can be monitored more closely and treatment started before they develop potentially life-threatening diabetic ketoacidosis.

A recent study found that a simple genetic test that compares an individual’s gene profile to 82 genetic sites that are known to be associated with type 1 diabetes can identify those who are most at risk. The test only costs $7 and uses a saliva sample, so no blood draws or painful testing are required. If an individual is flagged as high risk, they can then have autoantibody screening conducted to look for the presence of four islet autoantibody biomarkers of the disease. The presence of two or more autoantibodies further identifies an individual at increased risk. Autoantibody tests are slightly more expensive at $75 each.

While family history does increase risk of type 1 diabetes, it is not a guaranteed indicator, and more than 90% of people who develop the disease do not have a family history. This genetic test could help to differentiate between those at high risk and those at low risk so there are fewer unnecessary tests that occur, and individuals who could benefit from closer monitoring can be more accurately identified.

According to the study, “The general population risk of type 1 diabetes is about 4 out of 1000, and those with a positive genetic test now have a risk of about 4 out of 100.” Testing may allow doctors to provide more targeted care and treatment for the disease and support individuals in better managing their health. As research continues to advance, scientists learn more about the risk factors, biomarkers, genetic sites, and environmental factors that all contribute to the development of type 1 diabetes. In turn, this can enhance prediction, prevention, and treatment of the disease.

Diabetes Research Connection (DRC) supports early-career scientists in growing the body of knowledge that exists regarding type 1 diabetes by providing critical funding for research projects. Studies are focused on preventing and curing the disease as well as minimizing complications and improving quality of life. Learn more about current projects and how to support these efforts by visiting http://drcnew.awp.uxtesting.net.

Learn More +

Type 1 Diabetes Poses a Significant Financial Burden

Managing type 1 diabetes (T1D) is not only time consuming, it is also expensive. Costs include not only the basics to manage the disease such as testing supplies, insulin, continuous glucose monitors, and insulin pumps, but also those related to hospital care for complications or outpatient care. In addition, there are lost wages due to disease-related situations, as well as indirect costs. These expenses can quickly add up.

A recent study looked at the estimated lifetime economic burden for individuals with T1D versus those without. The results showed that the difference between the two groups over the course of 100 years (a lifetime), was $813 billion. The model projected costs for 1,630,317 individuals with T1D and the same number without. It followed simulated patients year by year from the time they were diagnosed until they passed away.

According to the study, “Diabetes contributes $237 billion in direct medical costs per year or 7% of the nation’s $3.3 trillion spent on health care, which is higher than the annual health care expenditures for other chronic diseases, such as cancer (5%) and heart disease/stroke (4%).”

Not only did individuals without T1D experience lower costs, they also had higher life expectancy rates. Patients with T1D are at increased risk for disease-related complications which can further impact life expectancy and financial burden. Currently, T1D is a progressive disease, and it is something that affects individuals for the rest of their lives because there is no known cure. It must be managed 24 hours a day, 7 days a week, 365 days a year.

The extreme difference in lifetime societal burden and economic burden between these two groups demonstrates the need for continued research related to T1D. The ability to prevent or delay disease development or progression, or to cure the disease, could have major financial cost savings. The results of this study were estimated given available data and modeling capabilities, so they may underestimate the true impact.

There were also certain limitations to the study, including data that was only recent up to 2016 and did not include costs associated with CGMs, insulin pumps, or hybrid artificial pancreas systems. Complication-related costs were derived from data on patients with type 2 diabetes because it was not available for patients with type 1 diabetes. However, the general message does not change: finding a way to delay, prevent, or eliminate disease progression is essential, in addition to minimizing complications.

Diabetes Research Connection (DRC) is committed to advancing research around type 1 diabetes by providing critical funding to early-career scientists. Through their novel, peer-reviewed studies, they can improve understanding of the disease as well as treatment options. To learn more about current projects and support these efforts, visit http://drcnew.awp.uxtesting.net.

Learn More +

Studying Environmental Factors Related to Type 1 Diabetes

While genetics do play a role in the development of type 1 diabetes (T1D), researchers also believe that environment contributes as well. There is no singular cause of T1D, and all of its risk and protective factors are yet unknown. However, one study is striving to build a comprehensive understanding of diverse environmental factors and the role they may play in children developing T1D.

Researchers launched The Environmental Determinants of Islet Autoimmunity (ENDIA) several years ago and recently received an additional $8.25M in funding to keep it going for another three years. Over the past seven years, they have enrolled 1,500 participants, which includes babies ranging from pregnancy up to six months in age who have at least one immediate relative with T1D. The babies are seen every three to six months until they reach at least age three.

The study looks at a wide range of environmental factors in an effort to gain a better understanding of what increases or decreases risk of developing type 1 diabetes. Factors include “growth during pregnancy and early life, the method of delivery (natural birth versus caesarean section), the mother’s nutrition during pregnancy, infant feeding (breastfeeding and/or formula), the duration of breastfeeding and the child’s nutrition, the child’s immune system and when the child received vaccines and exposure to viruses during pregnancy and early life.”

Not only did it take a long time to recruit participants, it will take several years to gather and analyze the long-term data in order to identify potential risk or protective factors and how each child was affected. With millions of people living with T1D, this study may help to improve treatment and prevention in the future, possibly leading to a vaccine one day.

Diabetes Research Connection (DRC) will continue to follow this study and see how results progress and what discoveries are made. In the meantime, the organization provides critical funding for early career scientists pursuing research on various facets of T1D. Studies are focused on preventing or curing diabetes, as well as reducing complications and improving quality of life for individuals living with the disease. Visit http://drcnew.awp.uxtesting.net to learn more about current projects and support these efforts.

Learn More +

Improvements in Stem Cell Therapies Reverse Type 1 Diabetes in Mice

More than one million people in the United States are living with type 1 diabetes according to statistics from the Centers for Disease Control and Prevention. There is a strong push to improve management of the disease and find a cure. The more researchers learn about T1D, the more precise their prevention and treatment methods become.

A recent study reveals that improvements in stem cell therapy have reversed T1D in mice for at least nine months and, in some cases, for more than a year. One of the challenges that scientists have faced with using human pluripotent stem cells (hPSCs) is that is can be difficult to zero differentiation in on one specific type of cell. Often multiple types of pancreatic cells are produced. While there may be an abundance of cells that scientists want, the infiltration of excess cells that are not needed diminishes their impact (even though they are not harmful).

Scientists at the Washington University School of Medicine in St. Louis have found a way to generate insulin-producing beta cells without creating as many irrelevant cells. Their approach focuses on the cell’s cytoskeleton, which is its inner framework. Through this process, they were able to produce vast amounts of beta cells that are able to normalize blood glucose levels.

When transplanted into severely diabetic mice (blood glucose levels above 500 mg/dL), the cells effectively reversed the effects of diabetes and brought blood sugar levels down into target range within two weeks. Normoglycemia was maintained for at least nine months.

This is a major step forward in stem cell therapy and the use of hPSCs to potentially cure diabetes one day. There is still more testing and research that needs to be done before this approach is applied to human trials.

Ongoing research is essential for finding a cure for T1D. Diabetes Research Connection supports these efforts by providing critical funding to early career scientists pursuing novel research studies on the disease. By giving them the means to complete their projects, these researchers can continue to advance knowledge and treatment options. Learn more about current studies and how to help by visiting http://drcnew.awp.uxtesting.net.

Learn More +

Improved Beta Cell Function of Transplanted Islet Cells in T1D

One of the major challenges of using transplanted islet cells in the treatment of type 1 diabetes is cell death. Due to cellular stressors, poor oxygenation or vascularization, autoimmune response, and other factors, not all transplanted cells survive, and this can make treatment less effective. The body needs functional insulin-producing islet cells in order to effectively regulate blood sugar levels.

A recent study found that coculturing allogeneic islet beta cells with mesenchymal stromal cells (MSCs) may improve not only cell survival, but function as well. After donor cells are procured, they must be cultured and tested before being transplanted. This can generate significant cellular stress including hypoxia or low oxygenation, which can in turn lead to cell death. However, researchers found that MSCs support islet cells during this culture period by improving oxygenation and insulin secretion.

They also found that in response to these stressors, MSCs actually initiate mitochondria transfer to the islet beta cells.  This may improve mitochondrial ATP generation which plays an integral role in controlling insulin secretion. As a result, as glucose levels around the beta cells increased, so did their production and secretion of insulin.

Researchers experimented with this coculturing process with both mouse cells and human cells and found that human cells have a greater response and higher level of MSC-mediated mitochondria transfer that occurs. Though more extensive testing is necessary, these results show that MSCs may be an essential part of clinical islet transplantation and improved efficacy of beta cell function in treating individuals with type 1 diabetes.

Diabetes Research Connection (DRC) is interested to see how this study evolves moving forward and what it may mean for future therapeutic treatments for the disease. The DRC, though not involved in this study, provides critical funding for early career scientists pursuing novel, peer-reviewed research projects for type 1 diabetes. Learn more about current projects or how to support these efforts by visiting http://drcnew.awp.uxtesting.net.

Learn More +

Type 1 Diabetes Vaccine Shows Positive Results

In an effort to prevent or delay the onset of type 1 diabetes, researchers have been striving to create an effective vaccine. One of the challenges is that there are many different subgroups of type 1 diabetes, meaning not all patients respond the same. A recent study found that patients who had a specific human leukocyte antigen (HLA) showed a “positive and statistically significant dose-dependent treatment response” to the Diamyd vaccine, especially when given four doses rather than two.

Compared to patients who received a placebo, those who received a higher number of doses of the Diamyd vaccine had a “statistically significant treatment effect of approximately 60%” within 15 months. These findings may help to advance the development of antigen-specific immunotherapy options for individuals with type 1 diabetes leading to improved treatment or management of the disease.

Diabetes Research Connection (DRC) is interested to see how this vaccine continues to evolve moving forward and what it could mean for the prevention of type 1 diabetes in the future. Though not involved with this study, the DRC provides early career scientists with funding necessary to conduct novel, peer-reviewed research projects around type 1 diabetes in an effort to improve understanding, prevention, treatment, and management of the disease. To learn more or donate to a current project, visit http://drcnew.awp.uxtesting.net.

Learn More +

Improved Protection for Transplanted Stem Cell-Derived Islets

Insulin-producing beta cells are essential for effective blood sugar control. However, in individuals with type 1 diabetes, these cells are mistakenly destroyed by the immune system. That means exogenous insulin must be used instead to manage blood sugar. For years, scientists have been researching ways to replace or reproduce these islet cells. Two of the most common challenges faced, however, have been the need for long-term immunosuppression to protect transplanted cells from rejection, and limited availability of donor cells.

A recent study found that an improved source of encapsulation may protect islet cells from an immune response without decreasing their ability to secrete insulin. By using a conformal coating that is only a few tens of micrometers thick (as opposed to hundreds of micrometers thick), not only could insulin flow more freely through the encapsulation, so could oxygen, nutrients, and glucose as well. Yet larger immune cells were still unable to penetrate the barrier. In addition, the thinner coating allowed for more cells to be contained in a smaller space, and the capsule could be implanted in a wider range of locations so long as there was strong vascular function.

The encapsulated cells were implanted in NOD-scid mice and compared with non-coated stem cells as well as human islets. There were no statistically significant differences in performance of the cells and their ability to regulate glucose levels. The mice all showed a reversal in diabetes with the transplanted cells and returned to hyperglycemia once the cells were explanted.

The use of a microencapsulation method allows for more variability in placement of transplanted cells and helps protects against hypoxia-induced islet death and cell rejection. Furthermore, the thinner coating enabled islets to obtain better oxygenation because they are closer to blood vessels. It also allowed insulin to be secreted more quickly because it flowed more freely through the barrier.

One drawback that researchers noted was that encapsulated islets are unable to shed dead cells because they are contained within the capsule and have a lower absolute quantity of insulin secretion when compared to non-coated stem cell-derived islets.

Through this study, the researchers concluded that, “CC (conformal-coated) mouse islets can reverse diabetes long-term in a fully MHC-mismatched model.” While additional research is necessary to explore the effectiveness of this process in humans, it is a step in the right direction toward one day potentially curing type 1 diabetes.

Though not involved with this study, Diabetes Research Connection (DRC) stays abreast of the latest advancements in the field and provides critical funding to early career scientists pursuing novel research studies for type 1 diabetes. It is through these types of projects that researchers are able to improve quality of life for individuals living with the disease and move closer to finding a cure. To learn more about current DRC-funded projects or support these efforts, visit http://drcnew.awp.uxtesting.net.

 

Learn More +

Exploring Why the Immune System May Attack Insulin-Producing Beta Cells

Insulin-producing beta cells are essential for effective blood sugar control. However, in individuals with type 1 diabetes, these cells are mistakenly destroyed by the immune system. That means exogenous insulin must be used instead to manage blood sugar. For years, scientists have been researching ways to replace or reproduce these islet cells. Two of the most common challenges faced, however, have been the need for long-term immunosuppression to protect transplanted cells from rejection, and limited availability of donor cells.

A recent study found that an improved source of encapsulation may protect islet cells from an immune response without decreasing their ability to secrete insulin. By using a conformal coating that is only a few tens of micrometers thick (as opposed to hundreds of micrometers thick), not only could insulin flow more freely through the encapsulation, so could oxygen, nutrients, and glucose as well. Yet larger immune cells were still unable to penetrate the barrier. In addition, the thinner coating allowed for more cells to be contained in a smaller space, and the capsule could be implanted in a wider range of locations so long as there was strong vascular function.

The encapsulated cells were implanted in NOD-scid mice and compared with non-coated stem cells as well as human islets. There were no statistically significant differences in performance of the cells and their ability to regulate glucose levels. The mice all showed a reversal in diabetes with the transplanted cells and returned to hyperglycemia once the cells were explanted.

The use of a microencapsulation method allows for more variability in placement of transplanted cells and helps protects against hypoxia-induced islet death and cell rejection. Furthermore, the thinner coating enabled islets to obtain better oxygenation because they are closer to blood vessels. It also allowed insulin to be secreted more quickly because it flowed more freely through the barrier.

One drawback that researchers noted was that encapsulated islets are unable to shed dead cells because they are contained within the capsule and have a lower absolute quantity of insulin secretion when compared to non-coated stem cell-derived islets.

Through this study, the researchers concluded that, “CC (conformal-coated) mouse islets can reverse diabetes long-term in a fully MHC-mismatched model.” While additional research is necessary to explore the effectiveness of this process in humans, it is a step in the right direction toward one day potentially curing type 1 diabetes.

Though not involved with this study, Diabetes Research Connection (DRC) stays abreast of the latest advancements in the field and provides critical funding to early career scientists pursuing novel research studies for type 1 diabetes. It is through these types of projects that researchers are able to improve quality of life for individuals living with the disease and move closer to finding a cure. To learn more about current DRC-funded projects or support these efforts, visit http://drcnew.awp.uxtesting.net.

 

Learn More +

Understanding the Impact of GABA on Insulin Secretion and Regulation

In order to manage blood glucose levels, pancreatic beta cells release insulin in pulses. These bursts of insulin help the body to regulate and stabilize blood sugar. In individuals with type 1 diabetes, however, the pancreatic beta cells that normally secrete insulin are mistakenly destroyed by the body. This leaves the body unable to effectively regulate blood sugar on its own. Understanding the interaction between insulin-producing beta cells and other processes in the body may help researchers improve treatment and prevention options when it comes to diabetes.

A recent study examined the different roles gamma amino-butyric acid (GABA) plays in cell activity. In the brain, GABA is released from nerve cell vesicles each time a nerve impulse occurs. The GABA prepares cells for subsequent impulses by working as a calming agent. Researchers previously believed that this process worked in much the same way in the pancreas.

However, in the pancreas, GABA is evenly distributed throughout the beta cells rather than contained within small vesicles, and it is transported via the volume regulatory anion channel. This is the same channel that helps stabilize pressure inside and outside of cells so that they maintain their shape. Furthermore, research showed that GABA is released in a similar pattern and frequency as pulsatile in vivo insulin secretion. Just like in the brain, GABA plays an integral role in preparing and calming cells to make them more receptive to subsequent insulin pulses.

Scientists are interested in learning more about how GABA signaling can support the regulation of insulin secretion and potentially protect cells from autoimmune activity. This opens new doors for biomedical research that has the ability to impact diabetes care.

It is encouraging to see different types of researchers all coming together and learning from and building upon one another’s work in order to advance understanding, prevention, and treatment of various diseases, including diabetes.

Diabetes Research Connection stays abreast of the latest discoveries in the field and supports early career scientists in contributing to this body of work by providing critical funding for their projects. It is essential that scientists have the resources to pursue novel research in order to develop improved prevention, treatment, and management options for type 1 diabetes. Learn more and support current projects by visiting http://drcnew.awp.uxtesting.net.

Learn More +

Could Higher-Dose and Lower-Dose Insulin Glargine be Equally Effective in Managing Type 1 Diabetes?

In an effort to maintain greater blood-glucose stability throughout the day and minimize highs and lows, some individuals with type 1 diabetes use insulin glargine, which is a once-a-day, long-acting insulin. It is an analogue, or laboratory-created, insulin which has been modified to act more uniformly in managing glucose levels.

Insulin glargine comes in varying strengths, and a recent study found that there were no significant differences in safety or effectiveness between insulin glargine 100 U/mL and insulin glargine 300 U/mL when administered in children and adolescents. Data from 463 EDITION JUNIOR study participants between the ages of 6 and 17 were compared over 26 weeks. Of those participants, 233 were randomly assigned to insulin glargine 300 U/mL, and 228 were randomly assigned to insulin glargine 100 U/mL. Both groups continued to follow their normal routine for mealtime insulin but injected insulin glargine once per day.

Results showed that all participants experienced a reduction in HbA1c levels over the 26 weeks. However, there were fewer instances of severe hypoglycemia among participants using the insulin glargine 300 U/mL, though overall, results were comparable between groups. Both insulins were effective in achieving target study endpoints and did not demonstrate any unexpected safety concerns.

In comparing insulin glargine 100 U/mL and insulin glargine 300 U/mL, researchers may be able to use insulin glargine 300 U/mL as yet another treatment option for children and adolescents with type 1 diabetes. It is currently under review by the FDA, and researchers are evaluating data from a six-month safety follow-up.

It is encouraging to see that more options are being explored to meet the needs of individuals living with type 1 diabetes in order to maintain target glucose levels with fewer fluctuations. Diabetes Research Connection (DRC) will continue to follow these types of studies to see how they impact the future of diabetes management and accessibility to care.

DRC provides critical funding for early career scientists pursuing novel, peer-reviewed research studies for type 1 diabetes. Projects aim to improve prevention and treatment of the disease, as well as enhance quality of life and eventually find a cure. To learn more about current studies and support these efforts, visit http://diabetesresearchconnection.org.

Learn More +

Advancements in Characterizing Type 1 Diabetes Heterogeneity

No two people with type 1 diabetes are exactly the same. Each experiences disease progression differently, and the genetic and biological factors that impact this process differ as well. This can make understanding how type 1 diabetes initially develops and the risk factors involved more challenging.

A recent study examined islet autoimmunity and heterogeneity across a group of 80 individuals diagnosed with juvenile-onset type 1 diabetes. Some had only been recently diagnosed while others had been living with the disease for many years. The study evaluated immunological, genetic, and clinical differences between individuals in order to create more detailed profiles and stratify findings.

Blood samples were taken and testing conducted to determine T-cell response to various beta cell antigens including GAD65, islet antigen-2 (IA-2), preproinsulin (PPI), and defective ribosomal product of the insulin gene (INS-DRIP). Results show that some individuals were high responders showing T-cell proliferation for all four beta cell antigens, some were intermediate responders showing proliferation to one to three beta cell antigens, and the rest were non-responders who did not show any T-cell proliferation response to the tested beta cell antigens.

In addition, more than 80 percent of participants were categorized as high risk by having an HLA-DR-DQ genotype that is associated with development of type 1 diabetes. High responders also had higher non-HLA genetic risk scores than the other two groups. Another interesting finding was that individuals who had longer disease durations also showed an increase in beta cell-specific T-cell proliferation.

Though a larger study is needed to further build out full immunological heterogeneity and explore the interactions between different variables, this study is a strong starting point. Better understanding the complete profile of individuals with type 1 diabetes and how their body responds to different factors could lead to more individualized treatment to help manage the disease. Researchers can tailor treatment toward which beta cell antigens a person responds to, whether they or not they have high HLA-DR-DQ risk or not, as well as other variables.

The body of knowledge surrounding type 1 diabetes is always growing and improving. This is critical to advance prevention and treatment options. Diabetes Research Connection (DRC) supports early career scientists in pursuing novel research studies in order to continue moving understanding forward. Learn more about current projects and how to help by visiting http://drcnew.awp.uxtesting.net.

Learn More +

Unraveling the Process of Fetal Pancreas Development

Cell replacement therapy has been at the forefront of type 1 diabetes research for many years. Researchers have explored different ways to reintroduce insulin-producing beta cells into the pancreas or stimulate the body to begin producing these cells once again. A major challenge is often rejection of the cells by the body, or limited sustainability due to poor vascularization or an autoimmune response.

However, a recent study looks at the function of human multipotent progenitor cells (hMPCs) during development of the pancreas in human fetuses. Scientists were able to safely recover live cells from fetal tissue during the second trimester of development. They found that hMPCs located within the tip of the epithelium contained both SOX9 ad PTF1A transcription factors. However, according to their research, “tip cells did not express insulin, glucagon, or amylase,” which demonstrated their lack of lineage-specific markers. That means that they were uncommitted cells and could potentially differentiate into any of the three major types of pancreatic cells: ductal, endocrine, or acinar.

The proportion of SOX9+/PTF1A+ cells greatly decreased during the second trimester, however.  They accounted for more than 60% of cells up to 13.5 weeks of gestation, but after that, there was a significant decrease over the following weeks to less than 20%. During the second trimester, hMPCs also begin the process of branching morphogenesis and divide between tip and truck cells.  Truck cells become ductal and endocrine cells, but tip cells become acinar cells.

As researchers gain a deeper understanding of how the pancreas develops and how cell expression and differentiation takes place, they may be able to enhance cell replacement therapy options. According to the study, “This first ‘snapshot’ of the transcriptional network of human pancreatic progenitors opens new avenue in understanding human pancreas development, pancreatic specification and supports our ultimate goal of understanding possible mechanisms for pancreas regeneration.”

Diabetes Research Connection (DRC) is interested to see how this research may influence future treatment options for individuals with type 1 diabetes.  By better understanding the pancreas at a cellular level, it could stimulate more advanced therapies. The DRC provides critical funding for novel, peer-reviewed research studies focused on the diagnosis, treatment, and eventual cure for type 1 diabetes. Early career scientists have the opportunity to move forward with their research and contribute to the growing understanding of the disease and treatment options. Learn more and support these efforts by visiting http://diabetesresearchconnection.org.

Learn More +

Is Cannabis Use Safe for Individuals with Type 1 Diabetes?

Cannabis use has been a hot topic in recent years with more states legalizing recreational use in addition to medicinal use. Just like any drug, cannabis has its risks and benefits which can vary from person to person depending on their individual situation.

A recent study looked at how cannabis use may impact individuals with type 1 diabetes in regard to diabetic ketoacidosis (DKA). DKA occurs when the body does not make enough insulin and ketones build up in the bloodstream due to the breakdown of fats instead of sugars.

The study found that moderate cannabis users with type 1 diabetes are twice as likely to develop DKA than non-users. Researchers used data from 932 adults who participate in the T1D Exchange clinic registry (T1DX).

It is important for individuals with T1D to understand the risks associated with using cannabis and how it can potentially affect their overall health and well-being, especially in regard to diabetes management. DKA can develop very quickly and can be potentially fatal if left untreated.

Though not involved in this study, the Diabetes Research Connection (DRC) supports early career scientists in pursuing novel research studies to advance understanding of T1D as well as improve diagnosis, treatment, and prevention strategies. Learn more about current projects and how to support these efforts by visiting http://diabetesresearchconnection.org.

 

Learn More +

Controlling Beta Cell Proliferation and Apoptosis to Manage Type 1 Diabetes

A key indicator of type 1 diabetes is lack of insulin-producing beta cells in the pancreas. These cells are mistakenly attacked and destroyed by the immune system leaving individuals unable to naturally manage their blood sugar. With little to no production of insulin, the body cannot effectively process sugars and use them as fuel. Instead, individuals must constantly monitor their blood glucose levels and administer insulin as needed.

However, a recent study uncovered how an FDA-approved drug for treating breast cancer may also be effective in diabetes care. Neratinib is a dual inhibitor of HER2 and EGFR kinases, but researchers have also found that it is incredibly effective at blocking mammalian sterile 20-like kinase 1 (MST1) as well. MST1 plays a key role in regulating beta cell proliferation and apoptosis. By inhibiting MST1 expression, insulin-producing beta cells may be protected from this process leading to greater beta cell survival and improved function.

In addition, when mouse models and human islets were treated with neratinib, they showed a marked improvement in glucose control and maintained lower overall glucose levels. The drug also restored expression of specific transcription factors such as PDX1 that contribute to glucose metabolism and insulin production.

Neratinib is an FDA-approved cancer treatment drug currently being used for breast cancer, but its effectiveness in treating other forms of cancer is being explored as well. Now researchers are examining whether its indications could be expanded to include diabetes.  While it has been proven safe in cancer treatment, scientists are looking at ways to decrease its toxicity and improve specificity for diabetes.

In its current form, neratinib does not only target MST1 – it inhibits other kinases as well. Furthermore, there is concern that an extreme decrease in beta cell apoptosis could lead to increased expression of other cell types which could impact health. However, researchers can use this study as a foundation for exploring ways in which to refine the drug and improve beta-cell protection and function while minimizing other effects.

Diabetes Research Connection (DRC) is interested to see how this study impacts future treatment and prevention efforts in regard to type 1 diabetes. The DRC provides critical funding to early career scientists pursuing novel, peer-reviewed research projects focused on prevention, treatment, and improvement of quality of life for individuals living with the disease. This support can lead to scientific breakthroughs and have a significant impact on understanding of type 1 diabetes. To learn more about current projects and how to support these efforts, visit http://diabetesresearchconnection.org.

Learn More +

Leveraging the Power of Light to Manage Type 1 Diabetes

A common problem in managing type 1 diabetes is maintaining relatively stable blood glucose levels. By the time a person realizes their blood sugar is rising or falling and begins to treat it, they may already experience spikes. This can be tough on the body and lead to over- or undertreatment in an effort to curb the highs or lows. Though technology has made it faster and easier to track blood glucose levels and more accurately administer insulin, it’s still not a perfect system.

A recent study reveals that researchers may have come up with a way to manage blood sugar without manually administering insulin. They engineered pancreatic beta cells to be responsive to exposure to blue light. By introducing a photoactivatable adenylate cyclase (PAC) enzyme into the cells, they produce a molecule that increases insulin production in response to high levels of glucose in the blood.

The molecule is turned on or off by blue light and can generate two to three times the typical amount of insulin produced by cells. However, it does not boost production when glucose levels in the blood are low. Furthermore, the cells do not require more oxygen than normal cells, which helps alleviate the common issue of oxygen starvation in transplanted cells.

The study was conducted on diabetic mice, so more research is needed to determine whether the process will be as effective in humans. If it is, this could mean that individuals with type 1 diabetes may have an option for controlling blood sugar levels without pharmacological intervention. When paired with a continuous glucose monitor (CGM) or other device as well as a source of blue light, it could create a closed loop model of managing the disease by functioning as a bioartificial pancreas.

This could be potentially life changing for individuals living with type 1 diabetes, and Diabetes Research Connection (DRC) is excited to see how the study progresses. Though not involved with this project, the DRC supports advancement of type 1 diabetes research and treatment options by providing critical funding for early career scientists pursuing novel research projects. Learn more by visiting http://diabetesresearchconnection.org.

Learn More +

Improving Vascularization of Transplanted Islet Cells

One option that researchers have explored for treating type 1 diabetes is cell transplantation. By introducing new pancreatic islet cells, they aim to better control glucose levels and insulin production. However, there are still many challenges surrounding this approach including cell death due to poor vascularization.

Pancreatic islet cells are highly vascularized in order to quickly and easily transport insulin. If they are not able to establish blood vessel connections following transplantation, they cannot work as effectively and may not survive long-term. A recent study has found an improved method for promoting vascularization and enabling more effective cell transplantation.

A multidisciplinary team of researchers developed a biomimetic microvascular mesh that maintained its shape and promoted the survival of transplanted cells by stimulating revascularization. When transplanted into diabetic mouse models, they were able to maintain normoglycemia for up to three months.

The researchers created micropillars to improve anchoring of the microvascular mesh and decrease risk of shrinkage as cells matured. They had success using both human umbilical vein endothelial cells (HUVECs) and human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) in the meshes. Compared to a mesh without these cells, the mesh with the cells showed both anastomoses and vascular remodeling which are essential in vascularization during cell replacement therapy.

Though they have only been tested in mouse models, biomimetic microvascular mesh could one day be used to improve cell replacement therapy for humans with type 1 diabetes in order to improve glycemic control. This study opens doors for additional research and further refining islet transplantation methods.

Though not involved with this study, Diabetes Research Connection (DRC) supports novel research projects that strive to advance treatment for type 1 diabetes and one day find a cure. Early career scientists can receive up to $75K in funding from donations by individuals, corporations, and foundations to support their research. Learn more by visiting http://diabetesresearchconnection.org.

Learn More +

Expanding Type 1 Diabetes Research Through Marmoset Models

It is not uncommon for researchers to use animal models for initial research before transitioning to human clinical trials. Many animals’ systems are biologically similar in nature to humans and respond in similar ways to various diseases and medications. Often mouse models are used for diabetes research, but other species such as nonhuman primates (NHP) are also advantageous. While various types of monkeys and baboons have been used to study diabetes pathogenesis and treatment, there was previously not a marmoset model.

In a recent study, researchers successfully induced type 1 diabetes mellitus in marmosets. They conducted a partial pancreatectomy and administered streptozotocin (STZ) to decrease and destroy insulin-producing beta cells. This led to the marmosets having higher sustained blood glucose levels (above 200 mg/dL) and the inability to manage their condition through natural insulin production. Instead, they were injected with exogenous human insulin which brought their glucose levels back into the target range. Researchers found that they had a high sensitivity to human insulin making them a valuable NHP model.

Multiple glucose and insulin tolerance tests were conducted to determine how the diabetic marmosets responded compared to normal marmosets and whether they would be suitable candidates for future testing regarding islet transplantation. Continuous glucose monitors (CGM) were used to compare normal marmosets with diabetic marmosets as well, further showing that diabetic marmosets had consistently higher blood glucose levels, especially following meals, much like humans with type 1 diabetes.

While additional research is necessary, researchers believe that marmoset models could play an integral role in type 1 diabetes research and the advancement of preclinical testing. They were able to effectively induce diabetes in the marmosets and control it using human insulin, so the next step would be to move to cell transplantation trials. Eventually these transplant models may translate to human clinical trials and enhance diabetes treatment options.

It is these types of studies and use of animal models that help to advance scientists’ understanding and treatment of type 1 diabetes and allow them to work toward a cure. Diabetes Research Connection (DRC) is interested to see how marmoset models will influence the future of diabetes care.

DRC is committed to supporting early career scientists in pursuing novel, peer-reviewed research regarding type 1 diabetes. Researchers can receive up to $75K in funding for their projects allowing them to move forward with their work. Learn more about current projects and how to help by visiting http://diabetesresearchconnection.org.

Learn More +

Exploring the Use of Targeted Proteins in Managing Type 1 Diabetes

Currently, the most effective treatment for type 1 diabetes is the administration of insulin, but this is not a perfect solution. Since the body is unable to produce enough – or in some cases any – insulin on its own, individuals are tasked with carefully determining when and how much they need to keep blood sugar levels in check. This in itself can be challenging, and too much or too little insulin can lead to potentially life-threatening hyper- or hypoglycemia.

In addition to controlling blood sugar, insulin also helps regulate ketones within the blood. Ketones are created when lipids are broken down by the liver because the body is lacking glucose. Increased ketone levels can lead to diabetic ketoacidosis. Trouble controlling fat in the blood can put individuals at a greater risk for cardiovascular problems.

However, a recent study by researchers at the University of Geneva in Switzerland reveals that combining insulin with high doses of the protein S100A9 may improve regulation of glucose as well as lipids. Though it has only been tested in insulin-deficient diabetic mice thus far, the researchers are in the process of gaining approval for phase I human clinical trials. Other studies have already shown that there is a reduced risk of diabetes in individuals with higher levels of S100A9, so they are hopeful that this protein can play an integral role in diabetes management as well.

Another interesting discovery that the researchers made was that S100A9 was only effective when cells with TLR4 receptors were present as well. At this point, they are unsure exactly what the relationship is and why TLR4 is necessary for the process to work. However, their study leads the way toward reducing the amount of insulin necessary to effectively control blood glucose and ketone levels by combining it with the S100A9 protein.

Though not involved in this study, Diabetes Research Connection (DRC) is excited to see how it progresses once human clinical trials begin as it has the potential to impact treatment for millions of people living with type 1 diabetes. The DRC supports the advancement of research and treatment through providing critical funding to early career scientists pursuing novel research studies for the disease. Find out how to support these efforts and learn more about current projects by visiting http://drcnew.awp.uxtesting.net.

Learn More +

Islet Transplantation May Have Long-Term Benefits for Type 1 Diabetes.

Islet transplantation is not a new concept, but it is one that scientists are continually trying to refine and improve. A major challenge with this procedure is rejection or destruction of the transplanted cells. However, researchers followed up with a group of 28 patients who had undergone islet transplantation and found that 10 years later, there were still lasting benefits.

A recent study looked on how patients fared a decade after receiving transplants. Fourteen of the patients received only an islet transplant, while the other 14 had a kidney graft in addition to the islet transplant. Regardless of procedure, researchers found that “28% remained completely independent of exogenous insulin” after 10 years, a slight decrease from the 39% who were independent of insulin use after five years. However, even those participants who did return to needing insulin had improved glycemic control and a lower exogenous insulin requirement than prior to transplantation. In addition, they had fewer severe hypoglycemic events.

A major factor in the effectiveness of the transplant was graft function. Those individuals who had optimal graft function maintained insulin independence longer than those who had poorer graft function. Immunosuppression was used to help support graft survival, but there were some serious adverse events as a result. In the 28 participants, there were eight instances of infections or skin carcinomas and 11 diabetes-related events that were cardiovascular.

Five participants experienced symptomatic cardiovascular events and six experienced asymptomatic myocardial ischemia. One person died of a stroke. However, researchers report that “mortality rate in patients similar to those in the current study but who did not undergo islet transplantation is three to four times higher with causes of death largely being severe hypoglycemia or ischemic heart disease.”

It is encouraging to see that a decade after islet transplantation, participants are still experiencing positive outcomes in regarding to diabetes management, with some maintaining insulin independence. As researchers continue to learn more and are able to refine and improve islet transplantation, more patients may benefit long-term from this treatment option and potentially achieve insulin independence.

Diabetes Research Connection (DRC) stays abreast of the latest findings in the field and provides critical funding for early career scientists to pursue research related to type 1 diabetes. It is through this work that improved treatments become available and scientists enhance their understanding of the disease. Learn more about these efforts and how to support existing projects by visiting http://drcnew.awp.uxtesting.net.

Learn More +

Could Closed-Loop Systems Improve Blood Glucose Management?

One of the latest technologies being tested for managing type 1 diabetes is a closed-loop system. This system uses a continuous glucose monitor (CGM) to measure blood glucose levels. When blood sugar begins to rise outside of the target range, it sends information to an insulin pump to automatically administer insulin. When blood sugar begins to fall, insulin is not administered. It is a closed loop because the patient is not deciding when to inject insulin or how much, but rather the system does so automatically.

A recent study involving 168 individuals with type 1 diabetes between the ages of 14 and 71 were part of a six-month trial using a closed-loop system. One hundred and twelve people were randomly assigned to the closed-loop group while the remaining 56 people used a sensor-augmented pump and were considered the control group. All 168 participants completed the trial. There were no incidences of hypoglycemia and only one incidence of diabetic ketoacidosis, which occurred in the closed-loop group.

The results showed that the closed-loop group remained in the target range for glucose levels (70-180 mg/dL) a greater percentage of time than those in the control group. On average, their time in the target range increased from 61% to 71%, while the control group remained around 59%. In addition, the closed-loop group spent less time with glucose levels above 180 mg/dL or below 70 mg/dL. Throughout the duration of the six-month trial, participants in the closed loop group remained in closed-loop mode (with the system automatically managing glucose monitoring and insulin administration) a median of 90% of the time.

While the closed-loop system is not perfect, these findings show that it improved time spent in the target glucose range, which is desirable in diabetes management. It also reduces the manual tracking and input from individuals with type 1 diabetes in managing the disease. While more research and testing are needed, it is a step in the right direction toward developing what many refer to as an “artificial pancreas.”

Diabetes Research Connection (DRC) is interested to see how this system will continue to advance and improve diabetes management in the future and continues to follow its progress.  These types of devices play an integral role in supporting individuals with T1D and helping them to maintain more normal blood glucose levels. The DRC supports early career scientists in pursing novel research studies geared toward improving understanding, diagnosis, and treatment of T1D with the goal of one day finding a cure. Learn more about these efforts and how to help by visiting http://diabetesresearchconnection.org.

Learn More +

Improved Transplantation of Islet Organoids May Support Type 1 Diabetes Treatment

One approach to treating type 1 diabetes is transplanting insulin-producing beta cells into the body, or cells that can develop to perform this function. However, there are still many challenges in getting the body to accept these cells without extensive immunosuppression. Even still, the cells often have a limited survival rate.

In a recent study, scientists examined the potential of creating insulin-producing organoids to regulate blood sugar and treat type 1 diabetes. They combined dissociated islet cells (ICs) with human amniotic epithelial cells (hAECs) to form islet organoids, or mini pancreas-like organs. These organoids, which can contain multiple types of cells and cell functions, were transplanted into the portal vein because the area is easily accessible and has a low morbidity rate.

In similar approaches, researchers have been faced with cell death due to poor revascularization of the transplanted cells as well as inflammation. However, in this study, they found that by introducing hAECs, they were able to curb some of these effects. hAECs not only secrete proangiogenic growth factors, but anti-inflammatory growth factors as well including insulin-like growth factors and associated binding proteins. Furthermore, they produce high levels of hyaluronic acid which suppresses tumor growth factor β and stimulates VEGF-A production which supports improved revascularization. They also found that hAECs improved protection of IC-hAEC organoids against hypoxic stress thereby reducing risk of cell death.

Results showed that 96% of diabetic mice who received IC-hAEC organoid transplants achieved normoglycemia within one month. The median rate for this process to occur was 5.1 days. In addition, at one-month post-transplant, the mice showed similar glucose clearance as non-diabetic mice.

While this study has only been performed on mouse models so far, the goal is to achieve similar results in human trials. Additional research and testing are needed to determine if the process is translatable. This approach has the potential to improve management of type 1 diabetes and could lead to a possible cure for the disease if results are sustainable in the long-term.

Though not involved in this study, Diabetes Research Connection (DRC) supports advancements in type 1 diabetes research and treatment by providing critical funding to early career scientists. It is these types of studies that assist in transforming the future of diabetes care. Learn more and support these efforts by visiting http://diabetesresearchconnection.org.

Learn More +

Rotavirus Vaccine May Reduce Risk of Type 1 Diabetes

There is no single factor that is entirely responsible for the development of type 1 diabetes. Scientists believe that both genetic and environmental factors play a role. One area that they are examining more closely is the impact of enteroviruses. Studies have found that since the introduction of two rotavirus vaccines in 2006 and 2008, the incidence of type 1 diabetes in children has decreased.

A recent study compared data from 2001 to 2017 for nearly 1.5 million infants in the United States. They looked at the incidence rate of type 1 diabetes in those who received the full series of either rotavirus vaccine (pentavalent RotaTeq or monovalent Rotarix), those who received only partial vaccination, and those who were unvaccinated either by parental choice or because the vaccinations had not yet been developed. They also looked at incidence rates among children who received both a rotavirus vaccine and the diphtheria, tetanus, and pertussis (DTaP) vaccines at the same time, and those who received only the DTaP vaccines.

While partial vaccination had no impact on risk of type 1 diabetes, infants who completed the rotavirus vaccine series showed a 33% reduction in risk, with those receiving the pentavalent vaccine experiencing a 37% lower risk. In addition, children who were vaccinated had lower hospital admission rates due to enteroviruses within 60 days of being vaccinated than children who were unvaccinated. According to the study, in terms of type 1 diabetes risk, “Overall, there was a 3.4% decrease in incidence annually in children ages 0-4 in the United States from 2001-2017, which coincides with the vaccine introduction in 2006.”

When the rotavirus and DTaP vaccines were administered together, there was a 56% reduction in risk of developing type 1 diabetes than when DTaP vaccines only were given. This leads scientists to believe that the rotavirus vaccine plays an integral role in risk reduction. While it does not entirely prevent infants from developing type 1 diabetes at some point in their life, it may reduce their risk of the disease.

Previous studies have shown that rotavirus infection may increase the destruction of insulin-producing beta cells in diabetes-prone mice. In addition, children who had multiple rotavirus infections had increased islet antibody levels which may contribute to islet autoimmunity, which in turn is linked to type 1 diabetes risk.

Though more research is necessary including longer longitudinal studies to determine if type 1 diabetes was prevented entirely or only delayed, this study is a step in the right direction toward potentially reducing diabetes risk. Encouraging families to get their children the rotavirus vaccine – which is covered at no cost under most health insurance plans – could be an effective strategy in decreasing risk of type 1 diabetes.

Diabetes Research Connection (DRC) is interested to see how these findings may impact the future of prevention efforts for type 1 diabetes and what additional research will discover. The DRC supports early career scientists in pursing novel research regarding type 1 diabetes including diagnosis, prevention, treatment, and management of the disease. To learn more about current projects and how to support these efforts, visit http://diabetesresearchconnection.org.

Learn More +

Exploring C-Peptide Persistence in Type 1 Diabetes

In diagnosing diabetes, be it type 1 or type 2, one of the key factors doctors look for is C-peptide levels. Traditionally, scientists have believed that low C-peptide levels indicated type 1 diabetes as the body is unable to produce an adequate supply (if any) of insulin, while higher C-peptide levels were associated with type 2 diabetes as the body made insulin but was unable to effectively use it.

However, a recent study shows that this may not be entirely accurate. In a large cohort study in Scotland, there was a broad range of variability in C-peptide persistence across individuals of different ages and duration of disease. Individuals who were older when diagnosed and were close to age of diagnosis had higher C-peptide levels than those who were adolescents when diagnosed and had been living with the disease for a longer period of time. Scientists believe this may point toward there being multiple genetic networks that impact diabetes risk.

The findings also showed that similar C-peptide levels may be present in individuals with adult-onset type 1 diabetes who did not immediately require insulin treatment as those who were diagnosed with type 2 diabetes. Many people with higher C-peptide levels also have increased amounts of proinsulin, which is a prohormone precursor to insulin. However, the cells do not respond to primary stimuli which could mean that they are in a stunned state. If this is the case, there is a potential that they could recover and once again play an active role in insulin production.

The ratio of proinsulin to C-peptide may also be influenced by genetic risk of diabetes. Both genetics and environmental factors may come into play regarding damage to beta cells and their ability or inability to produce insulin.

This study challenges previous understanding about the differences in type 1 and type 2 diabetes when it comes to diagnosis and treatment. There may be the potential to stimulate pancreatic beta cell function in individuals with type 1 diabetes depending on their levels of proinsulin, insulin, and C-peptide.

Diabetes Research Connection (DRC) is interested to see how this may impact the future of diagnosis and treatment of diabetes. It could certainly lead the way to more in-depth research opportunities, and the DRC provides critical funding to support these types of initiatives. Early career scientists can receive up to $75K from the DRC to pursue novel research projects focused on type 1 diabetes. To learn more, visit http://diabetesresearchconnection.org.

Learn More +

Could Improving Cell-to-Cell Communication Enhance Cell Replacement Therapy Options for Type 1 Diabetes?

Researchers have been exploring the potential of stem cell therapies for years, however this is a very challenging endeavor because there are many factors that influence cell development, differentiation, and fate. In the case of type 1 diabetes, researchers have been studying methods for preventing the destruction of insulin-producing beta cells, stimulating the generation of new cells, and directing differentiation of stem cells among other strategies.

In a recent study, scientists focused on enhancing cell-to-cell communication in order to influence differentiation of embryonic stem cells. They examined the role of Connexin 43 (Cx43) specifically, which is a gap junction (GJ) channel protein. Scientists found that by using the AAP10 peptide to activate Cx43 GJ channels, they could steer differentiation of cells toward definitive endoderm and primitive gut tube lineages. In turn, with improved communication between cells triggered by the AAP10 peptide, definitive endoderm cells were more likely to become pancreatic progenitors and pancreatic endocrine progenitors.

Pancreatic progenitors (PP) and pancreatic endocrine progenitors (PE) play a role in the development of pancreatic islet cells which produce insulin and glucagon. These are the same cells that the body mistakenly attacks and destroys in individuals with type 1 diabetes. The ability to influence the differentiation of human embryonic stem cells into PPs and PEs may support improved cell replacement therapies for diabetes.

There is still a great deal of research to be done as it is difficult to manipulate the mechanisms of cell communication in order to produce desired results. Scientists are also continuing to investigate whether improved intercellular communication could lead to an increased production of pancreatic islet cells.

Researchers involved in this study include Dr. Wendy Yang, Dr. Laura Crisa, and Dr. Vincenzo Cirulli. Yang’s research is funded by Diabetes Research Connection (DRC) and Crisa and Cirulli are part of the DRC’s scientific review committee. To learn more about the DRC and the funding it provides to support type 1 diabetes research, visit http://diabetesresearchconnection.org.

Learn More +

Antibody-Drug Conjugate May Help Reduce Allograft Rejection.

Cell transplantation has been an area of focus in developing treatment for type 1 diabetes. Many studies have examined both autologous and allogeneic transplants and the benefits and risks they provide. A major challenge continues to be rejection and the body’s destruction of these cells, whether initially derived from its own cells or not.

However, a recent study found that an anti-CD103 antibody-drug conjugate (M290-MC-MMAF) may reduce pancreatic islet allograft rejection in mice. This drug decreased the amount of CD103+CD8+ effector T cells while at the same time increasing the amount of CD4+CD25+ regulatory T cells. This balance led to improved survival rate of the allograft and supported immunosuppression without causing systemic toxicity. When CD103+CD8+ levels were increased, allograft rejection quickly followed.

While this study has only been conducted in mouse models, it shows potential for pancreatic islet allografts in treating type 1 diabetes. Further research is necessary to determine how this process translates to human cells. M290-MC-MMAF could eventually be used as a therapeutic intervention to reduce risk of allograft rejection in humans.

Diabetes Research Connection (DRC), though not involved in this study, stays abreast of the latest discoveries in the field and supports early career scientists in pursuing novel, peer-reviewed research projects related to type 1 diabetes. Scientists receive funding that is critical to conducting research and improving the diagnosis, treatment, and management of the disease and one day finding a cure. To learn more about current projects and how to support these efforts, visit http://diabetesresearchconnection.org.

Learn More +

Early Biomarker for Pancreatic Beta Cell Loss Related to Type 1 Diabetes Identified.

For years, researchers have known that pancreatic beta cell death plays a major role in the development of type 1 diabetes. They have been striving to detect this process early on in order to better assess risk for the disease and develop potential treatments to stop progression. When the body destroys insulin-producing beta cells, it is no longer able to effectively manage blood glucose levels resulting in type 1 diabetes (T1D), a condition that currently has no cure.

In a recent study, researchers used diabetic mice and serum samples from individuals with various stages of T1D as well as INS-1 cells and human islets “to detect an early biomarker of T1D-associated beta-cells loss in humans.” The enriched microRNA (miR-204) that they discovered is released by beta cells during cell death and is detectable in human serum. However, it is only present in elevated levels in individuals with T1D and those who are autoantibody positive, not in individuals with type 2 diabetes.

This discovery may play a role in improving early detection of pancreatic beta cell death prior to full onset of T1D. In turn, that may open doors to new research and developments in treatment in order to reduce risk of T1D.

Diabetes Research Connection (DRC) is excited to see what this discovery could mean for the future of T1D diagnoses and prevention efforts. The DRC supports early career scientists in pursuing novel, peer-reviewed research projects focused on the diagnosis, prevention, treatment, and eventual cure of type 1 diabetes. Learn more about current projects and how to support these efforts by visiting http://diabetesresearchconnection.org.

Learn More +

Could Gluten Impact HbA1c Levels?

Researchers know that type 1 diabetes involves the body’s immune system mistakenly attacking and destroying insulin-producing beta cells, and that this can be affected by autoantibodies and antibodies. However, the body produces antibodies in response to many diseases, including celiac disease.

In a recent study, researchers explored the relationship between patients with celiac disease achieving antibody-negativity versus staying antibody-positive and the potential impact on type 1 diabetes. When individuals with celiac disease stop eating gluten, the body stops producing specific antibodies that react to gluten. Tight management of the disease may produce antibody-negative results during testing. If the person continues to eat some gluten, they will remain antibody-positive.

Scientists compared 608 pediatric patients with type 1 diabetes (T1D) and biopsy-proven celiac disease with 26,833 patients with T1D only. They found that those patients with both diseases who remained antibody-negative had lower HbA1c levels than those who were antibody-positive. The study also showed that, compared to patients with only T1D, those who had both celiac disease and T1D and were antibody-negative had lower total cholesterol, LDL-cholesterol, and frequency of dyslipidemia as well.

Though more research is necessary, achieving constant antibody-negative status may be associated with improved metabolic control and growth and have an impact on HbA1c levels. This could lead the way to advancements in treatment options for individuals with celiac disease and type 1 diabetes and perhaps type 1 diabetes alone as well.

Diabetes Research Connection (DRC) stays abreast of the latest developments in the field and supports early career scientists in pursuing peer-reviewed, novel research studies on type 1 diabetes. It is through these types of projects that researchers learn more about diagnosis, treatment, and prevention of this disease and move closer toward finding a cure. Learn more about current projects and how to support these efforts by visiting http://diabetesresearchconnection.org.

Learn More +

Evaluating the Effect of Specific T Cells on Type 1 Diabetes Risk and Treatment

As researchers delve more deeply into trying to understand the origins of type 1 diabetes (T1D), they become increasingly aware that there is not a single disease pathogenesis, but rather multiple paths that vary from person to person. While they know that T1D results from the immune system attacking and destroying insulin-producing beta cells in the pancreas, there may be several different factors that contribute to this risk.

A recent study examined a variety of T cells, T cell receptors, antigens, and autoantibodies that may play a role in the development of T1D. One common factor they found was that individuals with an elevated level of islet autoantibodies in the peripheral blood are at increased risk of developing T1D within their lifetime. Researchers also know that in addition to risk genes, human leukocyte antigen (HLA) genes and the autoantibody glutamic acid decarboxylase (GAD) could vary from person to person and impact the effectiveness of targeted therapies. Children who possess two or more islet autoantibodies have around an “85% chance of developing T1D within 15 years and nearly a 100% lifetime risk for disease development.”

However, the mere presence of islet autoantibodies does not demonstrate disease state, because it could be years before clinical T1D presentation. In its early stage (stage 1), while the autoantibodies are present, beta cell function remains normal. As risk for T1D advances (stage 2), metabolic abnormalities develop. Finally, with T1D onset (stage 3), there is both a presence of autoantibodies and loss of beta cell function in regard to blood glucose. The staging paradigm was derived from data from the United States’ Diabetes AutoImmunity Study in the Young (DAISY), Finland’s Type 1 Diabetes Prediction and Prevention Study (DIPP), and Germany’s BABYDIAB studies.

Given the similarities of mouse models and human models when it comes to diabetes, mouse models are often used to study disease risk, evaluate pathogenesis, and assess potential treatment options. Researchers have found that specific antigens and T cells affect pancreatic islets differently. Understanding these antigen subsets could be critical in determining effective clinical therapeutics for prevention and treatment.

Thanks to the Network for Pancreatic Organ Donors (nPOD), more than 150 cases have been collected from organ donors with T1D since 2007, as well as more than 150 from non-diabetic donors and dozens of donors with autoantibodies but no clinical diabetes. These tissue donations have provided researchers with islets, cells, and data from multiple facets of the ody that contribute to T1D risk.

Understanding tissue specific T cells, antigens, and autoantibodies may help identify biomarkers of disease activity which could improve targeted therapeutic interventions. Eventually, this may help reduce risk of T1D by creating early intervention strategies.

While not involved with this study, Diabetes Research Connection (DRC) is focused on advancing understanding of T1D and improving prevention, diagnosis, and treatment options as well as progress toward a cure. Early career scientists receive critical funding to pursue novel, peer-reviewed research projects regarding multiple aspects of T1D. Learn more by visiting http://diabetesresearchconnection.org.

Learn More +

Examining the Impact of Intensive Glucose-Lowering Treatment on Hypoglycemia Risk

One of the key indicators in effective diabetes management is HbA1c level. In healthy, non-diabetic adults, the target range is 4% to 5.6%, while in individuals with diabetes, the goal is to maintain an HbA1c level of less than 7%. However, some treatment guidelines aim for achieving levels of 5.6% or less, or between 5.7% and 6.4%.

Striving for these lower HbA1c levels through intensive glucose-lowering therapy may prove more risky than beneficial, though, especially for adults who are considered clinically complex, according to a recent study. These individuals may benefit from less intensive treatment and slightly higher target HbA1c levels to reduce risk of emergency department visits and hospitalizations for severe hypoglycemia.

The study included data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014, and “participants were categorized as clinically complex if 75 years or older or with 2 or more activities of daily living limitations, end-stage renal disease, or 3 or more chronic conditions.” They were considered to be engaged in intensive treatment if their HbA1c level was below 5.6% and they took any glucose-lowering medication, or if their HbA1c level was between 5.7% and 6.4% and they took two or more glucose-lowering medications.

In addition to NHANES data, other population-level studies were included as well when comparing data and outcomes. Overall, overtreatment was estimated to occur in up to 50% of non-clinically complex patients and up to 60% of clinically complex patients.

For the study, 662 nonpregnant adults who had diabetes and maintained HbA1c levels of less than 7.0% were used to represent around 10.7 million adults with diabetes in the United States. Of these participants, 20.1% were age 75 or older, 21.5% were treated intensively, and 32.3% were considered clinically complex. The researchers estimated that over two years, there would be 31,511 hospitalizations and 30,954 emergency department visits for severe hypoglycemia, and that around 4,774 hospitalizations and 4,804 ED visits could be directly attributed to intensive glucose-lowering therapies.

The study found that aggressive treatment of diabetes to achieve lower HbA1c levels could actually have a negative effect on overall health, especially for clinically complex patients who experienced severe hypoglycemic events. It is recommended that many elderly and clinically complex patients avoid intensive treatments and follow relaxed glycemic targets. Recommended HbA1c levels should be evaluated on an individual basis and take into account patient health, comorbidities, and clinical complexity.

There were limitations to this study, and researchers note that “true numbers are likely to much higher” regarding hypoglycemic events and the number that are directly attributable to intensive glucose-lowering therapy.

Type 1 diabetes management is a complex process, and researchers are continually advancing their understanding of the disease and effective treatment options. Diabetes Research Connection (DRC) follows advancements in the field and potential impact on individuals living with T1D.

DRC supports novel, peer-reviewed research studies regarding the diagnosis, treatment, and quality of life for those living with the disease. Learn more about current projects and how to donate to these efforts by visiting http://diabetesresearchconnection.org.

Learn More +

Could Peripheral T Helper Cells Be Linked to Type 1 Diabetes Risk?

Type 1 diabetes (T1D) is a complex disease. Researchers believe that both genetics and autoantibodies play a role in development of the disease. In individuals with T1D, the immune system mistakenly attacks and destroys insulin-producing beta cells in the pancreas. A new study has found that peripheral T helper cells may play a role in initiating this process.

The study showed that children with T1D, as well as those who were autoantibody-positive who developed the disease later on, both had an increase in the amount of peripheral T helper cells circulating in their blood. Researchers believe that much like follicular helper T cells, peripheral T helper cells may also be involved in activating B cells which target against proteins in pancreatic islet cells and contribute to the development of T1D.

The ability to identify children who are at increased risk for the disease due to genetics as well as the elevated presence of peripheral T helper cells may improve options for proactively monitoring and treating T1D. It could also support the development of new immunotherapies for the disease.

More research is necessary to better understand the role of this T-cell subset and how it impacts type 1 diabetes risk and development of the disease as well as how it could improve treatment or prevention options. Though not involved with this study, Diabetes Research Connection (DRC) follows the latest developments and advancements regarding type 1 diabetes understanding, treatment, and prevention.

DRC provides critical funding for early career scientists pursuing novel research studies related to the disease and hopes to one day find a cure. To learn more about current projects or how to help, visit http://diabetesresearchconnection.org.

Learn More +

Does Timing of Exercise Affect Blood Glucose Levels for Individuals with Type 1 Diabetes?

Regular exercise is an important part of maintaining good health, and this goes for individuals with type 1 diabetes (T1D) as well. However, the question has often risen as to whether the time of day that individuals engage in exercise has an impact on their blood sugar management. A recent study compared results when resistance training was completed in the morning during a fasting state versus in the afternoon after blood sugar had been managed throughout the day.

The randomized study involved 12 participants between the ages of 18 and 50 who had been diagnosed with T1D for a least a year, did not take any medications (aside from insulin) that may impact their blood glucose levels, had no limitations on required exercises, and did not perform shift work. They were asked to keep a log of their food intake and insulin dosage because they were blinded to continuous glucose monitoring.

The results showed that engaging in resistance exercise in the morning (7 a.m.) led to a higher risk of hyperglycemic episodes than exercising in the afternoon (5 p.m.). Blood glucose levels tended to be higher during morning exercise and the 60-minute recovery period as well as during the next six hours. However, with afternoon exercise, blood glucose levels declined during exercise and returned almost to baseline during recovery. There was also less glycemic variability during the six hours post exercise.

It is essential that individuals with type 1 diabetes talk to their doctor before starting or changing their exercise routine, and that they carefully monitor their blood glucose before and after physical activity. Studies like these play an important role in helping individuals with T1D to better manage the disease and improve their quality of life.

Diabetes Research Connection (DRC) stays abreast of the latest developments in the field and supports early career scientists in pursuing novel, peer-reviewed research projects focused on prevention, treatment, and an eventual cure for T1D as well as improvement of quality of life. Learn more about current studies and how to support these efforts by visiting http://diabetesresearchconnection.org.

Learn More +

Exploring the Potential Impact of Genetics and Infection on T1D Risk

There is no clear, concise explanation for why some people develop type 1 diabetes (T1D) and others do not, or what puts some people at greater risk for the disease. The origins and triggering factors for T1D are something that scientists have been studying for decades. A recent study looks at the possible relationship between genetic risk variants and viral infections and their impact on T1D development.

In some individuals, enteroviruses may trigger or accelerate disease development. However, in others, these same viruses may stimulate a variety of protective factors. Both genetic and environmental factors come into play, and researchers are exploring how to use these findings to improve treatment and prevention of T1D.

Scientists know that the destruction of insulin-producing beta cells plays a role in disease development. Some individuals present with autoantibodies long before T1D develops, and there are still beta cells present in many people even after living with the disease for many years. Yet they are still unsure about exactly what triggers beta cell destruction.

Studies have shown that around 50 percent of T1D risk is heritable. But just because a person carries this risk, does not necessarily mean they will develop the disease. There are around 60 different loci for single-nucleotide polymorphisms (SNP) that are associated with T1D and may contribute to risk.

Researchers believe that enteroviruses may also play a role. Many links have been found between enterovirus infections and the presence of various autoantibodies.  These infections may trigger beta cell autoimmunity in individuals who already have factors that put them at greater risk of developing T1D. By more effectively identifying individuals who have multiple risk factors, scientists may be able to create targeted antiviral treatments or preventive virus vaccines.

There is still a great deal of research to be done regarding the development of and triggers for T1D. Genetics, environment, and infection may all play a role, but their impact differs from person to person. There is also limited insight into factors such as ethnicity and gender, especially when looking at enteroviral etiology.

Though not involved with this study, the Diabetes Research Connection (DRC) contributes to current bodies of research through providing critical funding for early career scientists pursuing projects related to the diagnosis, prevention, treatment, and eventual cure for T1D. Scientists are learning more about the disease every day. Support these efforts by visiting http://diabetesresearchconnection.org.

Learn More +

Asthma Medication May Help Treat Diabetic Retinopathy

A common complication associated with diabetes (T1D) is diabetic retinopathy. Poor blood sugar control can increase risk of this disease because it impacts the blood flow to the eye by blocking and damaging tiny blood vessels. It can eventually lead to blindness. Symptoms can be very mild and barely noticeable at first, so this is often a condition that is treated in later stages when the effects become more severe.

However, a recent study found that the administration of an FDA-approved asthma medication – montelukast, also known as Singulair – may help reduce damage to blood vessels and nerves in and around the eye. This indication has only been tested in mouse models so far, but because it is already an FDA-approved medication for use in children and adolescents, this may decrease the time it takes to shift into human clinical trials.

Researchers found that the medication suppresses inflammation enough to alter the signaling of inflammatory molecules and prevent pathology, but not enough to compromise the body’s innate immunity. If found effective in human trials, it could be used as a prevention method as well as to treat diabetic retinopathy in its early stages. This could be beneficial to children who are newly diagnosed with type 1 diabetes and even those who have been managing the disease for several years and are at risk for eye disease.

Though not involved with this study, the Diabetes Research Connection (DRC) is interested to see how it progresses and what findings show when used in human subjects. It is encouraging to see a potential new option for reducing risk of diabetic retinopathy and improving quality of life for individuals living with type 1 diabetes.

DRC supports early career scientists in pursuing novel, peer-reviewed research studies aimed at prevention, treatment, and an eventual cure for type 1 diabetes. To learn more about current projects and how to help, visit http://diabetesresearchconnection.org.

Learn More +

Structured Mealtime Routines May Help Manage HbA1c Levels in Young Children with Type 1 Diabetes

Managing type 1 diabetes (T1D) can be challenging for anyone, but it can be especially difficult for parents of young children with the disease. They must carefully monitor their child’s diet and activity while regularly checking blood glucose levels. A recent study has found that those children who receive preprandial insulin and eat on a regular schedule tend to have improved HbA1c levels.

Researchers analyzed data from 22 Australian children age seven or younger. Their parents tracked the exact amounts and types of food and beverages offered and consumed by their children over a three-day period. They also answered 16 questions regarding mealtime routines and their child’s eating patterns, such as whether they grazed throughout the day or had set snack times and meal times. In addition, it asked about use of preprandial insulin.

The study found that 95% of children used preprandial insulin, and all children ate at least three meals per day. For 81% of children, their parent determined when they were offered food, but the other 19% followed child-led eating patterns. While there was no direct correlation between carbohydrate, protein, or fat intake on HbA1c, researchers did note that HbA1c levels were lower in those children who ate at regular mealtimes as opposed to grazing throughout the day.

Another interesting note was that the children with T1D ate similar diets as those children without the disease. Furthermore, none of the children in the study met the daily recommended vegetable intake, and only 28% ate recommended amounts of lean meats and protein. Additional research is necessary to evaluate the impact of diet quality on diabetes management.

It is these types of studies that provide further insight into improving management of type 1 diabetes. The Diabetes Research Connection (DRC) provides early career scientists with up to $75K in funding to support peer-reviewed, novel research studies focused on prevention, treatment, and management of type 1 diabetes as well as working toward a cure. To learn more and donate to current projects, visit http://diabetesresearchconnection.org.

Learn More +

Nasal Glucagon Approved to Treat Severe Hypoglycemia

If you or someone you love is living with type 1 diabetes, you know that, in addition to blood sugar becoming too high, having it drop too low is a serious concern as well. When blood sugar falls below 70mg/dL, individuals often start feeling the effects such as shakiness, sweating, chills, lightheadedness, weakness, blurry vision, or tiredness.

If blood sugar continues to drop, it can lead to severe hypoglycemia where the person may be unable to treat their low blood sugar themselves due to confusion, seizures, or loss of consciousness. When this occurs, the individual with T1D often relies on medical personnel or a trained bystander to administer glucagon. Traditionally, glucagon is injected into the arm, thigh, or buttock. However, the medication must first be reconstituted, which involves injecting the contents of the syringe into a vial, mixing it together, then drawing it back into the syringe to inject into the person. In an emergency situation, this can be a lot of steps to follow and there is plenty of room for error.

In an effort to simplify the process, Eli Lilly and Company has manufactured the first ever FDA-approved nasal glucagon, Baqsimi. The device is pre-loaded with 3 mg of glucagon and ready to use for patients age 4 and older. The medication stimulates the liver to release glucose and was found to effectively reverse insulin-induced hypoglycemia based on three studies encompassing more than 200 participants. There were no major safety concerns, and the potential adverse reactions were similar to those of injectable glucagon with the addition of watery eyes and nasal congestion. However, nasal glucagon is not recommended for individuals with pheochromocytoma or insulinoma.

Nasal glucagon provides yet another option for individuals with T1D to quickly – and more easily – treat episodes of severe hypoglycemia. It is simple to use because there is no reconstitution, multi-step processes, or injections necessary. The drug is expected to hit the U.S. market around the beginning of September 2019.

We are excited to see this new product come to market and is interested to see how it impacts diabetes care and management for individuals who experience severe hypoglycemia.

Learn More +

Researchers Identify a New Type of Diabetes

Many people are familiar with the two most common types of diabetes – type 1 diabetes and type 2 diabetes – but other forms exist such as gestational diabetes. According to a recent study, researchers have discovered another type as well: checkpoint inhibitor-associated autoimmune diabetes or CIADM.

Immune checkpoint inhibitors are often used in the treatment of advanced cancers to block programmed cell death-1 (PD-1) receptors. However, one of the potential adverse effects of anti-PD-1 therapy is CIADM. Patients who develop this condition experience a sudden loss of insulin as well as variable glycemic control and require insulin to manage the condition.

The retrospective cohort study included 538 patients who were treated for metastatic melanoma between March 2015 and March 2018. Patients had either received only anti-PD-1 therapy, a combination of anti-PD-1 and ipilimumab, or a combination of anti-PD-1 and either ipilimumab or a placebo. Of these 538 patients, six who received only anti-PD-1 and four who received anti-PD-1 and ipilimumab developed CIADM. Demographic information showed that 90 percent were male, the median age was 62, and only one patient had a prior history of diabetes. In addition, all 10 were negative for islet antigen 2 antibodies, insulin antibody, and zinc transporter 8 antibody.

These findings open doors for larger studies and more in-depth research into this condition, which is not the same as type 1 diabetes despite requiring insulin to manage blood glucose levels. The Diabetes Research Connection (DRC) is interested to see where this study will lead and what it may mean for the future of diabetes, treatment, and understanding of the disease.

The DRC provides essential funding for early career scientists focused on studying issues related to type 1 diabetes. These studies not only aim to advance understanding and improve diagnosis, treatment, and quality of life, but also to one day find a cure.

Learn More +

Could Hybrid Immune Cell Be Linked to Type 1 Diabetes?

Scientists understand a lot about the foundational cells that make up the body, but even still, they are always learning and discovering more. For instance, the body’s immune system is made of up B cells and T cells. These cells identify foreign invaders in the body – such as germs – and then attack and destroy them or create antibodies. In individuals with type 1 diabetes, these cells mistakenly destroy insulin-producing beta cells.

However, a recent study shows that scientists have discovered a hybrid cell that is a combination of both B cells and T cells. Not only does the surface of the cell have B cell and T cell receptors, it also expresses genes from both types of cells. In addition, these cells contain a unique genome sequence in B cell receptors that was only found in the cells of individuals with type 1 diabetes. Though some healthy individuals had this hybrid cell, they did not present with this specific B cell receptor sequence.

Upon further investigation, they found that this dual expresser cell binds very tightly to the HLA-DQ8 molecule, which is believed to play a major role in triggering the body’s attack on insulin-producing beta cells. Since this occurs in the early stages of type 1 diabetes development, researchers are interested in the potential for this discovery to one day support early diagnosis or prevention of the disease.

However, there are still many unanswered questions that exist. Scientists do not yet understand exactly how, why, when, or where the hybrid cells develop. While T cells originate in the thymus, B cells come from bone marrow and lymph nodes. Scientists are unclear where the overlap may occur that would combine these two distinct cells. They are also unsure why these dual expresser cells would go on to target insulin production.

This is the first time that this type of cell has been identified, so there is still a great deal of research that needs to be done. No one is exactly sure what this could mean for future understanding of type 1 diabetes and treatment options. That will come as more studies are done and more in-depth research is completed.

The Diabetes Research Connection (DRC) is excited to see where this discovery leads and the type of studies it generates. Though not involved with this study, the DRC provides critical funding to early career scientists for novel research projects related to type 1 diabetes. This is an integral part of advancing understanding and treatment of the disease.

Learn More +

Exploring the Link Between Disturbed Eating and Type 1 Diabetes

 

Managing type 1 diabetes requires careful monitoring of food intake, activity, blood sugar, and insulin administration. Depending on what a person eats and when, it impacts their blood glucose levels. A recent study found that around one-third of individuals between the ages of 16 and 28 experience issues with disturbed eating behavior (DEB). Furthermore, many report restricting or omitting insulin.

The study evaluated the responses of 300 participants to the Diabetes Eating Problem Survey-Revised (DEPS-R) as well as to questions regarding diabetes distress, depressive symptoms, and self-management of the disease. They were divided into four groups based on their DEPS-R scores for baseline and then one year later. The groups were low DEB (65.7%), increasing DEB (8%), decreasing DEB (7.3%), and persistent DEB (19%).

While mean DEPS-R scores were stable from baseline to one year later, the scores were higher in females than in males – 16.53 and 15.57 in females versus 8.71 and 8.96 in males. All groups reported varying levels of insulin restriction and omission, but it did not differ significantly between males and females.

Individuals who fell into the persistent DEB group showed the highest levels of diabetes distress and depressive symptoms while those in the low DEB group showed the lowest levels.  The low DEB group also had the lowest HbA1c levels, while the persistent DEB group had the second highest. The study also found that “self-management decreased when DEB increased, and vice versa.” This could in turn lead to poorer glycemic control and increased health care costs.

The researchers found overall that DEB can occur at any age and any stage of the disease, but that evaluating adolescents and young adults for DEB and eating disorders may be beneficial in supporting better diabetes management and glycemic control.

The Diabetes Research Connection, though not involved with this study, supports early career scientists in conducting research aimed improving prevention and finding a cure for type 1 diabetes as well as minimizing complications and improving quality of life for individuals living with the disease. Through donations from individuals, corporations, and foundations, scientists can secure the critical funding they need to move forward with their research.

Learn More +

Could Type 1 Diabetes Slow Brain Development in Children?

Since type 1 diabetes occurs when the pancreas produces little to no insulin, it is often diagnosed in childhood when this deficiency become more apparent. The body is unable to naturally manage blood sugar levels since the immune system mistakenly attacks and destroys insulin-producing beta cells. This means that parents must take over this responsibility until children are able to effectively manage their condition on their own.

Many parents are hesitant to overtreat and end up allowing blood sugar levels to remain slightly elevated (hyperglycemia) rather than risk having them drop too low (hypoglycemia). Neither condition is desirable as they can both lead to health complications. The goal is to create a management plan that enables blood sugar levels to remain as normal as possible.

A recent study found that hyperglycemia in children with type 1 diabetes may actually slow brain development and impact brain structure, cognitive function, and sensory processing. The study followed 138 children with type 1 diabetes between the ages of four and seven. Participants had been living with diabetes for an average of 2.4 years. These children were compared to 67 age-matched controls without type 1 diabetes.

After approximately 4.5 years, researchers found that those children with type 1 diabetes had decrements in both full-scale and verbal IQ, which was associated with hyperglycemia and an average HbA1c of 8%. The target goal for children is an HbA1c of less than 7.5%.

However, a larger study found that although full-scale, verbal IQ, and vocabulary were lower in those with T1D, there was no significant difference in processing speed, memory, or learning scores compared to the control group. The brains of children with T1D seemed to compensate for areas where there were challenges, and executive function was similar between groups.

Nelly Mauras, MD, chief of the Division of Endocrinology, Diabetes, and Metabolism at Nemours Children’s Health System and part of the Diabetes Research in Children Network (DirecNet) noted, “We are not suggesting that these youngsters aren’t performing academically. So far, these differences have not translated into functional outcomes in performance, at least not yet.”

Researchers continue to follow these groups in order to gather more information and determine the impact over a longer duration of time. They are interested in learning more about whether advanced technology can make it easier to maintain near normal glucose levels and whether HbA1c guidelines should be lower than 7.5% for children with type 1 diabetes to minimize hyperglycemia.

The Diabetes Research Connection (DRC), though not involved with this study, will continue to follow study progress to see what future comparisons hold and how this may impact treatment options and guidelines for children with type 1 diabetes. Current results may stimulate new research opportunities and increase understanding of the greater impact of T1D on health and development. The DRC provides critical funding for early career scientists to pursue novel research projects related to type 1 diabetes.

Learn More +

Later Onset Type 1 Diabetes Often Misdiagnosed as Type 2

Type 1 diabetes used to be commonly known as juvenile diabetes because it was often diagnosed in childhood. In individuals with this disease, the body mistakenly attacks and destroys insulin-producing beta cells, and eventually the body is no longer able to generate enough insulin to support normal blood sugar levels. Therefore, individuals must monitor their own blood-glucose and inject themselves with insulin.

However, research has shown that around 42% of people with type 1 diabetes were diagnosed after age 30. A recent study found that some people are mistakenly diagnosed with type 2 diabetes instead due to the late onset of the disease as well as clinical and genetic characteristics. This can make it difficult to properly differentiate between the two conditions.

The study examined data from 583 participants diagnosed with diabetes after age 30 who are part of the Exeter Diabetes Alliance for Research in England (DARE). Their data was compared to 220 DARE participants with the same study criteria but who were diagnosed with type 1 diabetes before age 30.

The researchers wanted to know how many of those diagnosed after age 30 had severe endogenous insulin deficiency (meaning their body naturally produced little to no insulin on its own), whether diagnosed with type 1 or type 2 diabetes. Severe insulin deficiency is a classic sign of type 1 diabetes but C-peptide and other tests are not always conducted to check for this condition in adults age 30 or older. However, the study found that 21 percent of participants who were treated with insulin had this condition, and 38% of participants not treated with insulin at diagnosis had it.

Individuals who required rapid insulin within one year of diagnosis or who were treated with insulin within three years of diagnosis had a higher likelihood of severe endogenous insulin deficiency; 85% and 47% respectively. This means that they likely had type 1 diabetes rather than type 2, regardless of what their initial diagnosis was. Participants diagnosed after age 30 shared very similar clinical and biological characteristics with the younger cohort.

It is critical that physicians conduct necessary testing to differentiate type 1 from type 2 diabetes regardless of age of onset. There are often different protocols for treating each of these conditions, and individuals with type 1 diagnoses have greater access to necessary resources such as continuous glucose monitoring (CGM) devices, insulin-pump therapy, and targeted diabetes education.

With more awareness of the frequency of type 1 diabetes onset after age 30 and associated characteristics, hopefully medical providers will be better able to assess and accurately diagnose this condition more quickly to provide essential treatment.

The Diabetes Research Connection (DRC) strives to support early career scientists in pursuing novel research studies that focus on the prevention, diagnosis, and treatment of type 1 diabetes as well as improving quality of life for individuals living with this disease. Research is critical to one day finding a cure.

Learn More +

Is it Possible to Delay the Onset of Type 1 Diabetes?

Living with type 1 diabetes (T1D) is challenging. It requires constant monitoring and adjustment of one’s blood sugar. Since T1D is commonly diagnosed in childhood, it can put additional strain on parents who must carefully manage their child’s condition. However, a recent study reveals that scientists may have found a way to delay the onset of type 1 diabetes by two years or more.

An antibody drug developed by Jeffrey Bluestone, an immunologist at the University of California, San Francisco, helps to shut down activated T cells thereby reducing the body’s immune system attacks on insulin-producing beta cells. It is the destruction of these cells that triggers T1D. Bluestone partnered with Kevan Herold, an endocrinologist at Yale University, to begin researching the potential of this drug in delaying the development of diabetes.

They first experimented with the drug on mouse models who were at high risk of developing type 1 diabetes, and it was effective in staving off the disease in many of the mice. In 2000, they shifted their work to human trials. The key was figuring out exactly when to administer the drug. If they gave it too early, there was not enough T cell activation so there was not much to protect against. Too late and there was too much T cell activity to manage. They had to find the precise time when diabetes was on the verge of developing or had been newly diagnosed.

In a trial involving 12 patients, after one year, nine of the participants had maintained or increased their body’s natural insulin production. This meant that their body was better able to manage glucose levels on its own and required less insulin to be injected.

After some setbacks and skepticism, Bluestone, Herold, and their team arranged for another trial. This time, they included participants who were at a high risk of developing type 1 diabetes within five years. They recruited 76 participants, 44 of whom received the drug (now known as teplizumab), and 32 of whom received a placebo. The drug was administered via IV infusion over 14 consecutive days. The results showed that while individuals who received the placebo were diagnosed with diabetes after an average of two years, those who received teplizumab were diagnosed after an average of four years. In addition, 72% of placebo recipients developed diabetes after five years compared to only 43% who received the experimental drug.

There is still a great deal of research and clinical testing that must be done, but this is a step forward in delaying onset of type 1 diabetes and eventually perhaps preventing development of the disease all together in high-risk individuals. Even delaying the disease by two years as the current study showed is monumental in improving quality of life. It is two fewer years of daily disease management and potential complications.

This discovery could lead to a greater understanding of diabetes prevention or delaying disease progression. It could stimulate new research and studies from scientists as they seek to advance results. The Diabetes Research Connection, though not involved with this study, provides critical funding that allows early career scientists to move forward with novel research projects. There’s no telling exactly what impact their findings could have on the future of type 1 diabetes or when the next major breakthrough will occur.

Learn More +

Scientists Uncover New Insight into Autoimmune Response

Autoimmune diseases are challenging to treat because the immune system plays a critical role in keeping the body healthy. However, when this system is destroying its own cells even without the presence of an infection, it can be problematic and potentially life-threatening. Millions of people suffer from autoimmune diseases such as type 1 diabetes (T1D), lupus, and scleroderma, and treatment options—as well as their effectiveness—are limited.

However, researchers at the University of Leeds and the University of Pennsylvania have made a new discovery that could change treatment in the future. They found two proteins—BRISC and SHMT2—that together are responsible for controlling the body’s response to infection or what it deems foreign invaders.

The team is aiming to figure out a way to target these proteins and keep the immune system from attacking and destroying the body’s own cells. This could eventually generate a new class of drugs for treating autoimmune disorders, though this type of treatment is still a long way off as a wealth of research and testing still needs to be conducted regarding this process.

It is encouraging to see new developments occurring and progress being made toward better understanding autoimmune diseases such as type 1 diabetes. With advanced research, scientists can formulate improved treatment options and perhaps one day a cure.

The Diabetes Research Connection, though not involved with this study, is part of the effort toward improving prevention, treatment, and quality of life for individuals living with T1D. Through donations from individuals, corporations, and foundations, early career scientists are able to receive critical funding to support novel, peer-reviewed research projects.

Learn More +

Exploring Protective Factors Against Diabetic Kidney Disease

One of the complications that can stem from living with diabetes is the risk of developing diabetic kidney disease. The kidneys play a critical role in filtering waste and excess water out of the blood and sending it out of the body. Prolonged high blood sugar and/or blood pressure can damage the kidneys and prevent them from functioning effectively. Eventually, individuals may require dialysis or a kidney transplant if damage is too extensive.

However, a recent study from the Joslin Diabetes Center found that some people have biological protective factors that may be effective in reducing risk of diabetic kidney disease. Their bodies have certain enzymes that affect glucose metabolism and protect the kidneys. Researchers studied cohorts of individuals who have been living with type 1 or type 2 diabetes for more than 50 years with minimal or no complications. They are referred to as Joslin Medalists.

One key finding was that the Medalists had increased PKM2, an enzyme in the blood that protects against diabetic kidney disease. There were also other metabolites and proteins that appeared at higher levels as well in their plasma. An interesting discovery was that the presence of an amyloid precursor protein (APP)—which is known to signal increased risk of Alzheimer’s disease—may actually work as a protective factor against diabetic kidney disease.

Scientists need to conduct additional research to further understand these potential protective factors and how they can be used to improve diagnosis and treatment of diabetic kidney disease or diabetes in general. Diabetic kidney disease can be a potentially fatal complication, so the more researchers understand about how it develops and the biological protective factors that can decrease risk, the better they can support individuals living with diabetes and their health.

Though not involved with this study, the Diabetes Research Connection (DRC) stays abreast of the latest research regarding type 1 diabetes and ways to improve diagnosis, treatment, and quality of life for individuals with the disease. Through donations from individuals, corporations, and foundations, the DRC provides critical funding for early career scientists to pursue novel research studies and further understanding of type 1 diabetes.

 

Learn More +

Connect For A Cure: May 2019 Newsletter

We’re committed to keeping our community updated. Click on the link below to read more about what we’ve been up to and the impact we are making together. It takes a community to connect for a cure!

May 2019 Newsletter

Learn More +

Beta Cell Proliferation May Help Protect Against Type 1 Diabetes

In individuals with type 1 diabetes (T1D), the body’s immune system mistakenly attacks and destroys insulin-producing beta cells. For years, researchers have been looking at options for suppressing this immune system attack, as well as processes to replace beta cells or stimulate the body to produce more. A recent study by researchers at the Joslin Diabetes Center may have found a way to do both and increase protection against T1D.

Scientists found that by speeding up cell proliferation and flooding mouse models with beta cells, it stopped the immune system from destroying these cells. According to Dr. Rohit Kulkarni, HMS Professor of Medicine and Co-Section Head of Islet and Regenerative Biology at the Center, “We believe there are some alterations in the new beta cells where a number of cells being presented as autoantigens are reduced or diluted, and therefore, because of the slow presentation of the antigens, the number of autoreactive T cells are less pathogenic.” In addition, when these cells were transplanted into other mice, they appeared to have a greater resistance to stress, which could also help them to survive longer in adverse conditions.

Gaining a greater understanding of the role cell proliferation can play and determining when the ideal time to activate this process is could have a positive impact on improving protective factors against T1D. This process has not yet been tested in humans, and there would likely still be a need for some level of immune system suppression to manage lingering autoimmunity.

The Diabetes Research Connection (DRC) stays abreast of the latest developments regarding T1D and is interested to see how these findings impact future studies and treatment options for the disease. It is these types of projects that stimulate innovative studies from other researchers. The DRC provides critical funding to support early career scientists in pursuing novel, peer-reviewed research.

 

Learn More +

Researchers Improve Cell Conversion to Support Diabetes Treatment

One of the methods of treating type 1 diabetes that researchers have been exploring is using patients’ own cells. They found that by converting stem cells into insulin-producing beta cells and then transplanting them into patients, it could stimulate the body to generate its own insulin. However, one of the challenges they faced is that beta cells only made up around 30 percent of the cells in the mixture following conversion.

Researchers in Douglas Melton’s lab at the Harvard Stem Cell Institute may have found a way to increase this percentage. A recent study found that by using single-cell sequencing, they were able to identify what the other 80 percent of cells in the mixture were. Then, by applying various molecular biology approaches, they could sort the cells based on expression patterns. Since beta cells contain a specific protein that other cells do not, they had another way to filter these cells out of the mix and increase the overall concentration that would be implanted into patients with type 1 diabetes.

Scientists at Semma Therapeutics also found a way to collect insulin-producing beta cells by separating all of the cells and then allowing them to cluster back together through their natural attraction to the same type of cell. This also increased the concentration of beta cells, and they could create a mixture that was around 80 percent beta cells versus the previous 30 percent.

The researchers are currently conducting more tests to determine what balance of beta cells versus other cells is most effective for regulating beta cell function and stimulating the production of insulin. However, now they have a greater understanding of the cell makeup during the conversion process and how to separate specific cell types.

This is another step toward improving treatment options for type 1 diabetes and potentially finding a cure. Advanced research is necessary for creating change. The Diabetes Research Connection provides funding for novel, peer-reviewed research studies focused on the prevention, treatment, and cure of type 1 diabetes, as well as improving quality of life for individuals living with the disease. Early career scientists can receive up to $50K to support their research.

Learn More +

Enteroviruses May Be Linked to Higher Type 1 Diabetes Risk

As with many diseases, type 1 diabetes is triggered by both genetic and environmental factors. There is not a single cause that can be pinpointed when it comes to why insulin-producing beta cells are destroyed by the body. However, researchers are constantly discovering different factors that may contribute to this process. A recent study found that children diagnosed with type 1 diabetes (T1D) may have higher levels of enterovirus A (EV-A) in their gut than children without T1D.

In comparing faeces and plasma viromes and data for a birth cohort of 93 Australian children, results showed that 62 percent of children tested positive for at least one vertebrate-infecting virus. The researchers tested samples for all known vertebrate-infecting viruses, and five EV-A types came back as significantly abundant in children at the onset of T1D diagnosis than in control cases.

Viruses often survive longer in the gut than in the blood, so the prolonged presence of enteroviruses in the gut may increase the risk of these infections spreading to the pancreas. In turn, this may contribute to the body’s immune system attacking and destroying insulin-producing beta cells and triggering T1D.

The study opens doors for additional research regarding EV-A and viral load in general as it relates to T1D. These findings could potentially lead to the development of targeted vaccines for these identified viruses to help protect against the development of type 1 diabetes. It is yet another step toward understanding this complex disease and working toward a cure.

The Diabetes Research Connection (DRC), though not involved in this study, stays abreast of the latest research and discoveries in the field to support future advancements. The DRC provides critical funding to early career scientists to support novel, peer-reviewed studies related to the diagnosis, treatment, and prevention of type 1 diabetes.

Learn More +

HbA1c Levels May Influence Preterm Birth Risk

Maintaining healthy HbA1c levels is essential for individuals with type 1 diabetes (T1D), but it may be especially critical for women seeking to have children. A recent study out of the Karolinska Institutet in Stockholm found that higher HbA1c levels during the periconceptional period may increase risk of preterm birth.

The study compared incidences of preterm birth for 2,474 babies born to women with type 1 diabetes, and 1,165,216 babies born to women without diabetes. They were all single births; no multiples. The researchers found that, overall, preterm birth occurred in 22.3 percent of babies born to women with T1D verses 4.7 percent of babies to women without diabetes. Broken down even further, the results revealed that the higher the woman’s periconceptual HbA1c level, the higher the risk for preterm birth. When the HbA1c level was below 6.5 percent, there was a 13.2 percent incidence of preterm birth compared to a 37.5 percent incidence when the HbA1c level was at or above 9.1 percent.

However, it is important to note that researchers found, “Preterm birth among women with T1D was strongly linked to periconceptual HbA1c levels, although women whose HbA1c levels were consistent with recommended target values were also at increased risk for preterm birth as well as other adverse pregnancy outcomes.”

This study helps to raise awareness about the risk of preterm birth for women with T1D and the importance of monitoring and managing blood sugar levels. T1D can impact many aspects of an individual’s life, and that includes pregnancy. Gaining a better understanding of these effects can support improved treatment and overall healthcare.

The Diabetes Research Connection (DRC) stays abreast of the latest industry findings and provides critical funding for early career scientists pursuing T1D-related research. Donations from individuals, corporations, and foundations make it possible for these projects to move forward and for innovative research to continue.

Learn More +

Gestational Diabetes May Increase Risk of Type 1 Diabetes in Children

Over the years, researchers have identified a variety of potential risk factors and triggers for the development of type 1 diabetes. While they know that diabetes risk runs in families – having a parent with T1D puts children at increased risk – a recent study found that gestational diabetes may also be a risk factor. Women who develop gestational diabetes do not usually have a history of the disease, and it often resolves once they have given birth.

However, the development of this condition may put their offspring at greater risk for T1D.  The study found that when mothers had gestational diabetes, children were twice as likely to develop diabetes by age 22 than those children born to mothers without gestational diabetes. A limitation of the study was that it was unknown whether children were diagnosed with type 1 or type 2 diabetes, though type 1 is more common in children.

The study involved 73,180 groups of mothers, fathers, and offspring who live in Quebec, Canada. If there was a previous history of diabetes, heart failure, or cardiovascular disease in either parent, the group was excluded from the study. Factors such as the mother’s gestational age and other maternal demographics were also adjusted for when analyzing risk and results.

Understanding the potential risk may help parents to be more alert to potential signs of diabetes in their children such as abnormal thirst, frequent urination, unusual weight loss, or fatigue if the mother experienced gestational diabetes. This can allow children to be tested and diagnosed sooner so that they can better manage their health.

Additional research is needed to address limitations of this study and also to further explore the severity of the disease in children born to a mother with gestational diabetes versus those who were not. Researchers are unclear at this point whether there is any significant difference.

It is these types of studies that stimulate new research and questions in regard to type 1 diabetes. The Diabetes Research Connection (DRC) strives to provide critical funding for early career scientists so that they can carry out research related to the diagnosis, treatment, and prevention of T1D, as well as improving quality of life for those living with the disease. To learn more about current projects and support these endeavors, visit http://diabetesresearchconnection.org.

 

Learn More +

Researchers Identify Key Protein Fragment that May Trigger Type 1 Diabetes

While the basics of type 1 diabetes (T1D) have been understood for years—the body’s immune system mistakenly destroys insulin-producing beta cells—the reasoning behind it has remained a mystery. Researchers have yet to identify exactly why this process occurs and what causes it. They may be a step closer as a recent study shows that an altered protein fragment may be the culprit.

The human body is filled with T cells that are constantly on the lookout for foreign bodies and infected cells. When their receptors sense these problems, they activate the immune system to destroy the affected cells. Normally, any T cells with receptors for proteins that occur naturally within the body are destroyed before they make it out of the thymus. This prevents them from attacking proteins that should be in the body, which in this case are insulin proteins. But scientists believe that some may escape before this process occurs, and therefore they mistakenly trigger an attack against insulin-producing cells which in turn leads to type 1 diabetes.

Researchers took a closer look at the structures that bind T cells to insulin fragments and found a specific fragment that may activate T cells to destroy insulin-producing cells. It is known as the B:14-22 fragment. They created a molecule where all of the pathogenic T cells and protein fragments fit very tightly together, but in order to improve their connection, they altered the insulin fragments. In doing so, they found that this activated the pathogenic T cells which led to an autoimmune attack on the cells.

They found that the body naturally creates altered fragments through a process called transpeptidation. When proteins are broken apart in the cell, they are recycled and may fuse together with other protein fragments. This generates a new configuration of proteins. Researchers believe that some of these new fragments could have just the right structure to activate T cells leading to the development of type 1 diabetes.

These findings may help scientists to create more effective methods for preventing and treating type 1 diabetes. Having a better understanding of what is happening on a cellular and molecular level allows for more targeted focus on coming up with a cure.

The Diabetes Research Connection (DRC) is excited to see where this study may lead and what it could mean for future diabetes treatment. It may also stimulate new studies from other researchers building on these findings. The DRC provides critical funding to early career scientists in order to support novel research on type 1 diabetes. Empowering more research could open new doors.

 

Learn More +

Exploring the Impact of Type 1 Diabetes on Standardized Testing

Though type 1 diabetes (T1D) can be diagnosed at any age, it is typically diagnosed in childhood. That means that thousands of children grow up and go through school while managing this disease. A recent study looked at the potential effects of T1D on standardized test scores of Danish children.

Researchers evaluated data on standardized reading and math tests from 631,620 Danish public school children in grades 2, 3, 4, 6, and 8. Of the more than 630,000 participants, 2,031 had T1D. After analyzing more than one million reading test scores and nearly 525,000 math test scores, they found that there was no significant difference in results between those children with diabetes versus those without. Adjustments were made for grade, test topics, and year, and comparisons were made both with and without adjusting for socioeconomic status. In both cases, there were no statistically significant differences in results.

It is encouraging to see that the presence of T1D has not had a major impact on standardized testing performance, at least for the Danish schoolchildren who participated in the study. T1D affects many aspects of a person’s life, and it can be difficult to effectively manage, especially for children.

The Diabetes Research Connection (DRC) stays abreast of diverse studies that look not only at how T1D develops and is treated but also its impact on quality of life. DRC provides funding that enables early-career scientists to pursue novel research studies on all facets of the disease in an effort to advance understanding and improve outcomes.

 

Learn More +

Could Enteroviruses Play a Role in Type 1 Diabetes?

There is no single cause of type 1 diabetes (T1D). Though scientists know that T1D involves the body destroying insulin-producing islet cells in the pancreas, there is not one specific trigger. In fact, researchers believe that genetics, environment, and immunologic capability all play a role and put individuals at different risks for developing the disease.

A recent study from investigators at Columbia University’s Mailman School of Public Health has found that the presence of certain non-polio enteroviruses may impact islet autoimmunity and lead to type 1 diabetes. They looked at the abundance of these viruses in blood and stool samples from 93 Australian children. Forty-three of the children had type 1 diabetes precursor islet autoimmunity while 48 children were matched as controls.

Using an incredibly powerful viral sequencing tool, they found 129 viruses—including five enteroviruses—that were present in higher levels in children with islet autoimmunity than those in the control group. Individuals with strong immune systems tend to eliminate enteroviruses rather quickly, usually within three to four weeks. With a slower immune response, it could take up to three months.

Risk increases when these viruses spread to children’s pancreases. Scientists are exploring how they affect pancreatic islet cells and interfere with function potentially causing beta-cell destruction and type 1 diabetes. While more research is necessary to further understand the impact enteroviruses may have, these new findings help scientists to refine their studies of the disease and its development.

While not involved with this study, the Diabetes Research Connection supports novel, peer-reviewed research studies focused on the development and treatment of type 1 diabetes as well as improving quality of life for individuals living with the disease. Up to $75,000 in funding is available for early career scientists through support from individuals, corporations, and foundations.

 

Learn More +

Oral Drug Could Help Manage A1C in Patients with Type 1 Diabetes

A major challenge for individuals living with type 1 diabetes (T1D) is reaching target A1C levels. Despite careful management of the disease and regularly checking blood sugar, many people’s A1C is still higher than recommended. While individuals with type 2 diabetes have a variety of medications they can take to help manage blood sugar, those with T1D must rely on insulin.

However, that may be changing. While insulin would still be necessary, a new oral drug may help individuals with T1D to achieve target A1C levels. The drug – sotagliflozin—prevents the kidneys from reabsorbing sugar and delays the absorption of glucose in the gastrointestinal tract. This means that there is less sugar in the blood because more of it is lost through urine output. According to researchers, there was a “two-fold increase in the number of patients who reached the target A1C level while on the drug.”

In addition to achieving improved A1C levels, many participants also experienced weight loss and a decrease in the amount of insulin needed to manage their T1D. This is a major breakthrough for patients with T1D as it would be the first ever oral antidiabetic drug for the disease in the United States. Three clinical trials encompassing 3,000 participants have been conducted so far to test safety and efficacy, and the drug is slated for a vote by the FDA for approval.

The Diabetes Research Connection (DRC) is excited to continue following this study and the potential approval of sotagliflozin as another option in the treatment of type 1 diabetes. It would give patients another resource for helping to manage this disease and its impact on their health. The DRC is committed to supporting research that improves the diagnosis, treatment, and prevention of type 1 diabetes and enhances quality of life for those living with the disease. Learn more about current projects and how to contribute to critical funding by visiting http://diabetesresearchconnection.org.

 

Learn More +
Gladitood

Conversion of Alpha Cells to Beta Cells in Pancreas May Help Treat Type 1 Diabetes

In individuals with type 1 diabetes (T1D), the immune system erroneously destroys insulin-producing beta cells. In turn, this leads to an inability of the body to control blood sugar. As a result, individuals must monitor and adjust their blood sugar on their own using a combination of finger sticks, continuous glucose monitors (CGM), insulin pumps, or insulin injections.

However, in a recent study, researchers explored the potential of reprogramming alpha cells in the pancreas to either become or function as beta cells. They used an adeno-associated virus to administer two different transcription factors – Pdx1 and MafA – into the pancreases of diabetic mice. With the overexpression of these factors, alpha cells developed into beta-like cells.

Alpha cells are ideal for reprogramming for numerous reasons including the fact that they naturally occur in abundance in the pancreas, they already function alongside beta cells in islets, and there are no apparent negative effects on glucose metabolism from reducing alpha cell levels, among other reasons.

Upon administering the transcription factors, euglycemia was restored within two weeks and maintained for four months. In addition, glucose response improved as well. After four months, autoimmune diabetes returned. However, this sheds light on potential therapeutic approaches for treating and managing diabetes and could be used in conjunction with immunosuppression for improved insulin production and blood glucose management.

Further testing is needed to determine if this approach is as effective in human pancreatic cells as it is in mouse models, though there have been some studies involving human islets in which alpha-to-beta-cell conversion occurred.

It is these types of studies that increase understanding of T1D and potential therapeutic treatment options. The Diabetes Research Connection (DRC), though not involved in this study, strives to support early career scientists in pursuing novel research studies aligned with preventing and curing T1D as well as improving quality of life for those living with the disease. DRC raises critical funds to enable these projects to move forward.

 

Learn More +

Pumps and CGMs Help to Manage A1C Levels for Individuals with Type 1 Diabetes

A1C tests show an average blood sugar level over the past two to three months. This is important not only for helping to diagnose type 1 and type 2 diabetes but also for managing the disease. Healthy individuals without diabetes should have an A1C level below 5.7%. For those with diabetes, a level of 7% or less while using insulin is the target and considered being well controlled. If A1C levels are higher, it may mean that changes are needed to the person’s treatment regimen.

A recent study of participants in the T1D Exchange Clinic Network found that even with high quality care, many people are still not meeting A1C goals. Out of more than 20,000 participants, only 21% of adults had an A1C below 7%, and only 17% of youth had an A1C below 7.5%. These statistics are likely to be even lower for the general U.S. population with T1D who do not participate in the T1D Exchange Clinic Network.

On a positive note, the study found that those who use continuous glucose monitors (CGMs) and insulin pumps tended to have better outcomes. Since the 2010-2012 study, use of CGMs increased by 30%, and use of insulin pumps increased by 6%. Compared to non-CGM users, those who used the device had A1C levels that were about 1% lower.

Furthermore, these devices also had an impact on hypoglycemic episodes and diabetic ketoacidosis (DKA). Only about 5% of CGM and pump users experienced severe lows compared to 7% of non-CGM users and 9% of non-pump users. CGM and pump users also had fewer incidences of DKA.

While there is still more work to be done to better control diabetes and A1C levels, the use of CGMs and insulin pumps seem to be beneficial for many individuals using them. With increased awareness and education about these options, as well as improved access, there is the potential to benefit even more individuals with T1D and help manage A1C.

The Diabetes Research Connection is always looking for new and innovative research projects to fund that support advancement in understanding T1D as well as preventing and curing this disease and improving quality of life for those living with it. Early career scientists can receive a grant ranging from $25,000 to $75,000 for their research project.

 

Learn More +
t1d research

Senescent Cells May Play Integral Role in Type 1 Diabetes

For years, the general consensus among scientists was that type 1 diabetes (T1D) was caused by the immune system erroneously destroying insulin-producing beta cells. Researchers have yet to determine exactly why the immune system reacts this way in some people but not others. A new study exploring cellular changes prior to the development of diabetes may have unlocked an important piece of the puzzle.

Research conducted by a team from the UCSF Diabetes Center has revealed that secretory senescence in some insulin-producing beta cells in the pancreas may be a trigger for this massive cellular destruction. When DNA damage causes cells to malfunction and harm surrounding cells, that is when the immune system kicks in and attacks the beta cells. But researchers have found this only occurs once the senescence has become widespread. If these senescent cells are eliminated early on, it may help prevent the onset of T1D because only damaged cells would be destroyed while healthy cells would remain.

The scientists studied both mouse models and pancreatic tissue from deceased human donors with diabetes. By administering an FDA-approved second-line chemotherapy agent called ABT-199 or Venetoclax, they were able to selectively target and destroy senescent beta cells in the pancreas. In their study, only 30 percent of mice given this drug developed T1D, while 75 percent of control mice developed T1D. Furthermore, the drug did not have any direct impact on healthy beta cells or the immune system in general.

Overall, they found that the risk of developing T1D could be decreased through the use of ABT-199. Further studies are necessary to determine whether periodic administration of the drug continues to clear senescent cells and keep the disease at bay. If so, this could become a potential new treatment option in the fight against T1D.

The Diabetes Research Connection (DRC) is interested in seeing how this discovery plays out and impacts future diabetes research and treatment. It could open doors to new treatment therapies and approaches for decreasing the risk of T1D through early intervention. The DRC supports early career scientists in accessing critical funds to support novel research studies focused on the prevention, treatment, and cure of T1D as well as improvements in quality of life for individuals living with the disease. To learn more, visit http://diabetesresearchconnection.org.

 

Learn More +

Removing Senescent Beta Cells May Help Prevent Type 1 Diabetes

Through data gathered in a DRC-sponsored research project, Peter Thompson, Ph.D., was able to secure additional funding that generated the results in this paper. Researchers explored the effects of senescent beta cells – or aging cells that no longer divide – on the development of type 1 diabetes (T1D).

In individuals with T1D, the body’s immune system attacks and destroys insulin-producing beta cells that are necessary for regulating blood glucose levels. However, researchers have found that senescent beta cells increase B-cell lymphoma 2 (Bcl-2) proteins, which in turn regulate cell death or apoptosis. By using a Bcl-2 inhibitor, researchers were able to eliminate senescent beta cells from the body which helps to stop the immune system’s destruction of insulin-producing beta cells and prevents the development of T1D.

This could be a major step forward in using the elimination of senescent beta cells as a therapeutic approach to treating or preventing T1D. More research is necessary to further explore the potential of this approach, but this study sheds new light on how the process impacts T1D and provides a greater understanding of the pathogenesis of the disease.

The Diabetes Research Connection (DRC) is proud to have played a role in providing the initial funding to enable Dr. Thompson and his team to collect necessary data to move forward and receive additional funding for the study. The DRC empowers early career scientists to pursue novel research studies on T1D through the support of individual, corporate, and foundation donations.

 

Learn More +

Could Reprogrammed α-Cells Reverse Type 1 Diabetes?

For years, researchers have been exploring different ways to promote insulin production in individuals with type 1 diabetes (T1D). They have tried to protect insulin-producing beta cells, implant new cells, leverage remaining cells, and more, all with varying levels of success. Another approach is to use existing cells within the body, be it stem cells or islet non-β-cells.

A recent study examines α-cells and pancreatic polypeptide (PPY)-producing γ-cells and their potential to become insulin-producing cells. Researchers collected these cells from both diabetic and non-diabetic human donors who were deceased and inserted them into diabetic mice. Then, they used the transcription factors PDX1 and MAFA to reprogram the cells to produce insulin. They found that the cells had a great deal of plasticity and retained their expression of α-cells markers while reversing diabetes and continuing to generate insulin after six months. This method has not yet been tested in humans.

Though more research is needed, their findings show the potential for reprogramming α-cells to do the work of insulin-producing β-cells which the body’s immune system has destroyed. The conversion of α-cells may also hold potential for treating degenerative diseases.

The Diabetes Research Connection (DRC) follows the latest research in the field and supports early career scientists in pursuing novel, peer-reviewed studies to keep the understanding of T1D going. Researchers receive 100% of funds raised by the DRC to execute studies regarding the diagnosis, treatment, and prevention of type 1 diabetes, as well as improving quality of life for individuals living with the disease. Find out more about current projects and how to support these efforts by visiting http://diabetesresearchconnection.org.

 

Learn More +

Influencing Cell Development to Support Type 1 Diabetes Treatment

One of the strategies researchers have been exploring for treating Type 1 Diabetes (T1D) is getting the body to generate new insulin-producing islet cells, or keeping it from destroying implanted cells. In individuals with T1D, the body does not produce enough insulin on its own to manage blood sugar levels because the immune system attacks and destroys these islet cells.

In a recent study, scientists at the University of Copenhagen (Denmark) and the Helmholtz Zentrum München (Germany) may have found a way to influence cell development in order for the body to produce more insulin-producing cells on its own. This could play an integral role in the development of improved treatment options for T1D.

The scientists closely examined a type of immature cells in the pancreas known as progenitor cells. They are similar to stem cells in that they can develop into different types of mature cells, but the variety is more limited, and they cannot divide and reproduce indefinitely. Mainly they become either endocrine beta cells or duct cells. Endocrine cells include islet cells.

By carefully studying the constant movement of these progenitor cells, researchers found that their development is strongly impacted by their environment and what types of structures they interact with. When they have greater interaction with the extracellular matrix laminin, they are more likely to become islet cells. When there is greater interaction with fibronectin, this leads to increased mechanical forces within the cell, in turn increasing the likelihood of development into duct cells.

Scientists believe they can transition this understanding to the development of stem cells in order to generate more insulin-producing islet cells by taking advantage of the mechanosignaling pathway. In terms of treatment options, this could contribute to the advancement of cell replacement therapies.

It is encouraging to see how researchers are enhancing and evolving their understanding of how cellular processes are related to type 1 diabetes and how these findings can support improved treatment options. Though not involved with this study, the Diabetes Research Connection strives to further these types of efforts by providing critical funding to early career scientists pursing research on T1D.

 

Learn More +

Are Diabetes Alert Dogs an Effective Resource for Managing Diabetes?

Service dogs are nothing new. There are dogs that are trained to alert to seizures or allergies, provide mobility support, work with individuals with hearing or vision difficulties, and much more. Included in this group are diabetic alert dogs who are trained to alert to low or high blood sugars in individuals with diabetes. But how accurate are these animals when detecting changes in blood sugar?

A recent study analyzed data from 27 dogs trained by Medical Detection Dogs, a UK organization, for 4,197 episodes of hyper- or hypoglycemia. They used information and records provided by the individuals paired with each dog as well as training instructors at the organization familiar with each dog-client partnership. Their findings showed a median sensitivity to out-of-range episodes (blood glucose levels that were too low or too high) of 70%; this was further broken down to a median of 83% for hypoglycemic episodes and 67% for hyperglycemic episodes. Overall, the dogs correctly alerted an average of 81% of the time.  However, four dogs were accurate for 100% of alerts.

It is important to note that results varied greatly among the dogs, and this could be contributed to many different factors including whether the owner was an adult or child, whether the dog was previously an owner’s pet or selected specifically for training, family size and lifestyle, the nature of the individual’s diabetes and how quickly blood sugar levels change, consistency with rewards and training, and the owner’s attitude toward the dog and confidence in its capabilities.

While owners should not rely solely on diabetic alert dogs to manage blood sugar, these animals can play an important role in improving quality of life. Some dogs are able to alert to decreasing or increasing blood sugar before they reach levels that are considered out of range. In addition, they can be beneficial for those who have decreased awareness of hypoglycemic episodes so that they know to check their glucose levels.

With so many factors that can influence a dog’s performance and abilities, each case is different. Using a diabetic alert dog in conjunction with a CGM or other system can provide more comprehensive support. There are few studies that have been done on the effectiveness and accuracy of medical alert dogs for diabetes, so more research is necessary to obtain a better understanding.

Organizations like the Diabetes Research Connection (DRC) support early career scientists in moving forward with novel research studies for type 1 diabetes by providing critical funding. Without these resources, some scientists may not be able to execute their work. Learn more about current projects and how to help by visiting http://diabetesresearchconnection.org.

Learn More +

Evaluating the Prevalence of Type 1 Diabetes Diagnoses in Older Adults

Many people still refer to type 1 diabetes as juvenile diabetes because approximately 85% of individuals with T1D are diagnosed in childhood. When diagnosis occurs in adulthood, it is often type 2 diabetes. However, T1D can occur at any age, and more adults are being diagnosed after age 30. Though it still only accounts for approximately 4% of T1D cases, a correct diagnosis is imperative for proper treatment of the disease.

Because a higher proportion of adults develop T2D, some who actually have T1D may be misdiagnosed. A recent study compared data for 379,511 white European individuals registered with UK Biobank.  Of those individuals 13,250 developed diabetes by age 60. When divided between those with high versus low genetic risk of T1D, there were 1,286 more people diagnosed with T1D in the high-risk group than in the low-risk group.

Compared to individuals with T2D, those with type 1 tended to have lower BMIs, relied on insulin use within the first year after diagnosis, and were at higher risk for developing diabetic ketoacidosis. Some type 2 individuals were actually found to have type 1 diabetes instead when it was realized that their diabetes was not well managed using strategies other than insulin, and that they required increasingly higher doses.

There have been very few studies conducted on the prevalence of T1D diagnosis in older adults because so many individuals are diagnosed at a young age. Testing for autoantibodies and C-peptide can be very beneficial, but it is not always accurate in confirming a diagnosis because some people have false positives. However, it can be used to help differentiate between T1D and T2D and more accurately diagnose adults.

“I recently diagnosed someone with new-onset T1D at 82 years old. We are definitely seeing more of this. Especially when we test for the antibodies as soon as possible,” says one of the Diabetes Research Connection’s esteemed Scientific Review Committee members, Dr. Athena Philis-Tsimikas.

The combination of genetic susceptibility and antibody testing has helped to raise awareness of the number of adults being newly diagnosed with T1D, though more research is still needed. It is essential that individuals be correctly diagnosed as soon as possible in order to receive the most effective treatment for managing their diabetes.

The Diabetes Research Connection (DRC) strives to provide valuable funding for early career scientists who are researching type 1 diabetes so that they can advance understanding, diagnosis, and treatment of the disease and one day find a cure. Learn more about current research projects and how to help by visiting http://diabetesresearchconnection.org.

Learn More +

Diabulimia: Battling Type 1 Diabetes and Eating Disorders Together

In managing type 1 diabetes (T1D), individuals can become very focused on the numbers associated with their condition – blood sugar levels, A1C, weight, insulin dosage – as well as what they eat. The food they consume impacts blood sugar and insulin needs. Some people struggle with not just T1D, but an eating disorder as well.

Dealing with diabetes can cause changes in weight. Some people lose weight quickly before diagnosis and gain it back once they begin treatment to help their body. This can be difficult to deal with, and individuals may begin restricting their insulin in order to control their weight, a condition known as diabulimia.

This can be very dangerous as their blood sugar levels can spiral out of control and increase risk of diabetic ketoacidosis, bacterial infections, muscle atrophy, dehydration, delayed wound healing, peripheral neuropathy, kidney disease, and more. These issues can become potentially fatal if not properly treated.

Researchers recently evaluated 11 online blogs of individuals with diabulimia to explore their experiences with this condition and the challenges they have faced. The bloggers expressed a variety of motives for choosing to restrict their insulin, as well as diverse complications from doing so. However, they found that having a strong support system, recognizing triggers for relapse, and improving diabetes self-management were beneficial to recovery.

Treating diabulimia can be difficult because rapidly altering blood glucose levels can be dangerous. It must be done carefully under medical supervision. In addition, treatment cannot only address diabetes management. It must also focus on eating disorders and improving the person’s relationship with insulin, food, and self-perception. There are many underlying issues that should be taken into consideration. Treatment providers should be well-versed in both T1D and eating disorders.

More in-depth research is necessary to gain a better understanding of effective interventions and treatment approaches for diabulimia. Organizations like the Diabetes Research Connection (DRC) provide critical funding for peer-reviewed, novel studies regarding T1D. Early career researchers can make strides in advancing diabetes management and eventually finding a cure. To learn more about current projects or support these efforts, visit http://diabetesresearchconnection.org.

Learn More +

Exploring Collagen as a Minimally Invasive Approach to Managing Type 1 Diabetes

Diabetes management is a full-time job. Individuals with type 1 diabetes (T1D) don’t get a day off; they must be constantly monitoring their blood sugar and administering insulin as necessary. There are many devices that can assist with this process, but it is still a constant concern. However, researchers from Purdue University and the Indiana University School of Medicine may have developed a new approach that could manage glucose levels for up to 90 days at a time.

By combining pancreatic cells with collagen – a natural protein in the body already – they may be able to decrease rejection and enhance insulin independence. Previous methods have focused on injecting islet cells directly into the pancreas because it has a strong blood flow to transport insulin and glucose.  This tends to be a rather invasive procedure, though, and the body still destroys a significant portion of the transplanted islet cells.

This new treatment is administered under the skin just like other injections. The collagen solution solidifies and the body recognizes the collagen, so it does not destroy it. Instead, it provides blood flow that helps transport the insulin released by the islet cells contained within the solution. The procedure is minimally invasive and could be done in an office setting rather than an operating room.

Initial studies were conducted on mice, and now the researchers are ready to test this approach on naturally diabetic dogs and eventually humans.  Diabetes occurs in dogs very similarly to how it does in humans. The researchers will work with the College of Veterinary Medicine at Purdue for these clinical trials.

In mice with diabetes, pre-clinical trials found that diabetes was reversed for at least 90 days when a twin mouse donor was used to collect islet cells, and at least 40 days when a non-twin mouse donor was used for islet cells.  In addition, virtually all of the cells survived the transplant regardless of donor type. This could potentially eliminate the need for multiple donors which are required for current treatments due to the destruction of transplanted cells by the immune system. Giving individuals with T1D a shot every 40 to 90 days to maintain blood sugar could provide a great deal more freedom than they currently have.

It is these types of studies that have the potential to change the lives of individuals living with T1D for the better. Researchers have made significant advancements over the years in better understanding the disease and developing treatment strategies that could lead to an eventual cure. Diabetes Research Connection (DRC), though not involved in this study, is interested to see how the clinical trials progress and what it could mean for the future of diabetes management.

DRC is committed to supporting early career scientists pursuing novel research studies on type 1 diabetes to prevent and cure the disease as well as improve quality of life and minimize complications. Mainstream funding is highly competitive, and the DRC gives young researchers another option for receiving the support they need to drive projects forward. To learn more about current projects and support these efforts, visit http://diabetesresearchconnection.org.

Learn More +

Australian Government Increases Support for Individuals with Type 1 Diabetes

Managing diabetes is expensive. It requires buying insulin, testing supplies, monitoring devices and supplies, emergency supplies, and more. There is also the cost of doctor visits, specialist visits, and emergency care in the event of severe hyperglycemia, hypoglycemia, or other issues. In some cases, poor diabetes management and overall health are a result of not being able to afford consistent care.

The federal government in Australia is taking steps to change this. The government has committed an additional $100 million over four years to increase access to free continuous glucose monitoring (CGM) devices for individuals with type 1 diabetes (T1D). This has the potential to save families thousands of dollars in out-of-pocket expenses each year. While there are some eligibility requirements, in general the expansion of services will include children and adolescents with T1D or conditions requiring insulin, pregnant women with T1D, and adults with T1D who have a high clinical need.

Patients can choose from a CGM sensor that is attached to the stomach or the arm. Arm sensors are used with the FreeStyle Libre Flash Glucose Monitoring System, and information is sent directly to the patient’s cell phone or diabetes management device. This allows closer tracking of glucose levels without constant finger sticks, and information can be easily shared with healthcare providers. In addition, having access to CGM devices may reduce patient anxiety and stress regarding diabetes management, as well as decrease emergency hospital visits.

It is encouraging to see the government recognizing the importance of quality diabetes care and stepping up to support patients living with T1D to make diabetes management more affordable and accessible. The Diabetes Research Connection (DRC) is interested to see the influence this could have on future diabetes care and the impact it will have on patients. The DRC is committed to raising funds for peer-reviewed, novel research studies on T1D by early career scientists. These projects play an instrumental role in advancing knowledge, treatment, and potential cures for the disease. Learn more about current research projects and support these efforts by visiting http://diabetesresearchconnection.org.

Learn More +

Multiple Daily Injections May Improve Glycemic Control During Pregnancy for Women with T1D

Effectively managing blood sugar can be difficult in normal situations, but it can be even more challenging during pregnancy. Women must be cognizant of not only their own health, but also that of their unborn child. Infants are at risk for neonatal hypoglycemia. A recent study examined the impact of multiple daily injections (MDI) versus using an insulin pump on glycemic control during pregnancy for women with type 1 diabetes.

The study involved 123 women using MDI therapy and 125 women with insulin pumps. The researchers based the study on the treatment the women were already using prior to the trial; they did not assign a treatment method. Participants spanned multiple countries including the United States, Canada, England, Ireland, Scotland, Spain, and Italy. Women entered the study during their first trimester, and it lasted until they were at 34 weeks of gestation.

During this time, HbA1c levels were measured. The results showed that both treatment methods were equally effective during the first trimester with no statistically significant differences. However, at 34 weeks gestation, women who used MDI therapy showed a greater decrease in HbA1c levels versus women using insulin pumps. In addition, insulin pump users reported higher levels of gestational hypertension, neonatal hypoglycemia, and neonatal intensive care unit admissions for longer than 24 hours. However, these women also reported lower levels of hypoglycemia-related anxiety than those using MDI therapy, but also had lower levels of general well-being.

Overall, it appeared that MDI therapy resulted in greater decreases in HbA1c levels and improved glycemic control. There is still more research necessary, however, to verify these results. There were several factors that may have influenced findings and outcomes.

This study shows the importance of understanding the effects of T1D on different conditions such as pregnancy and the value of researching various treatment options to help women make more informed decisions regarding their health. Though not involved in this study, the Diabetes Research Connection follows the latest trends and developments in the field and supports early career scientists by providing critical funding for novel research regarding T1D. Continued funding is essential for advancing research and diabetes care. To learn more, visit http://diabetesresearchconnection.org.

Learn More +

20 Years Later: The Impact of the Edmonton Protocol

Management and treatment of type 1 diabetes have advanced over the years, but it is interesting to see what has withstood the test of time. For instance, islet cell transplantation (ICT) was first used in humans in 1989. Though the protocol changed a bit in 2000, the concept has remained relatively the same ever since. It is known as the Edmonton Protocol.

Researchers have followed the Edmonton Protocol since 1999, tracking factors such as the number of procedures, adverse events, and insulin independence. Studies have shown that insulin independence rates have been fairly consistent from 1999 through 2015 with around 50% of patients maintaining insulin independence after one year, and 25% maintaining insulin independence after five years. In addition, fewer patients have experienced adverse events over the years, and whole-body immunosuppression has become more localized. However, the number of centers performing ICT and the number of patients receiving this treatment have also declined.

The Protocol continues to rely on the use of cadaver islet cells which are inserted into the body of a patient with T1D.  The transplanted cells are protected by immune suppression or some type of encapsulation to reduce the risk of the body attacking and destroying these cells.

One challenge that has persisted over the years is identifying a sustainable source of islet cells aside from cadavers. Researchers have been testing methods for using human stem cells or animal islet cells, but more tests are needed to potentially make these options feasible. Furthermore, the issue remains of protecting cells in the long-term. Currently, the best option is immunosuppression, but even that has limited effectiveness. While there have been advances made in the medications and encapsulation devices used, there is still work that needs to be done to address undesirable side effects such as decreased ability of the body to fight off diseases or infection.

It is interesting to see how the Edmonton Protocol has remained the standard for ICT for 20 years, and the Diabetes Research Connection (DRC) continues to follow progress and changes related to this type of treatment for T1D. T1D continues to affect around 1.25 million Americans, and researchers are always looking for improved options for treating, managing, and potentially curing this disease.

The DRC provides necessary funding to early career scientists to conduct novel research studies related to type 1 diabetes. These projects are aimed at preventing and curing T1D as well as minimizing complications and improving quality of life for those living with this disease. To learn more about current research projects and support these efforts, visit http://diabetesresearchconnection.org.

Learn More +

Diabetic Ketoacidosis Risk May Increase with Cannabis Use

Legalization of recreational and medicinal cannabis use has increased throughout the United States, but that does not mean that it does not come with risks. While cannabis can have positive effects for certain conditions, it may also be dangerous for others. A recent study found that using cannabis may double the risk of individuals with type 1 diabetes of developing diabetic ketoacidosis.

In a small, self-reported study of 450 individuals in Colorado with type 1 diabetes, approximately 30% reported using cannabis within the past 12 months. Of that group, around 40% smoked, used edibles, or vaped at least four times per week. The study found that while 8.2% of non-users had been hospitalized for diabetic ketoacidosis within the last year, this jumped to more than 20% for cannabis users. Furthermore, individuals with type 1 diabetes who used cannabis also had higher average HbA1c levels than non-users. Researchers believe the increased risk may come from the fact that “cannabinoids alter gut motility and cause hyperemesis.”

However, there is still more research necessary to further explore this risk as the study had several limitations. Many of the participants who reported using cannabis were younger with lower income and lower use of diabetes technology such as insulin pumps and continuous glucose monitoring (CGM). In addition, access to healthcare was not taken into consideration. Furthermore, some participants may have had underlying conditions that also impacted their risk of developing diabetic ketoacidosis.

Regardless, this study opens doors for more in-depth research regarding the effects of cannabis use on type 1 diabetes. It is important to understand how this drug may impact health, treatment, and quality of life.

The Diabetes Research Connection (DRC), though not involved with this study, strives to support novel research studies regarding all aspects of type 1 diabetes by providing essential funding to early career scientists. This is made possible by donations from individuals, corporations, and foundations, and 100% of research funds go directly to the scientists. To learn more about current projects and how to help, visit http://diabetesresearchconnection.org.

Learn More +

Researchers Examine Gut Bacteria in Children for Risk Factors for T1D

In an effort to better understand how type 1 diabetes may develop, researchers took a closer look at how gut health changes from infancy through childhood and into adulthood. They used data collected through The Environmental Determinants of Diabetes in Youth (TEDDY) study, which utilized reports from Finnish, German, Italian, Mexican, American, and Turkish children. This particular study on gut bacteria focused on 783 children between the ages of three months and five years from Finland, Germany, Sweden, and the United States.

Some of the factors they examined were whether children were breastfed or formula fed and for how long, any illnesses they contracted, antibiotics they took, environmental changes, and life experiences. Their gut microbial profile was determined through stool samples. One interesting finding was that when there were more Bacteroides species and a decreased production of short-chain fatty acids, there was an increased susceptibility to islet autoimmunity (IA) or type 1 diabetes (T1D).

The researchers found that the gut microbiomes differed greatly between participants, and there was a marked difference in children who were breastfed versus those that were not, as well as once solid foods were introduced into their diet. Breastfeeding showed higher levels of an enzyme that helps with milk fermentation, while solid foods increased enzymes that help metabolize fiber. In addition, participants who had taken oral antibiotics showed disrupted microbial stability along with decreases in some strains of Bifidobacterium. However, early probiotic supplementation helped protect control subjects against islet autoimmunity.

All of these factors may play a role in the development of islet autoimmunity or T1D. This study has increased awareness of the role that environmental factors may play in T1D along with genetics. There are still numerous issues this study did not address, but it is a strong starting point for further research, especially when it comes to the influence of breastfeeding and oral antibiotics on the development of T1D.

The Diabetes Research Connection (DRC) is interested to see how this study may impact future research in T1D and furthering the understanding of factors related to disease development and prevention. The DRC supports early career scientists pursuing novel research related to the prevention and treatment of T1D as well as improved quality of life for individuals living with this disease. Learn more about current studies and how to help by visiting http://diabetesresearchconnection.org.

Learn More +

Nasal Glucagon May Become New Option for Treating Hypoglycemia

When blood sugar drops and hypoglycemia occurs, it is critical for individuals with type 1 diabetes to receive immediate treatment to raise their blood sugar. If left untreated, it can lead to severe confusion, seizures, or even loss of consciousness. One of the main ways of treating hypoglycemia is administering glucagon.

Glucagon is a hormone that stimulates the body to convert glycogen into glucose. It also keeps the liver from consuming too much glucose so that it can be circulated in the bloodstream instead. Traditionally, glucagon is delivered through an intramuscular injection. A solution is mixed to dissolve the glucagon, then it is administered by syringe.

However, many caregivers – or even bystanders – may be hesitant to give someone else a shot of glucagon. Preparing the syringe and shot is a multistep process and can be confusing if the person is not properly trained. Plus, they are under considerable stress in emergency situations where it must be given, which can complicate things even further.

A new study has found that nasal glucagon may be just as effective as intramuscular glucagon in raising blood sugar levels during episodes of hypoglycemia. There is no preparation necessary before administering the medication. It is a powder that comes in a single-use device that is sprayed up the nose. It isn’t even necessary for the patient to inhale because the powder is absorbed on its own.

Both treatment methods were tested on 70 adult participants with type 1 diabetes. A state of hypoglycemia was induced, and then they were treated with either the intramuscular or nasal glucagon. One to seven days later, the process was repeated, and the other form of medication was administered. In 100 percent of cases, hypoglycemia was reversed and participants had no serious adverse events. In 97 percent of cases, treatment success was achieved within 15 minutes.

This new treatment option was presented at the European Association for the Study of Diabetes (EASD) by Leona Plum-Moerschel, MD, of Profil Mainz, Germany. According to Plum-Moerschel, “I think we can all agree that the safety profile is very much acceptable for an emergency treatment. I personally would expect that, due to its simplicity of use, nasal glucagon will create a greater community who can render quick aid in a rescue situation.”

The Diabetes Research Connection (DRC) is interested to see if this nasal formulation will be brought to market and how it will affect the treatment of hypoglycemia in children and adults. It is encouraging to see treatment options becoming more user-friendly so that even non-medical personnel can effectively administer emergency medications.

The DRC supports research geared toward the treatment and prevention of type 1 diabetes, as well as improvement of quality of life for those living with the disease. Access to funding is essential for scientists to continue advancing their research, and the DRC provides these types of resources. To learn more about current projects and donate to support these efforts, visit http://diabetesresearchconnection.org.

Learn More +

More Adults May have Type 1 Diabetes Than Previously Thought

Type 1 diabetes (T1D) used to be known as juvenile diabetes because it is often first diagnosed during childhood. Since the pancreas produces little to no insulin, difficulty regulating blood sugar is typically noticed early on. However, that is not always the case. There are also many individuals who are not diagnosed with T1D until after age 30. In addition, they may be mistakenly identified as having type 2 diabetes rather than type 1.

A recent study compared data from the UK Biobank and also conducted clinical trials to determine how adults are diagnosed and treated when diabetes is suspected. Many people were initially diagnosed with type 2 diabetes and did not receive insulin treatment. They used an oral glucose-lowering medication in order to manage their blood sugar. But even when using rapid acting insulin, some still had difficulty with blood sugar control.

Approximately 5 percent of adults diagnosed with T2D actually have T1D. While this may not seem significant, proper diagnosis is critical to providing accurate treatment and education for patients. In addition, insurance may not cover the cost of supplies for those with T2D, but insulin pumps and continuous glucose monitors may be covered for those with T1D. This can make a major difference in care for many people.

The study involved nearly 600 adults from South West England who were diagnosed with diabetes after age 30 between 2007 and 2017. Results showed that 123 participants (21 percent) had type 1 diabetes with severe insulin deficiency requiring continuous insulin treatment within three years of diagnosis. There were 306 participants diagnosed with type 2 diabetes based on a peptide level of 600 pmol/L or greater for at least three years after initial diagnosis. Another 115 participants were not included in the analysis due to indeterminate results. The study also included 220 participants who had been diagnosed with T1D at age 30 or younger for comparison purposes.

While symptoms are often similar, the study found that “rapid insulin requirement was highly predictive of late-onset type 1 diabetes, with 84 percent requiring insulin within 1 year. And of all the patients treated with insulin within 3 years, 57 percent developed sever endogenous insulin deficiency consistent with type 1 diabetes.” Compared to participants with T2D, those with T1D typically had a lower BMI, were more likely to have a positive islet autoantibody test, and had higher genetic risk scores for T1D.

It can be difficult to differentiate between the two types of diabetes, but medical providers should carefully monitor those they believe may have T1D and conduct related tests to determine whether they should be treated initially using insulin as opposed to an oral medication.

The study was presented at the European Association for the Study of Diabetes (EASD) 2018 Annual Meeting by Nicholas J. Thomas, MD, from the University of Exeter, United Kingdom. Dr. Thomas’ team is working on developing algorithms to improve the accuracy of diabetes diagnoses in order to provide the best care for patients.

Accurate diagnosis of type 1 or type 2 diabetes is essential for effective care and patient education. The Diabetes Research Connection supports research related to T1D and advancing understanding related to the diagnosis, treatment, and prevention of this disease. Early career scientists are provided with up to $70,000 in funding to conduct peer-reviewed, novel research studies. Learn more and find a project to support by visiting http://diabetesresearchconnection.org.

Learn More +

Building a Pipeline of Young Researchers

New and innovative research is essential to continuing to expand scientific knowledge and improve the future of healthcare. Yet over the years, the biomedical community has seen a troubling downward trend in funding, support, and opportunities for young researchers. A study published in the Proceedings of the National Academy of Sciences of the United States of America investigated some potential factors for why investigators are struggling early on in their careers and not receiving as much funding to stimulate independent research.

For years, attaining an R01 from the National Institutes of Health (NIH) has been a prerequisite for young biomedical researchers to become independent investigators and start their own laboratories. Yet the average age that they receive their first R01 has steadily increased from less than 38 years old in 1980 to more than 45 years old in 2013. In 1980, 5.6% of grant funding went to investigators who were younger than 36, but by 2012, this had dropped to just 1.3%. Principal investigators over age 65 are awarded more than twice as many R01s as those under age 36.

It has become increasingly challenging for young scientists to secure necessary funds to advance their careers in research. In turn, this puts future generations of biomedical researchers in jeopardy because more scientists are becoming disheartened and exploring other career paths. It also disrupts the emergence of scientific breakthroughs from bright young minds with untapped potential.

There are many reasons why young investigators may be losing out on the fight for NIH funding. For one, some are spending more time in post-doctoral programs training and it is taking longer for them to secure faculty positions. There may also be unintentional bias from review committees to select more established investigators who have a proven track record of success rather than taking a risk on unknown scientists. Funding has been reduced over the years making the competition fiercer and the awarding of grants increasingly selective. This also means that universities must shoulder a larger portion of the costs associated with supporting research endeavors.

The Diabetes Research Connection (DRC) is reversing this trend by funding early-career scientists who then leverage funding from DRC to seek additional funding from larger foundations and NIH.

 

DRC is supporting the next generation by directing its fundraising toward early-career scientists. It recognizes that mainstream funding is highly competitive, and, as the above research has shown, is less frequently awarded to young researchers. Through DRC, scientists receive up to $70,000 from donors for their research projects, which can be enough to give them a strong foundation to conduct novel research related to type 1 diabetes. To learn more about current projects and support these efforts, visit http://diabetesresearchconnection.org.

Learn More +

The Growing Cost of Type 1 Diabetes Management

For individuals with type 1 diabetes (T1D), insulin is a life-saver. Literally. Without it, their body can go into a state of diabetic ketoacidosis where blood sugar becomes so high that the body shuts down. It can be fatal if not treated immediately. Since the pancreas does not produce enough (or in some cases any) insulin on its own, people with T1D rely on insulin daily to keep their blood sugar in check. However, the cost of this life-saving hormone has continued to increase over years, and for some, it has become unaffordable, even with insurance.
A vial of insulin can cost around $250 without insurance or other financial assistance. It is not unusual for someone with T1D to use between two and four vials every month. That means they could be paying $500 to $1,000 for a medication that is critical to their survival. Even with insurance, deductibles can be thousands of dollars. This means they must pay this money up front – in addition to monthly premiums – before insurance kicks in to help offset costs. For some, this is simply not feasible. Despite having a solid job, the cost can be too much on top of other living expenses such as rent, utilities, and food.
Unfortunately, this means that some people with type 1 diabetes have resorted to rationing their insulin supply in an effort to make it last longer. They administer less insulin than their body actually needs to keep their blood sugar within a desirable range. This can quickly spiral out of control and lead to complications such as diabetic ketoacidosis. It is a dangerous decision, but if they cannot afford more insulin, they may feel it is better than going without.
Many people are fighting for improved regulations regarding pricing for insulin as well as insurance so that people do not have to choose between paying for insulin versus other bills, or deciding how to make the insulin they do have last until they can afford more. There are organizations that can help individuals with diabetes to find financial assistance to help with the cost of insulin and other diabetes supplies, and sometimes they may be able to get insulin for free depending on the situation. Not everyone is aware of these options and resources, however, so advocacy is so important.
Type 1 diabetes is a manageable condition, but people must have access to the necessary resources in order to survive. While treatment options have improved over the years, the cost is still an issue.
The Diabetes Research Connection (DRC) strives to support peer-reviewed, novel research studies regarding type 1 diabetes treatment and management. As scientists gain a greater understanding of this disease, it may help to make future care more affordable and eventually lead to a cure. To learn more about the Diabetes Research Connection and support current projects, visit http://diabetesresearchconnection.org.

Learn More +

Increasing Polyclonal IgMs May Help Prevent or Reverse T1D

A common strategy used by researchers in treating type 1 diabetes (T1D) is to destroy or deactivate immune cells that mistakenly attack insulin-producing beta cells. There have been many variations on this approach over the years, but effectiveness has been limited. Typically, these autoreactive cells reemerge. However, tackled this issue from a different angle instead of looking at how to increase certain protective cells.

Researchers, including Daniel Moore who works with the Diabetes Research Connection, found that IgMs have immunoregulatory properties that help to limit inflammatory responses and decrease autoreactive B lymphocytes. Islet-reactive B lymphocytes have been found to produce anti-islet antibodies linked to the development of stage 1 T1D. IgM may also help to stimulate the production of regulatory T cells.

When administered in non-obese diabetic (NOD) mice, purified IgM was able to prevent the development of diabetes and increase regulatory T cells. However, IgM that was taken from pre-diabetic mice was not as effective. IgM obtained from Swiss Webster donor mice (recognized as healthy, not pre-diabetic, mice) was highly effective in reversing hyperglycemia and preventing the onset of diabetes. The researchers also used human IgM from healthy donors and found similar results.

The study shows the potential effectiveness of healthy donor IgMs in promoting normal immune homeostasis, preventing diabetes occurrence, and reversing new-onset diabetes. While immunoglobulin therapy is not a new concept, it usually contains low levels of IgM, whereas this study focused on higher levels of purified IgM. More research is necessary to further explore the potential of donor polyclonal IgM for the prevention and treatment of type 1 diabetes.

Daniel Moore, a senior author on the study, is a scientist associated with the Diabetes Research Connection (DRC). The DRC is committed to funding novel, peer-reviewed research focused on preventing and curing T1D as well as improving quality of life for those with the disease. It has played a role in supporting dozens of projects. To learn more about current studies, visit http://diabetesresearchconnection.org.

Learn More +

Factors Identified for More Effective Type 1 Diabetes Care

Managing type 1 diabetes is a complex process. Every person is different and must figure out what strategies and devices work best for their care, and that involves working together with their healthcare provider. Results of a recent audit have identified some key factors that contribute to better diabetes management from a provider perspective.

Participants in the study included top clinics that care for more than 500 individuals with type 1 diabetes. Results found that at up to 40 percent of patients achieved HbA1c levels of 58mmol/mol or lower at some centers, while in other centers only 20 percent of patients hit this target. The data was analyzed in an effort to identify factors that may have contributed to these differences.

Some of the strategies that have been found effective include providing structured education and dedicated pump clinics for patients to support them in diabetes care. More than half of the centers that participated in the audit reported having nurses and staff that were specially trained in type 1 diabetes care. Several of the centers also offered support services via phone and online to patients and focused on improving access to continuous glucose monitors (CGMs).

It may also be beneficial for treatment centers to partner with other services including psychological care and community organizations to improve outcomes for patients. Taking a collaborative approach could support patients in managing health across multiple areas thereby enhancing overall type 1 diabetes care.

The Diabetes Research Connection (DRC), though not involved in this study, is committed to advancing knowledge and treatment when it comes to type 1 diabetes. The DRC provides critical funding to support early-career scientists in conducting peer-reviewed, novel research studies. To learn more and contribute to these efforts, visit http://diabetesresearchconnection.org.

Learn More +

Advancing Diabetes Management Technology

Over the years, treatment options for type 1 diabetes have greatly expanded. From the development of continuous glucose monitors to insulin pumps to artificial pancreas systems, researchers are striving to improve the lives of those living with this disease. However, there have also been challenges regarding the accuracy, usability, and lifespan of these options.

One issue that exists is effectively coordinating treatment options to work together. Depending on the device an individual uses, it may not be compatible with a product from a different company, or even from the same company. There may be multiple steps involved in reading and responding to results in order to effectively manage type 1 diabetes.

JDRF is looking toward easing these challenges by partnering with SFC Fluidics, Inc., a medical technology company, to create an interoperable insulin pump. This device would provide continuous insulin therapy through a tubeless system, but unlike other technology, it would be an open protocol system. That means that it would be able to communicate and share information seamlessly with other devices such as CGMs or third-party technology. This would be a huge step forward in potentially improving diabetes care and management. JDRF and SFC Fluidics are currently developing and testing this technology as well as reviewing liability and regulatory requirements.

The Diabetes Research Connection (DRC) is excited to see how this project unfolds and what it could mean for the future of diabetes management. It is through the tireless work of researchers, scientists, and medical professionals that treatment options have continued to improve and more is understood about this complex disease. The DRC provides funding to early career scientists pursuing novel research studies related to type 1 diabetes in an effort to prevent and cure the disease as well as improve quality of life for those living with T1D. To learn more and support current research projects, visit http://diabetesresearchconnection.org.

Learn More +

Next Stop Cure? A Quick History of Diabetes Research

From an insulin pump that’s the size of a backpack to stem cells hitching rides on what’s the size of a band-aid, diabetes research has come a long way. It is not without tireless efforts from the scientific community, keen investors, visionaries and donors, alike, who have moved the needle.

With research funding, people managing this challenging disease have received tools that help them to live better lives. Every advancement or milestone has elevated our understanding of Type 1, achieved improved management and has gotten us one step closer to an actual cure. That’s why donating to diabetes research is so important — it’s the only way we’ll eliminate this disease.

Diabetes research milestones

The timeline of advancements

1889: Pancreatic diabetes discovered

Oskar Minkowski and Joseph Von Mering met accidentally in a library in 1889. Striking up a conversation, they began to debate whether the pancreas helped digest and absorb fats. Performing a pancreatectomy on a dog that same night, they found the dog developed glycosuria, a condition associated with diabetes that causes the production of a lot of urine. Minkowski found the urine was 12% sugar. They then depancreatized another dog and found that prevented hyperglycemia.

1921: Discovery of insulin

In 1921, Frederick Banting and Charles Best closed off the pancreatic ducts of a dog then removed the pancreas. They crushed, froze, and salted it. Then they gave this substance to a diabetic dog and found the dog’s blood sugar dropped significantly.

1922: Purification of insulin

James Collip refined Banting and Best’s insulin extraction and purification method. The new substance was tested in the first human in 1922. 14-year old Leonard Thompson was in a critical condition. He was given an insulin injection in his buttocks. This had a negative effect on him and he grew sicker. Collip worked to improve the insulin’s quality and Thompson received another injection soon after. This time, it lowered his blood sugar and saved his life.

1959: Type 1 and Type 2

Solomon Berson and Rosalyn Yalow measured how much insulin was in a diabetic’s blood. This led to the discovery that some diabetics could still make insulin, which split the diabetic world into two sections—Type 1 and Type 2.

1961: Glucagon introduced

Eli Lilly and Company succeeded in creating a pure form of glucagon, a hormone that elevates blood glucose levels. The introduction of glucagon as an injectable treatment became life-saving in emergency situations of severe hypoglycemia.

1963: The first pump

Designed by Dr. Arnold the pump that looks like a backpack delivers both glucagon and insulin.

1966: First pancreas transplant

The University of Minnesota Hospital was the first to successfully transplant a pancreas into a human. The success rate of these transplants has increased since then as better surgical techniques and immune suppressant drugs improved.

1967: Laser treatment for diabetic blinding

William Beetham and Lloyd Aiello created a laser treatment that, over the next five years, radically changed diabetic retinopathy care.  

1976: A1C Test developed

Researchers at the Joslin Diabetes Center in Boston perfected the A1C test, which can provide information about a diabetic’s average blood glucose control over the previous 2-3 months.

1978: First human insulin synthesized

Genentech discovered how to synthesize human insulin from E. coli. The scientists had to synthesize genes then put them in the E. coli bacteria. This forced the E. coli to produce insulin chains. Two chains were then combined and a human insulin molecule was made. They turned each individual bacterium into a manufacturing plant for human insulin.

1986: Insulin Pen

Insulin pens were introduced, replacing disposable syringes. Now diabetics could vary their dose. The pen also gave them more privacy as it was less obvious what the pens were for.

1990: Insulin external pump

These pumps continuously monitor sugar levels and allow the wearer more freedom and control over their sugar levels.

1999: First continuous glucose monitor (CGM)

MiniMed received FDA approval for the first CGM device in the USA. The company was later bought by Medtronic. Initially, it was called a “retrospective CGM device” and was meant to look back at a 72 hours monitoring of blood sugars.

2006: First inhaled insulin is FDA approved

Exubera was the first inhaled insulin. It was put on the market in 2006 but taken off in 2007 due to low sales. Since then researches have created Affreza, an improved version that hit the market in 2014.

2014: Stem cell islets implant

Viacyte created a therapy called VC-01, which implants a collection of young stem cells in an immune-protective container under the skin. The young stem cells develop into insulin-producing cells that release insulin when the body needs it.

2016: Hybrid closed-loop system

Medtronic receives FDA approval for the first hyped closed-loop system which connects CGM and insulin pump. It learns what an individual’s insulin needs are and takes action to minimize both high and low glucose levels. It delivers variable insulin 24 hours a day.

 

 

Learn More +

WHY SUPPORT DIABETES RESEARCH

Less than one hundred years ago, Type 1 diabetes was a mysterious, daunting disease. Parents watched their children’s health quickly deteriorate as they awaited their inevitable early demise. By the early 20th century, medical advancements, stemming from intensive research, completely transformed the fate of people living with Type 1 diabetes.

In 1889, upon removing and then replacing the pancreas of a dog, scientists found that that the pancreas played a major role in preventing high blood glucose, paving the way for future diabetes treatment advancements. One of these major advancements came over thirty years later in 1921-22, radically changing the lives of thousands: the discovery and purification of animal insulin. While this insulin greatly increased the lifespan of those with Type 1, it caused painful allergic reactions in some because of its foreign origin from pigs and cows. However, by 1978, researchers discovered how to create synthetic human insulin from E. coli bacteria, allowing increased insulin absorption without the allergic side effects.

Before the introduction of the disposable syringe in 1956, and then insulin pens in the 1980s, needles for insulin injections were commonly sharpened at home with a grinding stone. Since 1990, insulin pens can even be replaced by an external insulin pump, allowing people with T1D more freedom and control.

The first successful pancreas transplant occurred in the University of Minnesota Hospital in 1966. Pancreas transplants have provided a life-saving option for those with Type 1 diabetes with extremely poor health, and they have continued progressing in refinement, with better surgical techniques and the development of improved immunosuppressant drugs.

Unfortunately, despite the advancements, the long-term complications of Type 1 diabetes are numerous. Research, however, has been effectively diminishing their severity. In 1966, a laser treatment was developed that changed retinopathy care, a common cause of blindness with those who have diabetes. The A1C test, developed in 1976, assesses overall control of blood glucose over a span of three months, thereby showing the effectiveness of a treatment plan.

A modern-day person with diabetes can utilize resources and that wouldn’t have been possible without scientific research. Medical treatments have gone from starvation diets to compact, portable devices that control, measure and track blood glucose levels every second of the day.

Diabetes research is relatively young yet is advancing exponentially. The life of a person diagnosed with diabetes in the last decade and someone diagnosed fifty years ago is incomparable. A cure would mean liberation for people with Type 1 diabetes from constant injections, constant monitoring, and constant worry. However, it is completely unattainable without outside support. Diabetes is one of the most prevalent diseases in the United States with a multitude of costly and life-threatening complications.  Unfortunately, research for this disease still remains one of the least funded by the national government.

In order to be successful, in order to change and save lives, diabetes research requires funding. When someone supports an organization that funds research, they become a part of positive change. Support of scientific research has already transformed the world we live in: we have already cured many of the devastating diseases of the 20th century such as polio and smallpox. Be a part of the profound scientific evolution that is occurring in the 21st century. Supporting diabetes research isn’t just funding scientists and laboratories — it’s providing hope for the millions of children and adults affected by this chronic illness.

Disease prevalence versus funding

Diabetes only receives 3% of the total funding from the NIH (National Institute of Health), compared to cancer (16%) and HIV/AIDS (9%). However, there are 29 million people living with diabetes in the US, compared to 1.2 million living with HIV/AIDS and 13.4 million living with either a current or past experience with cancer. With these statistics, The NIH spends around $38 each year per person with diabetes, $417 per person with HIV/AIDS, and $2,583 per person with cancer.

Short-term complications

In addition to long-term major complications, immediate dangers may occur if a person with Type 1 diabetes has low or high blood glucose levels. These include the following:

  • Severe Hypoglycemia: extremely low blood sugars can cause seizures, loss of consciousness or death. Death from unrecognized low blood sugar upon going to sleep accounts for 6% of all deaths in people with Type 1 diabetes under forty-years old.
  • Ketoacidosis: If someone with T1D does not receive insulin, the body will break down fat to produce energy, releasing ketones into the bloodstream. When ketone levels become too high, diabetic ketoacidosis (DKA) can cause vomiting and dehydration, and even cause one to fall into a coma.

Long-term complications of Type 1

People with Type 1 diabetes may have access to insulin and blood glucose monitors, but such treatment still cannot completely prevent future complications. Common complications include:

  • Eye disease: diabetic retinopathy is the leading cause of blindness in diabetics. High blood sugar damages the blood vessels in the back of the eye, eventually causing vision loss.
  • Kidney disease: High blood sugar levels overwork the kidneys filtration system. A damaged filter allows waste products to build up in the blood, and the kidneys begin to fail (end-stage renal disease).
  • Nerve damage: Symptoms of diabetic neuropathy can range from pain to complete numbness in the legs or feet, causing severe disabling.
  • Heart disease: people with Type 1 diabetes have four times the risk of suffering a heart attack.

Everyday management of Type 1

To avoid long-term and short-term health risks, Type 1 diabetes must be managed diligently. People with T1D may have a specialized treatment plan, however, there are certain consistencies for all people with Type 1. Insulin must be taken after every meal and blood glucose levels must be checked several times a day. Special attention must be paid to the foods that a person with Type 1 diabetes consumes so that their insulin dosage is appropriately calibrated. As early as infancy, such intensive daily procedures become the responsibilities of every person managing Type 1. Better care means a better quality of life with Type 1. Diabetes research is the key to improving methods of care and ultimately finding a cure.

DRC provides funding to early-career scientists pursuing novel research studies related to type 1 diabetes in an effort to prevent and cure the disease as well as improve quality of life for those living with T1D. To learn more and support current research projects, visit http://diabetesresearchconnection.org.

Learn More +

Protecting Pancreatic Islet Cells Following Transplantation for T1D

One of the challenges researchers have faced in developing long-term treatment options for type 1 diabetes (T1D) using allogeneic cells is that the body often rejects these cells. This means that patients would still need to take anti-rejection or immunosuppressant medications, which can be hard on the body and contribute to other issues. However, researchers may have found an option that protects cells while allowing them to control glucose levels.

In a new study, researchers encapsulated pancreatic islet cells with seven different alginate formulations and transplanted them into non-human primates. The goal was to maintain function of the cells without disruption by common challenges such as foreign-body response, pericapsular fibrotic overgrowth, or sedimentation of the microspheres. Of the seven alginates used, three showed transient islet graft function with decreased foreign-body response. One of the chemically modified microsphere formulations protected cells and glucose-response for four months without requiring immunosuppression.

This is a positive step toward correcting insulin deficiency using allogeneic cells. More research is necessary on the alginate formulations, and clinical trials have not yet been conducted in humans. The Diabetes Research Connection (DRC), though not involved in this trial, is interested to see where this study will lead and what it may mean for the future of T1D treatment options.

The DRC is committed to supporting T1D research and providing funding for early career scientists to carry out novel research projects. Learn more about current projects by visiting http://diabetesresearchconnection.org and consider donating to these efforts.

Learn More +

David Kindness wants to give back

“About a decade ago, when I was 15 years old, I was diagnosed with type 1 diabetes (T1D). It was really scary news. Overnight, doctors explained that I’d have to start counting carbs and managing carb intake, give myself insulin shots multiple times a day, and the scariest of all.. “There is no cure.” Since then, I’ve learned to manage it well. T1D graduated from college with me, it’s traveled internationally, gone on many hikes and road trips. It’s surfed, longboarded, rock climbed and skied with me, and it’s affected every step in the process of my life. As I’ve taught myself adventure photography in recent years, T1D has been behind the lens of every shot I’ve taken. Today, a decade after my diagnosis, I believe that a permanent cure for diabetes could be found within the next decade, from research. I want to use something I love – my photography – to help fund that research, so I’m donating a percentage of all proceeds from sales of both printed and digital photography to the search for a cure for type 1 diabetes.”

Learn More +

Qualifying for Social Security Benefits With Diabetes Complications

Guest Post by Disability Benefits Help

If you’re unable to manage your diabetes with lifestyle changes and medication, you may be eligible for assistance. The Social Security Administration (SSA) offers monthly disability benefits for people who are unable to work due to an illness or injury that will last for at least 12 months. While it is challenging to qualify with diabetes, those with significant complications may be eligible for help.

Medical Eligibility Via the Blue Book

The SSA uses its own medical guidebook of eligibility criteria, known colloquially as the Blue Book, when deeming eligibility status. Diabetes is not listed as a disabling condition in the Blue Book, but some of its complications are. Here are a couple of listings you may be able to qualify under:

Amputation

An amputation alone also will not qualify for disability benefits, but you will be eligible if you can meet any one of the following criteria:

  • You have both hands amputated
  • You have two limbs amputated but you’re unable to walk without use of two crutches, a walker, or a wheelchair
  • You have an amputation at the hip

If your mobility is severely limited, you should be able to qualify under the amputation listing. Keep in mind that this listing is for people who are unable to successfully use artificial limbs. If you’re able to walk with an artificial limb, you will not qualify here.

Neuropathy

Neuropathy will also qualify under the Blue Book. The first listing states that you’ll be eligible if you have neuropathy in at least two limbs and it makes it impossible for you to either stand from a seated position, balance while standing upright, or walk without using crutches, a walker, or a wheelchair.

If you still have some mobility but it’s affecting your ability to work, you will also qualify if you have significant difficulty with any one of the following areas of intellectual function:

  • Understanding, remembering, and applying information
  • Interacting with others in a work setting
  • Concentrating and completing tasks
  • “Adapting oneself,” which means controlling emotions in a work setting

The entire Blue Book can be found online, so you can review it with your doctor to determine if you qualify. There are dozens of listings that may be relevant for people with diabetes, including cardiovascular disorders, additional mobility problems, and more.

Starting Your Application

The easiest way to apply for disability is online on the SSA’s website. If you’d prefer, you can also apply in person with the assistance from a Social Security representative. Call the SSA toll free at 1-800-772-1213 to make an appointment to apply in person at your closest SSA office.

It should take three to five months to hear back from the SSA regarding your claim. The more disabilities and complications of diabetes you list on your application, the better your odds of approval.

Resources:

Learn More +

FDA Approval of Insulin Pump with Basal-IQ™ Technology Increases Options for T1D Patients

There is a plethora of options when it comes to managing type 1 diabetes. Some people don’t mind the finger sticks and calculation of insulin dosages, while others prefer to have everything automated for better monitoring and control. As technology changes and research improves, so do the devices used to treat T1D, which can make the process easier and less stressful.

The FDA recently approved the t:slim X2™ Insulin Pump with Basal-IQ™ technology by Tandem Diabetes Care®, Inc., and it is expected to be available in August 2018. This device is an automated insulin delivery system, but it has the ability to work with integrated continuous glucose monitoring (iCGM) systems and can automatically suspend insulin delivery when low glucose levels are predicted. The Basal-IQ technology can predict glucose levels up to 30 minutes in advance and respond accordingly. Once glucose rises, it once again begins administering insulin.

Patients who have the Dexcom G6® CGM will be able to use this device in conjunction with it. During the study, participants had a 31 percent reduction in the amount of time their blood sugar levels were at 70 mg/dL or lower. In addition, they experienced no rebound hyperglycemia thanks to the Basal-IQ technology.

Patients are in control of how they use the system and can turn the Basal-IQ feature on or off depending on their preference. They can also use the touchscreen system to display a CGM chart or simply the Bolus and Option buttons. Plus, they can customize the alerts received for highs and lows or insulin delivery being turned on or off. Furthermore, when integrated with the Dexcom G6 CGM, there are no finger sticks required to calibrate the system or determine dosing at mealtimes thanks to the Basal-IQ technology.

The Diabetes Research Connection (DRC) is excited to see new technology being developed and approved in order to improve quality of life and diabetes management for individuals with T1D. The organization strives to support continued advancement in the field through funding early career scientists conducting peer-reviewed studies. To learn more about current projects and find out how you can help, visit http://drcnew.awp.uxtesting.net.

Learn More +

New Technology May Mean Longer Lasting CGM Sensors

If you have ever used a continuous glucose monitoring (CGM) system to manage type 1 diabetes (T1D), you know that the glucose sensors typically only last a few days before they must be replaced. This can be an annoying yet necessary part of ensuring accurate results and effectively managing blood sugar levels. However, Senseonics recently received approval from the FDA on its Premarket Approval (PMA) application for a device containing a sensor that lasts up to three months before needing to be replaced.

The Eversense® CGM system is the only one to offer this continuous long-term monitoring. Rather than patients inserting the sensor themselves, it is implanted subcutaneously in the upper arm by a physician as an in-office procedure. This can help to alleviate the concern that individuals may have about doing it themselves or experiencing discomfort while wearing the sensor.

CGM systems can greatly improve diabetes management, but unfortunately, many people still are not taking advantage of this technology either because it is not available to them, they are concerned about the accuracy of the system, or they do not wear it as consistently as they should. Since this new system uses a sensor that lasts for up to three months, it eliminates the need to regularly change out sensors. Plus, the transmitter used to relay information is easily recharged without having to change sensors, and it works using Bluetooth technology. It also offers discreet on-body vibrations to give users alerts. CGM systems have been shown to decrease the risk of severe hypoglycemia and improve glucose control in individuals with T1D.

The Diabetes Research Connection (DRC) is interested to see how long-term sensors impact CGM use and management of T1D. The DRC is committed to supporting advancements in the treatment and prevention of T1D as well as improved quality of life for individuals living with the disease. That is why the organization provides valuable funding for early career scientists to conduct peer-reviewed, novel research studies for T1D. Check out current projects and learn how you can help by visiting http://drcnew.awp.uxtesting.net.

Learn More +

Metformin May Support Insulin Therapy for Type 1 Diabetes

Managing diabetes can be a very tedious process. Individuals must be vigilant about monitoring diet and exercise and how it affects their blood glucose levels. Insulin must be correctly dosed and administered to counteract these effects. Even with careful tracking, some individuals still have difficulty managing their type 1 diabetes and develop insulin resistance, metabolic syndrome, and other complications.

Typically metformin is a medication prescribed for those with pre-diabetes or type 2 diabetes to increase insulin sensitivity and insulin action. However, a recent study examined the effects of combining metformin with insulin therapy to treat individuals with type 1 diabetes who had poorly controlled blood glucose levels despite intensive insulin therapy. The study was small, involving 58 individuals with T1D who had comparable characteristics in terms of age, sex, BMI, blood pressure, lipids, hypertension, body weight, insulin dose requirement, duration of diabetes, and other factors.

Twenty-nine participants continued to receive insulin therapy alone, while the other 29 received a combination of metformin and insulin therapy. The study, which lasted one year, found that those in the metformin-insulin group required a lower dose of insulin after one year (a decrease of 0.03 IU/kg/d) compared to those in the insulin only group who actually required a higher dose of insulin (an increase of 0.11 IU/kg/d).  The metformin-insulin group also saw a decrease in metabolic syndrome prevalence, fasting plasma glucose (FPG), and postprandial plasma glucose (PPG) compared to the insulin only group.

A larger study is necessary to further evaluate long-term effects, glucose control, insulin sensitivity, and other factors related to effectively managing type 1 diabetes. However, the study sheds light on the potential benefits of combining metformin with insulin therapy for not just individuals with type 2 diabetes, but those with type 1 diabetes as well.

The Diabetes Research Connection (DRC) is interested to see what this could mean for future diabetes management strategies and approaches to helping those with poor glucose control despite intensive insulin therapy. The DRC supports novel research studies on type 1 diabetes by early-career scientists and provides critical funding for these projects. To learn more about current projects or find out how to help, visit Our Projects.

Learn More +

Insurance Gaps Put Individuals with Type 1 Diabetes at Increased Risk

Over the past few years, health insurance has gone through some major changes. Since type 1 diabetes requires constant monitoring and daily management with insulin, having insurance coverage is essential to help offset costs and promote effective self-care. A recent study found that individuals who experience gaps in private healthcare insurance coverage may be at greater risk for health crises.

The study involved data collected from approximately 169,000 adults with type 1 diabetes between the ages of 19 and 64 during the time period of early 2001 to mid-2015. Researchers evaluated this data and found that visits to the emergency room, hospital, or urgent care were five times more likely when patients regained coverage after a gap in insurance of 30 to 60 days. When the coverage gap expanded to 91 to 120 days, those individuals were seven times more likely to visit the emergency room, hospital, or urgent care.

These visits can be incredibly costly, but risk can be reduced with consistent insurance coverage and self-care under the direction of a physician. The study found that young adults – those in their 20s and 30s – were more likely to experience gaps in coverage than middle-aged and older adults. What part of the country individuals resided in played a role as well, with the north-central and southern parts of the United States seeing higher rates of gaps.

Since type 1 diabetes affects approximately 1.25 million Americans, it is essential that quality care and insurance coverage are available to support improved health and well-being and reduce the risk of preventable health crises.

The Diabetes Research Connection (DRC) is passionate about exploring various aspects of type 1 diabetes from prevention and treatment to potential cures and improved quality of life. The DRC provides valuable funding to support novel research studies regarding this condition. To learn more about current projects or donate to these efforts, visit Our Projects.

Learn More +

Exploring the Role of Microorganisms in Glucose Management

Although diabetes has been a topic of research for decades, there are still many unknowns. Researches are always discovering different elements that affect how the disease develops and is managed. Gut bacteria has been a recent area of interest, and researchers at the Salk Institute in La Jolla, California, have stumbled upon an interesting discovery.

While attempting to study the circadian rhythms of mouse metabolism following depletion of the mouse’s microbiome, they noticed something else intriguing: after being treated with antibiotics to kill off certain microorganisms, they found that the mice were able to more quickly and efficiently process glucose. The colon became enlarged as it took on a more prominent role in absorbing extra sugar, which decreased blood glucose levels. In addition, liver function changed as well, which affected metabolism.

Mice – and humans – all have a microbiome composed of a variety of microorganisms that all play a role in health. While some microbes put mice at greater risk of developing diabetes, some actually decrease this risk. The researchers are looking more closely at how certain bacteria affect the body and its function. They already know that ridding the body of bacteria has a significant impact on a mouse’s metabolism.

The scientists are now developing plans to study what elements in the microbiome affect liver function. According to Satchidananda Panda, senior author on the paper and a professor in the Regulatory Biology Laboratory at the Salk Institute, “Perhaps we could find ways to support the growth of certain gut microbes and induce these changes in glucose regulation in humans. We are now one step closer to translating this research.”

Though there is still a great deal of research that needs to be done before potential treatment options for diabetes emerge, it is a step in the right direction. The Diabetes Research Connection (DRC) follows the latest industry news to see what is on the horizon for diabetes care and treatment. The DRC contributes to advancements in research by providing funding for early career scientists pursuing novel research studies related to type 1 diabetes. Find out more about the organization and how to help by visiting Our Projects.

Learn More +

Medicare Implements Positive Changes to Policies for CGMs

Managing type 1 diabetes can be a difficult task. Individuals must constantly be aware of whether their blood glucose levels are rising, falling, or remaining stable. This has a significant impact on their well-being and quality of life. Many people have turned to continuous glucose monitors (CGMs) to help them track their blood glucose and adjust their insulin dosages and diet accordingly.

However, until January 2017, CGMs were not covered by Medicare, and even after new policies were rolled out at the start of the year, only certain devices were covered (the Dexcom G5 CGM and later the Abbott Freestyle Libre CGM). While this was a win for individuals with T1D who used these devices, there was a huge catch to the new policy: the CGMs could not be used in conjunction with smartphone applications. They had to be used solely with the provided data receiver. If the smartphone app was used, Medicare would not cover their supplies.

This was problematic because the app could be used to share information with family members, caregivers, and medical providers and allowed for closer tracking and monitoring of blood glucose levels. The app also provided helpful alerts and alarms so that users would know when their blood sugar was becoming too high or low and could respond accordingly.

After much lobbying and debate, the policy was finally changed in June 2018. Under the revised policy, individuals with CGMs are permitted to use the smartphone application in conjunction with the receiver and device. This is an important change because it means individuals have more options and flexibility in managing their diabetes and can share information as necessary.

The Diabetes Research Connection (DRC) acknowledges this as a step in the right direction toward making diabetes care more accessible and affordable and supporting data sharing to make more informed treatment-related decisions. T1D is a challenging disease, and researchers are learning more every day about causes, treatment options, and potential cures. The DRC supports early career scientists in conducting peer-reviewed novel research studies regarding T1D. To learn more, visit Our Projects.

Learn More +

Existing Medication May Be Beneficial in Treating and Preventing Type 1 Diabetes

A great deal of research has gone into better understanding type 1 diabetes and its potential causes. Many treatment options have been developed to support individuals in effectively managing their blood sugar whether through insulin, transplanted cells, or other means. Scientists are also always striving to create new options.

However, through some high-tech research, researchers may have found a way to treat and even possibly prevent type 1 diabetes using a medication that already exists and is approved by the Food and Drug Administration (FDA). Dr. Aaron Michels, an associate professor of medicine at the University of Colorado Anschutz Medical Campus in Aurora and his team found that more than half of individuals who are at risk for developing diabetes have the DQ8 molecule.

They believe that by blocking DQ8, they may be able to prevent the development of the disease and treat those patients already affected. Using a high-tech computer, they analyzed FDA-approved drugs for those that could be used to inhibit the DQ8 molecule. And it just so happens that one exists – methyldopa, a medication commonly used to treat high blood pressure. Unlike immune suppressant drugs which may be used to try to help manage T1D and can have undesirable side effects, methyldopa does not have a negative impact on the immune function of cells but still inhibits DQ8.

The researchers explored the potential of this drug using mice to confirm their findings, then conducted a small clinical study on 20 human participants with T1D with similar results. The results of their study may lead the way to more effective treatment and prevention of type 1 diabetes as well as other health conditions. They are set to conduct a larger clinical study to further investigate the use of methyldopa for T1D. According to Dr. Michels, “With this drug, we can potentially prevent up to 60 percent of type 1 diabetes in those at risk for the disease. This is a very significant development.”

The Diabetes Research Connection (DRC) is excited to see where this study may lead and how it may impact future treatment and prevention efforts for the disease. It could open doors to other studies on personalized treatment at the molecular level. Though not involved in this study, the DRC supports peer-reviewed novel research projects by early-career scientists focused on type 1 diabetes. To learn more about current projects and how to support these efforts, visit Our Projects.

Learn More +
Treating Type 1 Diabetes

Gene Therapy Targets Pancreatic Cells in Treating Type 1 Diabetes

A major challenge in treating type 1 diabetes is figuring out how to overcome the destruction of insulin-producing beta cells. The body mistakenly targets and destroys these cells leaving the body unable to manage blood sugar levels on its own. Individuals with this disease must be vigilant about checking their blood sugar and administering insulin as needed, which can be an exhausting task.

Current treatment options include injection of insulin, use of continuous glucose monitors and insulin pumps, stem cell therapies and implants, partial transplants, and other strategies. These treatments vary in effectiveness from person to person as well as how long they last. In addition, some require patients to continue taking anti-rejection drugs which can be hard on the body.

However, a new treatment may offer longer lasting, more effective results in the battle against type 1 diabetes. A recent study found that by using gene therapy targeting two specific genes, insulin-producing cells may be able to be recreated in the body using existing alpha cells. A healthy pancreas contains both alpha and beta cells. In those with type 1 diabetes, insulin-producing beta cells are destroyed. But when mice were injected with gene therapy to reprogram some alpha cells to take over the function of these beta cells, they were once again able to produce insulin and manage blood sugar.

The genetic changes were administered using a bioengineered virus. The virus had been altered so that it would not make the recipient ill, but could still penetrate cells to modify their DNA. The alpha cells then assumed insulin-producing functions without triggering the immune system to attack because the cells are already normally present in the body. Furthermore, researchers found that by delivering the gene therapy endoscopically into the pancreas, it stayed there and did not negatively impact other areas of the body.

While the treatment only lasted approximately four months in mice, scientists believe that it could be effective for several years in humans before retreatment would be necessary. The researchers are seeking FDA approval to begin clinical trials on humans using this gene therapy to evaluate its effectiveness and safety in treating type 1 and type 2 diabetes. There are approximately 30.3 million people in the United States and 422 million people worldwide affected by diabetes.

The Diabetes Research Connection (DRC) is excited to see how gene therapy may advance treatment options for type 1 diabetes and improve quality of life for millions of people. The DRC supports novel research studies for type 1 diabetes and provides essential funding early career scientists to carry out these studies. To learn more about current projects and donate to this research, visit Our Projects.

Learn More +

Advanced Technology Could Bypass Finger Sticks for Glucose Monitoring

One of the annoying – but necessary – parts of managing type 1 diabetes in conducting multiple finger sticks every day to check blood sugar levels. This is one of the most accurate ways that people with diabetes can determine whether they need to inject themselves with insulin or not, especially around mealtimes and when being physically active. But advances in technology may have found a way to accurately monitor blood sugar levels without requiring finger sticks.

Dexcom is a company that is well known for its continuous glucose monitoring (CGM) systems, and they are set to launch a new model, the Dexcom G6, in June. Ahead of this release, one user got to try it out early and shared her experiences with the new system.

The G6 comes with a sensor that is placed under the skin and affixed with a transmitter that wirelessly relays information to a receiver. The receiver is often the person’s smartphone and is accessed using a corresponding app. There is an auto-applicator that makes inserting the sensor quick, easy, and painless. Once inserted, it is functional for 10 days before shutting off and needing to be replaced.

However, the sensor continuously monitors blood sugar levels so that individuals do not have to constantly check on their own using a glucometer. For this user, it took a few days for the G6 to begin accurately reading her glucose levels, so she did double-check initially with the glucometer. However, soon they began giving the same readings, and she could track her blood sugar using the app.

The system also gives alerts and alarms for when blood sugar becomes too high or dips too low. It can even alert to downward trends before blood sugar gets the chance to become dangerously low, allowing individuals to appropriately respond and keep levels more stable. In addition, the company has made the transmitter sleeker and more comfortable. It has a 28% lower profile than the current G5 model and affixes flush against the sensor.

Since the system has not been released to the public yet, the final cost is unknown. Plus, this will vary depending on an individual’s insurance coverage or if they are paying out of pocket. However, it provides many benefits in helping individuals with T1D in effectively managing their blood sugar in a more hands-free way and providing readings around the clock that can be viewed through the app or receiver. The benefits may outweigh the costs in the end for some.

The Diabetes Research Connection (DRC) is excited to see how technology is changing to better support the needs of individuals with type 1 diabetes and help them manage their condition. As research continues to advance, so do technology and treatment options. The DRC is committed to empowering early career scientists in pursuing novel research around type 1 diabetes and raises funds to support these efforts. To learn more about current projects and provide support, visit http://diabetesresearchconnection.org.

Learn More +

Connecting For A Cure: June 2018 Newsletter

We’re committed to keeping our community updated on all projects and DRC happenings. Click on the link below to read more about what we’ve been up to this year and the impact we are making together. We believe it takes a community to connect for a cure and will continue supporting innovative scientific inquiry until diabetes is eliminated.
newsletter

Learn More +

Improved Blood Flow in Pancreatic Islet Cells May Help Treat Diabetes

Pancreatic islet cells play an essential role in managing blood glucose levels. These are the cells that produce insulin and control blood sugar. However, they require strong blood vessels and blood flow to work effectively. One of the challenges of trying to transplant these cells is that they lose blood vessels in the process.

Scientists mainly from Yokohama City University may have found a way to overcome this issue and improve the efficacy of transplanted pancreatic islet cells. To improve blood flow, they cultured pancreatic islet tissue with both endothelial cells and mesenchymal stem cells. Endothelial cells are what line blood vessels and mesenchymal stem cells have the ability to develop into different types of cells. This combination led to pancreatic islet tissue that contained its own network of blood vessels.

When transplanted into mice with severe type 1 diabetes, the tissue allowed for a strong blood flow which in turn helped to better control blood glucose levels. More than 90% of diabetic mice implanted with this tissue survived for at least five days. The diabetic mice who only received pancreatic islet cells but not the tissue with the blood vessel network only had a survival rate of around 40%. And in those mice who did not receive any type of transplant, nearly all passed away.

The scientists are in the process of expanding their research beyond the use of endothelial and mesenchymal stem cells to exploring the potential of human induced pluripotent stem (iPS) cells. They are hopeful that this will lead to another treatment option for individuals with type 1 diabetes.

The Diabetes Research Connection (DRC) is excited to see how this research progresses and the results it yields in terms of treating and managing type 1 diabetes. While not involved with this particular study, the DRC supports early career scientists in pursuing peer-reviewed, novel research projects geared toward the treatment, prevention, and cure of type 1 diabetes, as well as improving quality of life for those living with the disease. To learn more and support these efforts, visit http://diabetesresearchconnection.org.

Learn More +

Bystander T Cells May Play A More Active Role in Managing Type 1 Diabetes

There are many types of cells that all play a different role in how the body works. Some of these cell functions are very well known, while others are still somewhat mysterious. For years, scientists have thought that bystander T cells were just that – bystanders, since it was unclear what their exact purpose was. A team of researchers led by Matthias von Herrath, M.D., a professor in the La Jolla Institute for Allergy and Immunology’s Division of Developmental Immunology and a diabetes researcher, may have shed more light on what these cells actually do.

von Herrath and his team found that while the initial belief was that bystander T cells increased inflammation associated with type 1 diabetes and the destruction of insulin-producing islet cells, they may actually do quite the opposite. They found that these cells interfere with the destruction of pancreatic beta cells rather than supporting it. CD8+ cytotoxic T lymphocytes (CLTs) target specific protein fragments in islet cells and then destroy the cells. During this process, the pancreata are flooded with other T cells that do not detect protein fragments, which are referred to as the bystander T cells.

New studies by von Herrath and his team have discovered that in mouse models, the bystander T cells actually have an immunosuppressive effect and decrease the effect of cell-killing CLTs. When mice were injected with equal amounts of cell-killing and bystander CLTs, the researchers found that there was “little cell death, and the specific CLTs recruited to the pancreas became less harmful.” When decreased amounts of bystander cells were injected, there was more cell destruction as well as the occurrence of diabetes symptoms including hyperglycemia. Two possible theories are that bystander T cells limit access to beta cells as they flood the cell protecting them from cell-killing CLTs, or possibly that the bystanders interfered with the signals sent to cell-killing CLTs, so, therefore, the destruction is not as severe.

The study demonstrates that regulatory T cells are not the only cells that help counteract inflammation, though they are the most widely recognized for having this effect. With this new insight into bystander T cells, researchers may be able to leverage them in future treatment for type 1 diabetes. Additional research is necessary to explore this potential.

The Diabetes Research Connection, for which von Herrath is a member of the Scientific Review Committee, is committed to supporting novel research studies for type 1 diabetes. The DRC provides funding to support early career scientists in carrying out research projects geared toward preventing and curing type 1 diabetes as well as minimizing complications and improving quality of life for those living with the disease. Learn more about current projects and how to support these efforts by visiting http://diabetesresearchconnection.org.

Learn More +

Breaking Down the Prevalence of Type 1 Diabetes

Diabetes affects people of all ages and races throughout the United States, but just how many people are impacted? According to a self-report study of 33,028 adults with a response rate of 54.3%, approximately 21 million adults (8.6%) in the United States were living with type 2 diabetes in 2016, and approximately 1.3 million (0.55%) were living with type 1 diabetes.

The study, conducted by the Centers for Disease Control and Prevention (CDC) asked participants a variety of questions regarding being diagnosed with diabetes and what methods were used to manage it. Responses were classified as type 1, type 2, or “other” type of diabetes. There were 182 participants who reported having type 1 diabetes but did not claim to take any type of insulin, so they were categorized as type 2 respondents. Out of the 33,028 participants, 3,519 reported having diabetes, and 211 of those reported having type 1 diabetes. The study also found that T1D was more prevalent in men than women (0.64% vs. 0.46%), and as well as in non-Hispanic whites versus Hispanics (0.67% and 0.22% respectively).

Study authors hope that “knowledge about national prevalence of type 1 and type 2 diabetes might facilitate assessment of the long-term cost-effectiveness of public health interventions and policies aimed at improving diabetes management and help to prioritize national plans for future type-specific health services.”

Though it may seem like a small percentage who have T1D, it is still more than a million people who struggle each day with this disease, and more than a million people who would benefit from advanced research and treatment options. The Diabetes Research Connection seeks to further knowledge, research, and interventions regarding type 1 diabetes as well and supports novel research studies focused on this condition. Early career scientists can receive valuable funding through the DRC to support their research projects. Check out the current studies and support these efforts by visiting http://diabetesresearchconnection.org.

Learn More +

Are Artificial Pancreas Systems Effective in Treating Type 1 Diabetes?

There are many options available for treating type 1 diabetes from regular finger pricks and injections of insulin to continuous glucose monitoring systems to artificial pancreases and more. However, each person must find what works best for them in the management of their disease.

One treatment method that has undergone recent study is the use of artificial pancreas systems. According to researchers led by Eleni Bekiari, MD, Ph.D., at the Clinical Research and Evidence-Based Medicine Unit at the Aristotle University of Thessaloniki in Greece, these systems can provide positive results for some patients in managing their T1D. Throughout a series of 40 studies encompassing 1027 participants, artificial pancreas systems were found to not only be safe but also an effective line of treatment.

The study compared several different factors of single and dual hormone systems but mainly focused on the percentage of time normal glycemic levels were maintained. These results were measured against patients using standard insulin-based treatments. The study found that those individuals using the artificial pancreas systems experienced higher durations of time where their blood sugar levels were in the normoglycemic range, including overnight – 15.15% for artificial pancreas systems versus 9.62% for insulin-based treatment. There was also less deviation between blood sugar levels.

The researchers found that “artificial pancreas systems are an efficacious and safe approach for treating outpatients with type 1 diabetes.” More research and clinical trials are necessary to further explore the benefits and long-term outcomes of these systems. The Diabetes Research Connection is committed to supporting early career scientists in advancing their research and delving more deeply into topics related to the diagnosis, treatment, and management of type 1 diabetes. The DRC provides essential funding for researchers to carry out peer-reviewed, novel research projects. To learn more about current projects and support these efforts, visit http://diabetesresearchconnection.org.

Learn More +

Viruses May Cause T1D and Other Autoimmune Diseases

Viruses are the cause of many health conditions and affect the body in different ways. As scientists learn more about these viruses, they can develop targeted strategies for preventing and treating them. A major breakthrough was recently discovered involving a very common virus known as the Epstein-Barr Virus or EBV.

EBV is most commonly known for causing mononucleosis (mono) or the “kissing disease” since it is often transmitted via saliva. By age 20, more than 90 percent of the population in developed countries will be infected by the disease. This rate spikes in under-developed countries with more than 90 percent of the population being affected by age 2. There is no cure for the virus – it remains in the body for life, though may not have a noticeable impact.

However, researchers have found that the effect it can have at a cellular level may be more significant than previously realized. Scientists from the Cincinnati Children’s Hospital’s Center for Autoimmune Genomics and Etiology have published a study potentially linking EBV to seven diseases, including T1D. One of the Diabetes Research Connection’s own Scientific Review Committee members, Matthias Von Herrath, was an author on an article cited by the study in its research.

Typically, the body responds to viruses by increasing the production of antibodies by B cells. These antibodies then attack and destroy the virus. However, with EBV, the virus actually takes over the B cells and re-programs them using transcription factors. This alters the way that B cells respond and can change their basic function, which may increase the risk of developing other diseases. The scientists have narrowed it down to one factor in particular – the EBNA2 protein.

Transcription factors associated with this protein attach to and change sections of person’s genetic code. Depending on where they attach, it could contribute to different diseases including T1D, lupus, multiple sclerosis, rheumatoid arthritis, celiac disease, and more. Identifying what is happening on a cellular level could help researchers to develop more targeted treatment options and potential cures for these diseases. The study also opens doors for more in-depth research regarding how transcription factors may affect other gene variants and diseases.

These findings are very encouraging in better understanding some of the underlying factors that may contribute to T1D. More research is necessary to explore each disease in particular and the potential impact from EBV and the EBNA2 protein. The Diabetes Research Connection is excited to see where these discoveries may lead moving forward and how it could change the future of T1D treatment. The DRC provides funding to early-career scientists pursuing novel research studies on type 1 diabetes to improve prevention strategies, treatment options, and management techniques as well as potentially find a cure. Learn more about current projects and provide support by visiting http://diabetesresearchconnection.org.

Learn More +

Oxygen Supply May be Key in Supporting Islet Transplantation

One of the strategies scientists have focused on in the treatment of type 1 diabetes is transplanting healthy islet cells into the body to naturally produce insulin and manage blood glucose levels. These cells may be lab-generated or come from a donor. However, a major challenge has been conducting these transplants without reliance on immunosuppressants which can compromise overall patient health and complicate treatment.

In order to overcome this obstacle, researchers have created encapsulation devices to protect transplanted islet cells from attack by the body without using immunosuppressants. But with these devices, the lifespan of cells has been limited, in part due to poor oxygen supply. The devices often limit access to oxygen or restrict diffusion.

A new study has found that surrounding islet cells in an oxygen-permeable membrane and equipping the encapsulation device with an oxygen chamber can provide the necessary oxygen supply to keep cells functional and viable. Scientists experimented with varying levels of islet cell surface density and oxygen partial pressure (pO2).  The chamber allowed oxygen to be diffused throughout the highly concentrated alginate slab of islet cells.

The results showed that an average of 88% of islet cells maintained their viability and supported normoglycemic levels when tested in diabetic rats. Due to the continuous diffusion of oxygen, the chamber needs to be refilled daily through a subcutaneous port. Of the 137 rats in the trial, 66 remained normoglycemic for at least eight weeks. Some remained normoglycemic for up to 238 days, at which point the device was electively removed. Upon explanation, rats experienced hyperglycemia. When given intravenous glucose tolerance tests, results from rats with the implanted device were not significantly different than those of non-diabetic rats.

Researchers are currently exploring opportunities to decrease the size of the device while achieving greater islet density and continued viability. This study demonstrates how technology is advancing to create more options for treating and potentially curing type 1 diabetes with fewer complications and undesirable side effects.

Though not involved with this particular study, the Diabetes Research Connection is committed to supporting novel research for type 1 diabetes in an effort to prevent and cure the disease as well as reduce complications and improve quality of life for those living with type 1 diabetes. Visit us online at http://diabetesresearchconnection.org to learn more about current research projects and provide support for these initiatives.

Learn More +

National Tell A Story Day: A Founder’s Story

At the age of six, I knew something wasn’t quite right. I didn’t have the same energy as all the other kids did that I played with. My mom took me to the doctor and after running a few tests, the doctor says to my mom and me, “David has Type 1 Diabetes and won’t live past the age of 30”. We were devasted. Trying to comprehend and make sense of what my diagnosis actually meant at age 6 was impossible. There were no support systems in place back then. Not for me and not for my family.

It was 1960 and the management of T1D was in the “Stone Age”. I remember having to sharpen my own needles at home with a grinding stone, so I could inject myself with animal insulin that gave me horrible welts, it was extremely painful. To monitor my blood sugar, my mom would drive me to the hospital once a quarter to test through a urine sample.

Today, my blood is tested 288 times a day through a monitor. Those needles that I had to sharpen myself, have been replaced with an insulin pen. And, I proved those doctor’s wrong, I’m now in my 60’s, well past the age of 30. While recalling my journey with this disease, I realized that the time lapse between then and now is 50 years – an entire generation.

When I think about all of the advancements that have been made, how far we have come in 50 years, I’m amazed. In one generation, Genentech discovered how to synthesize human insulin. The accuracy of glucose testing has improved drastically. Blood glucose monitors now allow us to monitor at home. While researchers have not found a cure yet, in their search for one, they have found ways to improve the lives of those of us living with this extremely difficult disease and I for one, am forever grateful.

Imagine if today, the 1.3 million people affected by this disease were still having to inject themselves with animal insulin? This is why funding research is so important and why I founded the Diabetes Research Connection. To offer hope and advancements and one day, a cure.

Find out more about the Diabetes Research Connection (DRC) and how to support our efforts by visiting http://drcnew.awp.uxtesting.net/join-us/

Learn More +

What You Need to Know About Hypoglycemia Unawareness

Many people are aware of warning signs that their blood sugar is too low. They experience sweating, shakiness, hunger, or dizziness. They may also feel confused, sleepy, or weak. As a result, they eat or drink something to bring their blood sugar back up. However, some people with diabetes are unaware of the signs of hypoglycemia or low blood sugar – not that they don’t know what the symptoms are, they just don’t experience or perceive them. This can be dangerous to their health and well-being.

There are numerous risk factors for hypoglycemia including:

  • Sleeping: Blood sugar may drop while sleeping and occur frequently enough that it alters their ability to detect symptoms while awake.
  • Time: The longer someone lives with diabetes, the less sensitive they may become to low blood sugar. People who have used insulin for 20 years or more tend to be at greater risk.
  • Age: Older adults may experience cognitive changes that affect their ability to recognize hypoglycemia.
  • Exercise: Rigorous exercise can affect blood sugar levels up to 15 hours later.
  • Alcohol: When the liver is occupied with processing alcohol, it may not be able to release glucose as effectively resulting in hypoglycemia.
  • Prescription Drugs: Certain medications may affect a person’s ability to recognize symptoms of low blood sugar.

However, there are several ways to manage hypoglycemia unawareness and be proactive in keeping blood sugar in check.

  • Testing blood sugar more frequently throughout the day can help individuals to recognize when their blood sugar is getting low so they can treat it early.
  • Using a continuous glucose monitoring system (CGM) or automatic insulin delivery (AID) device can help with tracking blood sugar trends and administering or suspending insulin as necessary. This can help to achieve more stable blood glucose levels and reduce incidences of hypoglycemia.
  • Using long-acting or fast-acting insulin analogs may help as well, especially at night and during meal times.
  • Targeted training on improved insulin usage and how to be proactive in managing blood sugar can reduce risk. Working with a certified diabetes educator can be very beneficial in managing hypoglycemia unawareness.

Effectively managing blood sugar is an essential part of living with type 1 diabetes, but that can be difficult, especially with so many contributing factors and the fact that every person is different. That is what makes the work of the Diabetes Research Connection (DRC) even more important. The DRC provides vital funding for early career scientists to pursue novel research projects geared toward diagnosing, treating, and curing type 1 diabetes, as well as improving quality of life for individuals living with the disease. Their studies have the potential to make a difference in the future of type 1 diabetes care. Find out more about current projects and how to support these efforts by visiting http://diabetesresearchconnection.org.

Learn More +

Examining the Impact of Adding SGLT2 Inhibitors to T1D Treatment

For individuals living with type 1 diabetes, every day consists of checking their blood glucose levels, monitoring what they eat, and taking the appropriate amount of insulin to keep their blood sugar levels stable. However, long-term use of insulin can lead to undesirable dose-dependent side effects such as weight gain and hypoglycemia. Since there is currently no cure for T1D, these effects can be concerning because individuals must continue to take insulin for the foreseeable future.

Looking for a way to curb these effects, a recent study examined the efficacy of adding sodium-glucose cotransporter 2 inhibitors (SGLT2) to treatment for T1D. The medications used for the study were canagliflozin, empagliflozin, sotagliflozin, and dapagliflozin. Four different randomized controlled trials were conducted.

The results showed numerous positive changes when insulin use was combined with one of the four medications. There were statistically significant reductions in A1c levels as well as weight gain. In addition, the amount of insulin needed also decreased. While each medication led to different results, they all had similar effects on reducing these issues. Furthermore, the addition of these medications to treatment did not lead to any significant changes in risk associated with hypoglycemia, adverse events, or episodes of DKA.

This was a small study, so more extensive testing is necessary to evaluate the effects of SGLT2 inhibitors on T1D treatment on a larger scale. However, these initial tests show promising results and support for conducting more thorough investigations.

It is these types of forward-thinking research studies aimed at improving treatment and quality life for individuals living with T1D that the Diabetes Research Connection (DRC) is passionate about supporting. Though not involved in this study, the DRC has supported dozens of early career scientists by providing funding for novel research. These studies may lead to new breakthroughs or areas that can continue to be explored more deeply. To learn more about current projects and support these efforts, visit http://diabetesresearchconnection.org.

Learn More +

Could Real-Time Continuous Glucose Monitoring Reduce Incidences of Hypoglycemia?

Managing type 1 diabetes can be tricky. Many people rely on self-monitoring throughout the day by periodically testing their blood sugar and administering the proper dose of insulin as needed. Individuals with T1D often inject themselves with insulin multiple times per day. However, food, beverages, physical activity, illness, and other factors can all impact blood sugar levels making them more difficult to effectively manage.

But with advances in technology, continuous glucose monitoring (CGM) devices are now available to help those with T1D track and manage their blood sugar. These devices have a tiny sensor that is inserted under the skin which automatically measures blood glucose levels and transmits the information to a monitoring device. The system can also alert when blood sugar becomes too high or falls below a specified level allowing individuals to respond accordingly.

A recent study conducted across 12 diabetes centers in Germany aimed to determine whether the use of real-time CGM (rtCGM) systems could reduce the number and severity of incidences of hypoglycemia in patients with T1D who had a history of impaired hypoglycemia awareness or severe hypoglycemia within the previous 12 months. The study involved 149 participants, and 141 successfully completed the trial in its entirety.

All participants wore a masked rtCGM system for 28 days before being randomly assigned to one of two groups: the first group wore an unmasked rtCGM system for the next 26 weeks, and the second group was a control group that self-monitored blood glucose levels during this time. The results of the study found that the group that wore the rtCGM system had a 72% decrease in the number of hypoglycemic events (10.8 to 3.5 per 28 days), while the control group saw no significant reduction (14.4 to 13.7 per 28 days). Therefore, the rtCGM system was able to reduce the number of hypoglycemic events that occurred in individuals with a history of severe hypoglycemia or impaired hypoglycemia awareness.

The Diabetes Research Connection (DRC) is encouraged to see the difference these types of devices can make in the lives of individuals living with type 1 diabetes. It is through innovative research studies and technology development that these advances are possible. The DRC supports early career scientists in pursuing novel research geared toward diagnosing, treating, or curing T1D, as well as improving quality of life for those living with the disease. Learn more about the incredible projects that are taking place and find out how you can be a part of supporting these initiatives by visiting http://diabetesresearchconnection.org.

Learn More +

Key Control Factor in Regulating Blood Glucose Level Identified

Despite years of research, type 1 diabetes remains a complex disease without a definitive cure. However, researchers continue to make new discoveries in how the disease develops and impacts the body. This allows for more targeted approaches to treatment. One such recent discovery is pinpointing the mechanism that is believed to be primarily responsible for controlling blood glucose levels in humans.

Researchers at the Karolinska Institutet in Sweden and the University of Miami Miller School of Medicine in Florida have released a study that identifies pancreatic islets as the main control function. Though glucose homeostasis involves the liver, hypothalamus, and pancreas, it is the pancreatic islets which release hormones and insulin that appear to have the most influence in regulation.

Different animals have their own set point of what is a normal blood glucose range, including humans. The researchers transplanted pancreatic islets from different animals into mice with and without diabetes. According to Principal Investigator Per-Olof Berggren, a professor at the Rolf Luft Research Centre for Diabetes and Endocrinology at Karolinska Institutet’s Department of Molecular Medicine and Surgery, “We found that the engrafted islets transferred the glycemic levels of the donor species. This indicates that the pancreatic islets have the overall responsibility for maintaining normal blood glucose levels, making them the ‘glucostat’ in our bodies.”

Human pancreatic islets contain cells that release the hormone glucagon which regulates insulin-producing cells. This is an important discovery when it comes to developing treatment approaches because scientists may find that including these hormone-producing cells in addition to insulin-producing cells when creating artificial islets could be beneficial in better-regulating blood glucose levels.

It is these types of discoveries that enable researchers to develop more advanced and effective options for treating and potentially curing type 1 diabetes. The Diabetes Research Connection supports early career scientists in pursuing novel research projects aimed at diagnosing and treating type 1 diabetes as well as improving quality of life for individuals living with the disease. To learn more about their innovative research and contribute to its advancement, visit http://diabetesresearchconnection.org.

Learn More +

Improving PD-L1 Levels to Treat Type 1 Diabetes

A major obstacle that researchers face in treating type 1 diabetes (T1D) is the body’s own immune system. In individuals with T1D, the immune system destroys insulin-producing beta cells whether naturally occurring or introduced through novel therapeutic approaches. The use of anti-rejection drugs to protect newly injected or created cells can be hard to the body and contribute to undesirable side effects.

However, researchers at Boston Children’s Hospital are studying a new approach to treating – and potentially curing – T1D. They found that in individuals with T1D have a deficiency of PD-L1, a protein that helps prevent autoimmune reactions by binding to PD-1 receptors. By treating blood stem cells using gene therapy or a cocktail of small molecules, they were able to increase PD-L1 production. In turn, this helped to reverse hyperglycemia and better manage blood sugar levels.

In an experiment using mice with diabetes, “almost all the mice were cured of diabetes in the short term, and one-third maintained normal blood sugar levels for the duration of their lives.” In addition, the risk of adverse events is practically eliminated since the therapy uses the patients’ own cells. Though immunotherapies have been used before in an effort to treat T1D, they have not been targeted specifically for diabetes, whereas in this study, they are.

The research team has already met with the U.S. Food and Drug Administration for a pre-investigational new drug meeting regarding the combination of small-molecules used during the mouse trials in order to begin the approval process for human clinical trials.

This is an exciting step toward advancing treatment options for type 1 diabetes and potentially reversing the disease. More research is needed to determine how long the effects last and how often treatment would be needed.

The Diabetes Research Connection (DRC) is interested to see how the study progresses in the future and what it could mean for individuals living with type 1 diabetes. Though not involved with this particular project, the DRC supports early career scientists in pursuing novel research studies geared toward preventing, treating, and curing T1D, as well as improving quality of life for those living with the disease. Learn more about these researchers and their projects by visiting http://diabetesresearchconnection.org.

Learn More +

Exploring Beta Cell Regeneration in Treating Type 1 Diabetes

In individuals with type 1 diabetes (T1D), the body’s immune system mistakenly destroys insulin-producing beta cells necessary for managing blood sugar. Instead, patients must constantly monitor their own blood glucose levels and administer the proper dosage of insulin as necessary. In individuals without T1D, the pancreas does this automatically.

Some of the challenges that researchers have faced in trying to treat or cure T1D through cellular means is that the body may still reject these cells, there may be a shortage of donor cells, or the process of creating necessary beta cells can be complex. However, researchers at the Diabetes Research Institute at the University of Miami Miller School of Medicine may have found an effective way of using the body’s existing cell supply to generate insulin-producing beta cells.

The researchers identified the exact location in the body of progenitor cells with the ability to develop into beta cells. When stimulated by bone morphogenetic protein 7 (BMP-7), a naturally occurring growth factor, the pancreatic cells differentiated into the necessary beta cells. This discovery could lead to a significant supply of new beta cells within patients’ own bodies, eliminating the need for donor cells and curbing other immune-related challenges of treatment.

This process still requires more in-depth study, but it could lead the way to new regenerative medicine strategies that stimulate insulin production more naturally. The researchers are currently exploring options to reduce the need for lifelong anti-rejection drugs by enhancing immune tolerance of the newly created cells.

This study is another step toward advancing the treatment of T1D and providing patients with more options for care. The more scientists learn about the causes and effects of T1D, the more they can target approaches to treatment.

The Diabetes Research Connection (DRC) stays abreast of the latest developments in the field and encourages novel research projects by early-career scientists focused on T1D. The DRC raises funds through contributions by individuals, organizations, and foundations to support the advancement of these studies. Find out how you can get involved by visiting http://diabetesresearchconnection.org.

Learn More +

Could Implantable Glucose Sensors be a Viable Option for Monitoring Blood Sugar?

Diabetes management has come a long way over the years. Some people have transitioned away from constant finger pricks and begun using continuous glucose monitoring (CGM) systems to track their blood sugar and alert them to episodes of hyperglycemia or hypoglycemia. However, not everyone has the same level of adherence to using this technology, so results can be inconsistent.

Researchers from Diablo Clinical Research recently conducted a study on the use of implantable, subcutaneous continuous glucose sensors for diabetes management. A small sensor was placed under the skin, and then a transmitter was positioned over top providing wireless power and transmission of data to a mobile app. The transmitter also vibrated to alert users of episodes of hyper- or hypoglycemia in addition to alerts being sent to the app.

There were 90 adults with type 1 and type 2 diabetes who participated in the nonrandomized, prospective, masked, single-arm study which lasted for 90 days. Sixty-one of the participants had type 1 diabetes. Individuals underwent accuracy assessment visits on days 1, 30, 60, and 90 to compare results of the implantable sensor versus a bedside glucose analyzer. In addition, some participants also partook in hyperglycemia and hypoglycemia challenges on days 30, 60, and 90. There were only eight participants who did not complete the study, and 12 reports of mild adverse events and two moderate adverse events.

Following the study, the results showed “more than 90% of continuous glucose monitoring system readings within 20% of reference values.” Furthermore, “the system correctly identified 93% of hypoglycemic events and 96% of hyperglycemic events by the reference glucose reader.” The implantable CGM system used was Eversense by Senseonics.

Additional clinical studies are necessary to further evaluate the safety and accuracy of the system and expand potential use to pediatric patients as well. However, preliminary results show high levels of safety and accuracy in this small study.

This is an exciting step toward providing individuals with T1D another option for managing diabetes allowing them to measure blood sugar levels more consistently and with less intervention. The Diabetes Research Connection (DRC) is interested to see how this study advances moving forward and what it may mean for diabetes management in the future. The DRC raises funds for early career scientists to perform peer-reviewed, novel research designed to prevent and cure type 1 diabetes, minimize its complications, and improve quality of life for those living with the disease. To learn more and support these efforts, visit http://diabetesresearchconnection.org.

Learn More +

Could Viruses Play a Role in the Development of Type 1 Diabetes?

While researchers know that type 1 diabetes involves the destruction of insulin-producing beta cells or lack of production of insulin, they are still not clear on exactly what causes type 1 diabetes to develop. A great deal of time has been devoted to studying genetics and the role it may play in T1D risk. Now scientists are exploring a different avenue – the influence of viruses on diabetes risk.

A recent study led by Professor Ronald Kahn, chief academic officer at Joslin Diabetes Center, identified four viruses that can produce insulin-like hormones. These viruses were found to “produce peptides that are similar in whole or in part to 16 human hormones and regulatory proteins.” While these viruses are found in fish and amphibians, not humans, eating fish may expose the human body to the viruses and therefore have an effect.

Scientists synthesized these peptides and conducted experiments on mice and human cells to determine how they would respond. The viral insulin-like peptides (VILPs) acted like hormones, attached to human insulin receptors, and stimulated the same signaling pathways. In addition, mice were found to have lower levels of blood glucose after being exposed to the VILPs.

According to Kahn, these research findings could lead to new studies regarding type 1 diabetes and autoimmunity. The insulin-like hormones “could be an environmental trigger to start the autoimmune reaction in type 1 diabetes.” However, there is the possibility that they could work as a protective factor as well by desensitizing the immune response.

There are more than 300,000 viruses carried by mammals, but only about 7,500 have been sequenced so far, so there is the possibility that other viruses exist that may affect human cells and T1D risk as well. This study is just the start of understanding the role of microbes in human disease according to Dr. Emrah Altindis who also works at the Joslin Diabetes Center.

The depth and breadth of understanding regarding type 1 diabetes and various aspects of the disease is expanding every day. The Diabetes Research Connection is committed to supporting peer-reviewed, novel research studies that aim to improve diagnosis, treatment, and quality of life for individuals living with T1D.  Through donations from individuals, companies, and foundations, the DRC provides funding to early career scientists to pursue innovative projects. Learn more about current projects and how to support these efforts by visiting http://diabetesresearchconnection.org.

Learn More +

What is Up-and-Coming in Diabetes Technology?

A new year is underway, and with that comes the emergence of advances in diabetes technology. Companies like Tandem, Dexcom, Medtronic, Insulet, and Senseonics are continuing to move forward with projects that have been in the works for several years, as well as new ones. They are constantly striving to improve how diabetes is managed and to enhance the quality of life for those living with the disease.

Here are just a few of the technology changes in the works:

Closed loop systems. Many companies are still working to refine these processes. It is difficult to create an effective system that requires no user interaction, but they are getting closer. Currently, they are focused on reducing the amount of user input necessary and turning to sensor technology to measure and track blood glucose levels, automatically dose according to individual needs, and predict glucose levels. No fully closed loop systems are expected to be released in 2018, however.

Smartwatch and smartphone compatibility. Many people nowadays own smartphones and smartwatches. Companies are leveraging these connections to bring glucose monitoring right to people’s fingertips. With improved sensors and Bluetooth technology, data can be delivered directly to these devices through apps that allow for better tracking and monitoring of glucose levels. Users would also have the option of sharing this data with others, such as healthcare providers. There are a variety of apps in development with features to improve diabetes management.

Improved sensors. Speaking of sensors, they’re changing too. Industry leaders are looking to make sensors smaller yet more effective and accurate. They are also trying to extend the length of wear and reduce the number of daily calibrations needed. In turn, this would allow individuals more freedom and require less interaction with these systems while still managing blood sugar.

Increased FDA approval. There are some devices and technologies that are approved internationally but are not yet available in the United States. Or, approvals in the United States are stricter. International companies are looking to expand the availability of certain products in the U.S. and ensure that their diabetes care technology meets required standards.

Overall, there are numerous collaborations occurring between companies within the diabetes vertical that could have a positive impact on how the disease in managed moving forward. Companies are working together to bring about more advanced technology and monitoring systems that will make it easier for individuals to track not only their glucose levels, but also insulin use, meals, activity, and other factors that impact their diabetes care – and share it with their healthcare providers.

The Diabetes Research Connection is excited to learn more about these advancements in the months to come and see how diabetes care is changing for the future. The organization proudly supports novel research projects by early-career scientists and provides up to $50,000 in funding for studies. Learn more about current projects and how to support these initiatives by visiting http://diabetesresearchconnection.org.

Learn More +

Brain Differences May Impact Ability to Recognize Low Blood Sugar

Healthy adults can typically recognize when their blood sugar may be becoming too low. It triggers physical symptoms such as dizziness, sweating, weakness, and rapid heartbeat, just to name a few. Plus, their body responds by producing glucose and initiating the brain to signal for food. However, in individuals with type 1 diabetes, the brain does not always respond in this way.

A recent study found that the areas of the brain activated by low blood sugar in adults without diabetes are not the same as those in adults with type 1 diabetes. In brain scans of non-diabetic adults, areas associated with reward, motivation, and decision making showed changes during brain scans. However, only half of the individuals with T1D experienced similar changes, and only in one area of the brain – the area associated with attention – and the other half experienced no changes. Their brain showed no noticeable response to having low blood sugar, which is why individuals may miss cues that others would typically pick up on.

According to Janice Hwang, M.D., assistant professor of medicine and first author on the study, “There is a progressive loss of coordinated brain response to low blood sugar as you go from healthy adult to aware to unaware. The first areas of the brain to go are associated with feeding behavior.” The researchers are hoping that these findings will lead to more effective ways of restoring low blood sugar awareness in individuals with T1D who have lost this awareness.

It is these types of discoveries that help to improve understanding of how T1D affects the brain and body and allows researchers to develop more effective ways of treating and managing the condition. The Diabetes Research Connection supports early career scientists striving to advance research regarding the treatment, prevention, diagnosis, and management of T1D. Researchers can receive up to $50,000 in funding to apply toward their project. To learn more or support these efforts, visit http://diabetesresearchconnection.org.

Learn More +

DRC-Funded Scientist Creates New Insulin-Producing Cells to Fight Type 1 Diabetes

Thanks in part to funding from the Diabetes Research Connection (DRC), Dr. Kristin Mussar was able to conduct an in-depth study regarding how to stimulate the body’s own cells to create new insulin-producing cells that may help treat type 1 diabetes (T1D). In individuals with T1D, the immune system attacks insulin-producing cells, destroying them and leaving the body unable to effectively regulate blood sugar.

The human body is filled with myeloid cells that all differentiate to help grow, maintain, and repair various organs. When these cells are depleted, it impacts organ health. For instance, lack of insulin-producing cells results in diabetes. However, Dr. Mussar and her team discovered that there is a population of macrophages – white blood cells that recirculate throughout the body constantly monitoring the health status of all tissues – that instruct insulin-producing cells to grow in the perinatal stage of pancreas development. During this period of prolific growth, enough insulin-producing cells are created to support glucose homeostasis throughout one’s life.

Dr. Mussar found that there is a special population of these cells that act as cargos of potent growth factors for the insulin-producing cells in the pancreas. If these cells are prevented from entering the pancreas, the growth of insulin-producing cells is arrested and diabetes ensues. This lack of cell growth, as well as cell destruction, are issues that researchers have been trying to remedy through various strategies for treating T1D.

One avenue of treatment that is being explored is finding ways to use the body’s own cells and processes to support insulin production. Current challenges in treatment include the constant monitoring and accurate dosing of insulin, as well as the use of immunosuppressants or other medications to prevent the body from destroying modified cells or specialized therapies. Using the body’s own cells can help reduce risk of immune attack or rejection.

To this effect, Dr. Mussar’s research revealed that there are precursors to these special macrophages that exist within the bone marrow of adults. When these precursors are injected into the blood stream, they are able to signal growth of insulin-producing cells. This discovery raises hopes that, by dispatching these pro-regenerative cells from the bone marrow to injured pancreatic islets, it may be possible to enhance regeneration of insulin-producing cells in individuals with type 1 diabetes. This may in turn help to stabilize blood sugar naturally using the body’s own cells.

The Diabetes Research Connection is proud to have played a role in making Dr. Mussar’s research possible by providing funding that enabled her to continue moving forward with her project and eventually get the results published in the Journal of Clinical Investigation.

Learn More +

Could Reprogramming Cells Help Treat Type 1 Diabetes?

More than 300 million people around the world are living with diabetes. Currently, there is no cure, but scientists are continually researching and testing different methods for treating and managing this disease. One of the major obstacles faced in treating type 1 diabetes is that the body’s immune system attacks and destroys insulin-producing beta cells, whether these cells are naturally occurring or introduced through medical treatment.

Some researchers are looking at ways to reprogram the body’s own cells to function as insulin-producing cells to help better control blood sugar. The human pancreas contains small niches where hormone-making cells reside. Within these niches, two different cells predominate: alpha cells, which make glucagon, and beta cells, which make insulin. In individuals with type 1 diabetes, insulin-producing cells are destroyed, but glucagon cells are not.

Scientists developed a method using viruses as carriers to deliver two genes that are present in insulin but glucagon cells to the glucagon cells allowing the cells to be able to produce insulin. Glucagon cells are a good option for this process because they are similar to insulin cells and appear in abundance in islets within the pancreas already. A decrease in these cells as they were reprogrammed did not appear to affect glucose metabolism.

These experiments have been performed in NOD mice, which are mice that develop diabetes very close to human diabetes. Following the experiment, the diabetes disease appeared to have resolved in the diabetic NOD mice thanks to the new source of cells making insulin in their pancreas. However, human application of this technique will take time since targeting specific cells is complicated, and the use of viral elements creates side effects that need to be resolved.

It is this type of research and these experiments that lead to breakthroughs in the treatment, management, prevention, and improvement in the quality of life for individuals living with type 1 diabetes. Though not involved in this particular study, the Diabetes Research Connection supports early-career scientists through funding for novel research on type 1 diabetes. Learn more about current projects and support their advancement by visiting http://diabetesresearchconnection.org.

Learn More +

Is a New Transplant Site the Key to a Type 1 Diabetes Cure?

The Diabetes Research Connection is proud to partner with Beyond Type 1 to accelerate the most promising efforts for a cure for Type 1 diabetes. This is one of many projects we’re excited to partner on. Gifts start at $1 and 100% of your funds designated for research go directly to the lab. To date, $8,002 of a necessary $50,000 has been raised to move forward with this idea.

Have you heard about the handful of Diabetes Research Institute (DRI) patients that went without insulin for 10 years after cell replacement therapy? Their results showed that we can restore insulin production in those with Type 1 diabetes and that a biological cure is possible.

This treatment is not available (yet) to the millions with diabetes. While it was effective for some and improved their quality of life, the issue of cell survival and need for immunosuppressants post-transplant remains. Can a new location for the islet cell BioHub or “mini-organ” remedy these issues? The liver, the site used previously, has an adequate blood supply and is an easy-to-access location; however, it is the body’s filter for toxins, so the cells are exposed to waste, which decreases their longevity.

Dr. David Baidal at DRI believes that there may be a better location for cell replacement therapy: the omentum, a layer of fatty tissue that covers the organs in the lower abdomen. Like the liver, it’s close to the surface and is also highly vascularized. The big difference is it isn’t surrounded by waste and has an even larger surface area for scientists to work with.
DRI says there have been “encouraging preliminary results in animal models have demonstrated that islets in the omentum can engraft (become lodged in the tissue, get their own vessels and start producing insulin) and improve blood glucose control.”

With approval from the FDA, a new clinical trial is now underway in humans.

The Clinical Trail

The DRI BioHub is a bioengineered mini-organ designed to mimic the pancreas. “The islets are transplanted within a fully-resorbable (biodegradable) biologic scaffold consisting of the patient’s plasma (the liquid part of the blood that does not contain cells) and human thrombin, a clotting enzyme commonly used in surgical procedures,” explains DRC.

“The biologic scaffold will serve as a platform that adheres to the omentum and holds the islets in place. The patients in this clinical trial will require the same immunosuppressive (anti-rejection) drug regimen as used in islet transplants within the liver. However, our goal at the DRI is to eliminate the need for these drugs. The development of the DRI BioHub, together with several other areas of research strategies underway at the Institute, are aimed at overcoming challenges of the immune system.”

You can fund this project directly! Researchers have raised $8,000 of a necessary $50,000 to move forward with this idea. Let’s make it happen.

Learn More +

Scientists Delve More Deeply into Genetics and T1D

Type 1 diabetes is a complex disease. Scientists know that it is not caused by a single gene – there are multiple genes involved, and the differences may vary from person to person. In fact, a recent study by a TEDDY (The Environmental Determinants of Diabetes in the Young) team has identified six gene regions that may play a role in the development of type 1 diabetes (T1D).

Researchers have already found that there are two key antibodies that are present in individuals with the disease, but one typically appears before the other, and just because a person has one or both of these antibodies does not necessarily mean they will develop diabetes. These two antibodies – one that affects insulin and one that affects the enzyme that regulates insulin-producing beta cells – account for two major subtypes of the disease, and there may be more yet to be discovered.

This recent TEDDY study focused on identifying non-HLA genes because these genes are not directly linked to the immune system. Because the immune system attacks insulin-producing beta cells, HLA genes are already a prime focus, so the researchers wanted to look at a different area. The more genes that can be identified as potentially playing a role in type 1 diabetes risk, the more effective and accurate screening measures can be.

The TEDDY initiative looks at both genetic and environmental factors in diabetes to determine how they may impact one another. The international initiative is following nearly 9,000 children for 15 years. This particular study involved 5,806 Caucasian TEDDY participants due to genetic differences between ethnic groups.

In addition to examining non-HLA genes, the researchers also looked at 176,586 single nucleotide polymorphisms (SNPs), or single variations in the building blocks of an individual’s DNA. They sought to determine whether type 1 diabetes is associated with certain SNPs. They broke this down even further to look at differences in SNPs in individuals who have T1D, and those who have islet cell autoantibodies (IA). While IA is considered a risk factor, it does not always develop into full-blown T1D.

This is the first time that this type of longitudinal study has been used in conjunction with gene identification and the development of diabetes. Scientists are hopeful that by better understanding the genetic changes that occur with T1D, they can improve detection of risk factors and potentially develop new strategies for preventing or treating the disease. According to the National Institutes of Health, 1 in 300 people in the United States are affected by type 1 diabetes by age 18.

Supporting novel research that aims to prevent and cure type 1 diabetes, or improve quality of life and reduce complications for individuals living with the disease, is the aim of the Diabetes Research Connection (DRC). Though not associated with this particular project, the DRC provides funding for early career scientists to move forward with research studies on T1D and improve understanding of the disease. To learn more, visit http://diabetesresearchconnection.org.

Learn More +

Single Strand of Islet Cells Could Change Diabetes Management

For patients with type 1 diabetes, daily insulin injections become a way of life. Since the pancreas either does not produce enough or any insulin, and the body’s immune system destroys insulin-producing beta cells, the body is unable to regulate blood sugar on its own. There are many studies underway examining potential treatments that would eliminate the need for regular insulin injections.

One such study is being conducted by researchers at Cornell University in collaboration with Novo Nordisk and the University of Michigan Medical School. The researchers have developed an implant that would enable the production of insulin while warding off an attack from the immune system. The device is a single thread covered with “hundreds of thousands of islet cells” that is then fully encased in hydrogel. The hydrogel not only keeps the islets in place, it also protects them from being damaged.

The thread does not adhere to tissue within the body, so it can be easily removed and replaced once the islet cells reach the end of their lifespan. Current research shows they could potentially last anywhere from several months up to two years. This device has shown promising results when tested in both mice and dogs. No testing on humans has taken place yet, which would need to be done before the technology is potentially approved for use.

Technology continues to advance when it comes to treating and managing type 1 diabetes, and this is very encouraging. The Diabetes Research Connection strives to support early career scientists in conducting novel research studies focused on type 1 diabetes in order to improve the quality of life for individuals living with the disease and enhance diagnosis, prevention, and treatment efforts. To learn more, visit http://diabetesresearchconnection.org.

Learn More +

Patents Approved for Small Molecule Therapies for Type 1 Diabetes

There are numerous approaches to managing, treating, and potentially curing type 1 diabetes (T1D). Some focus on replenishing or protecting insulin-producing beta cells, some involve the development of devices that simulate similar functions, and still, others seek to zero in on issues related to the development of T1D.

ImmunoMolecular Therapeutics recently received patents for two of its small molecule therapies that can be used in the treatment of T1D. These patents provide exclusive rights to the use of methyldopa and D-methyldopa (D-MDOPA) as part of immunotherapy treatment. According to the company, “The lead candidate drug [D-MDOPA] is an oral small molecule that starves the autoimmune process in type 1 diabetes by blocking DQ8 on specific immune cells. Our goal is to preserve pancreatic beta cell function and maintain normal insulin production in at-risk and early-stage patients with type 1 diabetes.” By blocking DQ8, the immune system will not attack insulin-producing beta cells, therefore, preserving their function.

Immunotherapy is one option when it comes to treating T1D. The Diabetes Research Connection supports early career scientists in moving forward with novel research for a variety of methods used in the treatment and prevention of the disease. To learn more about current projects and support their advancement, visit http://diabetesresearchconnection.org.

Learn More +
Kristin-Mussar in a labcoat

Next-Generation Scientist Publishes Research Findings

One of DRC’s funded researchers, Kristin Mussar, Ph.D., completed her project and published findings in the Journal of Clinical Investigation.  Kristin’s research project set out to create new insulin-producing cells to repair a damaged pancreas. Her research found evidence that macrophages, a type of white cell that is usually associated with infections, also plays an important role in the development of islets, where insulin is made, just before and immediately after birth. The published report shows how macrophages help the islets grow indicating that selected agents may activate the cascade of proteins enhancing islet growth, an important contribution for future treatments in type 1 diabetes. Click here to read the full report.

Learn More +

Stem-Cell Derived Therapy for Type 1 Diabetes Funded to Move Forward

Scientists have been exploring many options for treating and potentially curing type 1 diabetes (T1D) in recent years. From examining the role of gut cells to creating an artificial pancreas, the studies have been diverse. Some challenges that they have faced are undesirable side effects, short-term effects, the need for immune suppression, and continued destruction of insulin-producing cells.

However, Semma Therapeutics recently secured $114 million in Series B financing to move forward with a program using encapsulated stem cell-derived islets to treat and potentially cure T1D. This financing was made possible through investments from multiple partners and investors. It will be used to advance the stem-cell derived therapy through clinical proof-of-concept in patients.

The technology and processes used by Semma have the ability to create billions of insulin-producing beta cells that perform in the same way these cells do when naturally produced by the body. However, these cells are combined with an innovative cell delivery technology that protects them from being destroyed by the body’s immune system. Ideally, this would enable them to continue regulating blood sugar while reducing the risk of complications and the need for constant blood sugar monitoring and insulin injections.

According to Semma Therapeutics Founder and Board Observer Douglas Melton, “Semma’s scientists have very effectively dedicated themselves to systems that reliably generate cells indistinguishable from human pancreatic beta cells and to the invention of novel devices that are immunologically protective and surgically practical. We’re very encouraged and excited about the potential this program has for diabetic patients and their families.”

The Diabetes Research Connection is eager to see how this program could impact the lives of those living with T1D, as well as the progress and direction of treatment options moving forward. The Diabetes Research Connection is not connected to this project, but raises funds to support early career scientists in conducting novel research in preventing, treating, and curing T1D, as well as improving quality of life for individuals with the disease. To learn more, visit http://diabetesresearchconnection.org.

Learn More +

How Technology is Changing Diabetes Care and Treatment

Despite years of research and clinical trials, no cure for type 1 diabetes exists yet. However, how the disease is managed and treated has changed, leading to vast improvements in quality of life. Many individuals are better able to track their blood sugar and administer insulin more effectively to reduce instances of hypoglycemia and other complications. A recent article explores how technology has impacted current research for type 1 diabetes.

For years, researchers were focused on developing immunotherapies to try to treat T1D at its source. With this type of diabetes, the immune system attacks and destroys insulin-producing beta cells from the pancreas. The goal was to either reverse the disease or stop it from developing in the first place. Today, researchers have shifted their focus. Instead of trying to figure out how to prevent diabetes, some scientists are working to improve how patients live with the disease. This has involved major leaps in medicine including attempts at developing an artificial pancreas system that would function similar to the body’s own pancreas to regulate blood sugar.

Over the years, researchers have experimented with a variety of immune therapies trying to find an approach that could treat diabetes without a host of unpleasant side effects. This has been a difficult process and not yet produced a significantly effective treatment. However, there have continued to be technological advances that have improved how patients manage diabetes. It is easier than ever to quickly test blood sugar, and some patients even have continuous glucose monitors that send information to their smartphone and alert to low blood sugar. There have also been many improvements in more accurate dosing and administering insulin.

In 2016, scientists made progress toward creating an “artificial pancreas” system. It combined a continuous glucose monitor and insulin pump to modulate insulin delivery based on data over time. It is not yet fully automated, however, because patients still must calculate their insulin dosage during meal times. But it did have benefits for reducing hypoglycemia overnight. This technology has opened doors for others to begin testing different approaches for creating a fully automated insulin delivery artificial pancreas system. While not a “cure” for type 1 diabetes, it could help improve management of the disease while decreasing the burden on patients.

There is still a great deal of research and work to be done before this type of treatment comes to fruition. And once it exists, there is no guarantee that every patient would choose to use it, just like not all patients choose to have continuous glucose monitors. But it would be another option that exists and could potentially have a significant impact on people’s lives.

The Diabetes Research Connection recognizes the life-changing impact that a T1D diagnosis has, and supports early career scientists in moving forward with novel research projects focused on preventing, curing, or managing type 1 diabetes. Through donations from individuals, corporations, and foundations, research funding is made possible. To learn more about current projects or make a donation, visit http://diabetesresearchconnection.org.

Learn More +

Could There be More than two Types of Diabetes?

and affects their body. Typically type 1 diabetes is diagnosed in childhood and type 2 diabetes develops later in life. However, a team of researchers in Europe and Asia may have identified another form of diabetes: maturity-onset diabetes of the young or MODY.

According to the researchers, MODY is believed to be “caused by a gene mutation and fueled by a lack of the insulin-stimulating hormone GIP.” Individuals with this condition have a mutation of the gene RFX6. Subjects of the study had typically developed MODY by the time they were 25, were not obese, were not insulin-dependent, and had an autosomal dominant inheritance of diabetes.

The researchers believe that the gene mutation results in the pancreas decreasing its insulin secretion, which is common in individuals with diabetes. However, subjects also had lower levels of the GIP hormone which stimulates and regulates insulin secretion. Researchers are hopeful that the creation of GIP analogs may help to treat MODY.

One challenge they have faced is distinguishing between individuals with type 1 or early-onset type 2 diabetes versus those who may have MODY. Improvements in gene testing and sequencing have allowed them to better identify RFX6 mutations.

As scientists and researchers develop a better understanding of diabetes, its forms, and how it impacts the body, it allows for more personalized treatment options. Individuals can find what works best for their specific type of diabetes and their body’s needs. The Diabetes Research Connection encourages and supports novel studies on type 1 diabetes to expand understanding and treatment approaches. Early career scientists receive up to $50,000 in funding for research projects. Learn more about current projects and how to support these efforts by visiting http://diabetesresearchconnection.org.

Learn More +

Could Blood Stem Cells Be Used to Reverse Type 1 Diabetes?

Researchers know that in individuals with type 1 diabetes, the body mistakenly attacks and destroys insulin-producing beta cells that are used to regulate blood sugar levels. One of the challenges in treating T1D is finding a way to stop this process, or safely introducing new cells to take their place but protecting them from the body’s autoimmune response. This has proven difficult.

Researchers at Boston Children’s Hospital may have found a way to overcome these challenges by combining the patient’s own blood cells with a healthy PD-L1 gene or a targeted molecule “cocktail” of interferon beta, interferon gamma, and polyinosinic-polycytidylic acid. Both of these approaches had the same effect.

Scientists found that the problem with current treatments involving immunotherapy or injecting patients with their own blood stem cells is that these cells are still defective in producing PD-L1, a protein that helps protect against T1D. By introducing a healthy PD-L1 gene (or the “cocktail”) in mice with diabetes, the disease was reversed. In nearly all of the mice, the diabetes was cured in the short term, and in one-third of the mice, these results were long-term. In addition, there were no adverse effects of the treatment.

The researchers are working on gaining approval for human trials to test this therapy, and partnering with Fate Therapeutics to create a pill that would introduce these healthier blood stem cells. More extensive testing is necessary to determine how long the treatment is effective and how frequently it would need to be re-administered. However, it is encouraging to see the initial reversal of T1D in mice and what that may mean in the future for humans with the disease.

The Diabetes Research Connection strives to help early career scientists continue advancing research and treatment options for type 1 diabetes. With the support of individuals, corporations, and foundations, novel research projects can receive up to $50,000 in funding. Learn more about current projects and how to support these efforts by visiting http://diabetesresearchconnection.org.

Learn More +

Potential Benefits of Incorporating Metformin in Type 1 Diabetes Treatment

Traditionally metformin is a drug used to help control blood sugar in individuals with type 2 diabetes. However, a recent study examined its effects in patients with type 1 diabetes. More specifically, the study looked at the impact on vascular health because individuals with T1D tend to be at higher risk of developing cardiovascular disease.

The researchers conducted a double-blind, randomized, placebo-controlled trial on 90 children in South Australia between the ages of 8 and 18 who had been diagnosed with T1D for at least six months. Half the of participants received metformin, and the other half received a placebo. A baseline vascular function was determined at the start of the trial and then tested at three, six, and 12 months. In addition, HbA1C, insulin dose, and BMI were also recorded at each visit. Throughout the trial, participants were asked about any side effects they may be experiencing so that therapy could be adjusted accordingly. Treatment compliance was also tracked.

The results showed that over the course of one year, vascular function improved in the metformin group compared to the control group. The difference was most noticeable at the three-month interval, and this is also when there was the greatest improvement in HbA1C levels for those in the metformin group. The difference was lower at the 12-month mark, but still significant. In addition, children in the metformin group also showed a decrease in the amount of insulin required over 12 months. Children with above-average BMIs who were taking metformin also showed improvement in vascular smooth muscle function. Overall, there were positive results for children with T1D taking metformin as compared to those receiving a placebo. However, the study was not continued long enough to determine potential changes in vascular structure, only vascular function.

With further testing, this could lead to more diverse treatment options for individuals with type 1 diabetes to help better control blood sugar and maintain a higher quality of life. It is these types of changes, as well as advancements in the treatment and prevention of T1D, that the Diabetes Research Connection aims to support. By funding novel research projects, the Diabetes Research Connection helps early career scientists to keep their work moving forward. Visit http://diabetesresearchconnection.org to learn more.

Learn More +

Treating Type 1 Diabetes with Synthetic Cells

Treating type 1 diabetes (T1D) takes careful planning and calculation. Individuals must test their blood to determine their blood glucose level, then calculate exactly how much insulin they need to inject. They must pay careful attention to what they eat and how their body responds. This is because, with type 1 diabetes, the body’s immune system mistakenly attacks and destroys insulin-producing beta cells. In individuals without T1D, these beta cells automatically secrete insulin to keep blood glucose levels in check.

However, researchers from the University of North Carolina and North Carolina State are testing synthetic cells that could replace those cells that have been destroyed and automatically release insulin in response to the body’s needs. They have created “artificial beta cells” or AβCs that are packed with insulin-stuffed vesicles. When blood sugar rises, the coating of the artificial cells changes and insulin is released. The cells would need to be injected every few days, or can be delivered by a skin patch that is replaced regularly.

These AβCs are an advancement in potential treatments for T1D. There are some studies regarding transplanting cells – whether donor cells, modified cells, or harvested cells – but the challenge is that they often require some immune suppression, can be very expensive, and the body generally ends up destroying these cells as well. The synthetic cells would be regularly replaced with new AβCs as they distributed their insulin. Studies conducted in mice have found that blood glucose levels returned to normal levels within one hour and were maintained for up to five days.

According to John Buse, MD, PhD, the Verne S. Caviness Distinguished Professor at UNC, chief of the division of endocrinology, and director of the UNC Diabetes Care Center who is a co-author of the study, “There is still much work needed to optimize this artificial-cell approach before human studies are attempted, but these results so far are a remarkable, creative first step to a new way to solve the diabetes problem using chemical engineering as opposed to mechanical pumps or living transplants.”

While this approach is still in development and requires more extensive testing, it is a step in the right direction for improving quality of life for individuals with T1D and improving management of the disease.

The Diabetes Research Connection supports innovative research to prevent or cure type 1 diabetes, reduce complications of the disease, and improve quality of life. Early career scientists can receive up to $50,000 in funding for their research through donations by individuals, corporations, and foundations. To learn more about current projects and support these efforts, visit http://diabetesresearchconnection.org.

Learn More +

Comparing Insulin Pumps and Injections for Managing Type 1 Diabetes

Learning how to effectively manage type 1 diabetes can take time. It takes practice and trial-and-error to understand how each person’s body responds to different foods, activities, and insulin doses. A recent study found that children with type 1 diabetes may be able to control blood sugar levels more effectively and reduce risk of complications by using insulin pumps as opposed to manually injecting insulin.

The study was conducted by the University of Metabolic Research Laboratories and analyzed data for 14,460 patients with insulin pumps and 16,460 who injected insulin. All participants had been diagnosed with type 1 diabetes for at least one year and were younger than 20 years old. The results for children and adolescents using pumps outperformed those who did not.

According the findings, only 9.55 children per 100 experienced severe hypoglycemia each year when using insulin pumps compared to 14 children per 100 for those who relied on injections. Along the same lines, 3.64 children per 100 were treated each year for diabetic ketoacidosis (DKA) while on an insulin pump compared to 4.26 children per 100 for those treated with injections. Furthermore, HbA1c levels and daily insulin doses were slightly lower for those with insulin pumps as well.

The results highlight the importance of considering insulin pumps for children living with type 1 diabetes and ensuring that they are educated on their condition and how to properly use the pump for blood sugar control. However, this is only one option available and may not be the best choice for all children. Dr. Simon Heller from the University of Sheffield was not involved in the study but notes, “For adolescents, particularly those who find it difficult to do all the complicated things in managing diabetes, pumps may not be the best option, particularly if insulin is missed.” Parents, children, and medical provider should work together to determine the best option for each individual.

The Diabetes Research Connection supports early career scientists in novel studies regarding type 1 diabetes in an effort to develop more effective treatment options, potential cures, and options for improving quality of life. For more information about current projects and opportunities for funding, visit http://diabetesresearchconnection.org.

Learn More +

New Biomarker May Help with T1D Detection, Prevention, and Treatment

As scientists continue studying type 1 diabetes (T1D), they develop a deeper understanding of changes that occur in the body. It has been known for a while that the body attacks insulin-producing beta cells in the pancreas leaving the body unable to regulate blood sugar. Researchers have recently discovered that MAIT cells within the body – cells that are activated by bacteria and associated with mucosae – may also play a role. They are part of the body’s innate immune system and may serve as a biomarker for early detection of T1D.

The study, which was conducted by AP-HP Necker-Enfants Malades Hospital in Paris and the Cochin Institute, examined blood sample from patients with and without T1D, as well as animal models. The results showed that MAIT cell levels were lower in the blood of children diagnosed with T1D than those who were not. This could be because the MAIT cells had migrated to the pancreas in children with T1D; they are believed to play a role in the destruction of insulin-producing beta cells. But one interesting point to note was that before T1D had even developed in the animal models, the MAIT cells were already altered. This could serve as an early form of detection and prevention of the disease.

The mutation in MAIT cells may also contribute to gut mucosa being more susceptible to bacteria. This may lead to an increased autoimmune response. When MAIT cells are functioning normally, they help maintain homeostasis in the gut mucosa.

Scientists may be able to use this information to enhance early detection of T1D, develop strategies for prevention, or improve targeted treatment options. More research is needed to explore the link between MAIT cells and gut microbiota, but this is a starting point.

The Diabetes Research Connection actively supports novel research regarding preventing, treating, and potentially curing T1D. The organization raises funds that are provided to early career scientists for innovative research projects. To learn more and support their efforts, visit http://diabetesresearchconnection.org.

Learn More +

A Multitude of Potential Treatment Options for Type 1 Diabetes

Type 1 diabetes is a condition that does not discriminate. It affects males and females of all races and ethnicities around the world. Researchers in many countries are striving to develop effective treatment options that help the body to regulate blood glucose on its own and reduce the need for constant monitoring and insulin injections. At the Kyoto Diabetes Mini-Symposium in June 2017, researchers presented various studies and their potential impacts. Here is an overview of some of the treatment options being explored:

Islet Transplantation: Islet transplantation is one option that scientists have been working on for many years. Patients receive infusions of human islet cells to replace the cells their bodies have mistakenly destroyed. Studies have shown that this approach has resulted in improved glycemic control and hypoglycemia awareness, as well as protection from severe hypoglycemic events in some patients. However, there are still challenges regarding the lifespan of the graphs and their prolonged effectiveness.

Cell Sourcing from Large Animals: One challenge that researchers have faced in islet transplantation is generating a sustainable amount of islet cells. Scientists have turned to large animals such as pigs to try to cultivate a new source. Studies have found that porcine islet cells function very similarly to human islet cells. However, there is concern over the potential transmission of porcine endogenous retroviruses, so scientists have been experimenting with gene editing to inactivate contributing sections of various genes and reduce risk.

Scientists are also exploring the possibility of generating a human pancreas inside a pig so that it will produce human islet cells. Similar studies have been done with rats and mice where each has developed a pancreas for the other. There are many ethical concerns and regulations to be considered with this approach, however.

Human Stem Cell-Derived Beta Cells: Scientists are exploring the potential of targeting human stem cells and guiding them into developing into pancreatic progenitor cells and eventually mature insulin-producing beta cells. Ideally, this would allow the body to better regulate its own blood glucose levels. Researchers are working on improving differentiation protocols and determining the best host conditions for the cells.

Cell Encapsulation: Current treatment involving transplantation requires patients to take medication that suppresses the immune system to keep it from attacking the transplanted cells or organs. While it protects the transplant, it puts patients at risk for a variety of complications. Scientists are working on a process to encapsulate islet cells in a device that protects them from an immune system attack. They are experimenting with different materials, locations, and processes to determine what may potentially work best.

These are just a few of the strategies scientists are investigating to help treat and potentially cure type 1 diabetes. There is still a lot more research and testing necessary to fully explore these options and their safety and efficacy. It is these types of innovative approaches that continue to advance knowledge and treatment regarding type 1 diabetes. The Diabetes Research Connection supports early career scientists in developing their research by providing essential funding. To learn more about current projects and contribute to these efforts, visit http://diabetesresearchconnection.org.

Learn More +

Gallbladder Cells May Be A Viable Source for Treating Type 1 Diabetes

One of the main focuses of many studies regarding type 1 diabetes is how to generate new cells or reprogram existing cells to function as insulin-producing beta cells. Scientists have been exploring islet transplantation, gene editing, and more. Now, scientists from Oregon Health and Science University led by Professor Markus Grompe and Dr. Feorillo Galivo are evaluating the potential that human gallbladder cells may hold.

In type 1 diabetes, the body mistakenly destroys insulin-producing cells leading to uncontrolled blood glucose levels. The scientists introduced four new genes into harvested gallbladder cells which reprogrammed the cells to act more like the insulin-producing beta cells that the body had destroyed. In laboratory testing, these cells were able to respond to increased blood glucose levels by producing insulin. They also transplanted the cells into mice, but more research is needed to determine whether they are able to effectively control blood glucose levels. One issue that was discovered is that the cells had a very short lifespan, only surviving about four weeks. Some cells were also overly active.

They are still in the earlier stages of research and more testing and adjustment is necessary, but preliminary results show that this technique may hold great potential. This is yet another treatment strategy to explore and see how it can be used to treat and potentially cure type 1 diabetes.

The Diabetes Research Connection supports novel research projects by early career scientists providing up to $50,000 in funding. Projects are all focused on preventing and curing type 1 diabetes or improving quality of life for those living with the disease. To become a donor and support these initiatives, visit http://diabetesresearchconnection.org.

Learn More +

Simpler Measuring Technique May Help Identify Partial Clinical Remission in Type 1 Diabetes

One of the major challenges of type 1 diabetes is effectively managing blood glucose levels. It is a careful balancing act and differs for every patient. With type 1 diabetes, the body’s immune system mistakenly attacks and destroys insulin-producing cells. This means that patients require regular insulin injections to compensate. However, this is not a perfect solution and patients may still experience complications or side effects and need to be carefully monitored.

Researchers found that after children are initially diagnosed with type 1 diabetes and begin treatment, some experience partial clinical remission (PCR), also known as a “honeymoon period.” During this period, the pancreas is still producing some insulin on its own, and this can temporarily restore blood glucose levels to near normal. This means that patients require fewer or lower doses of insulin. The honeymoon period may last from three months to one year.

But not all children experience this effect. Those who do not are at a higher risk of developing diabetes-related complications. This makes it even more important for physicians to determine whether or not children go into partial clinical remission so they can develop a more effective treatment plan moving forward.

Traditionally partial clinical remission is determined by calculating daily insulin doses and average blood glucose levels and then analyzing the correlation (known as IDAA1C). This can take some time, and when faced with tight time schedules, physicians may not use this method as often as recommended.

In light of this, UMass Medical School physician-scientist Benjamin Nwosu, MD, began studying the accuracy of a simpler method. This approach involves evaluating the total daily dose of insulin the child receives compared to their body weight. If they receive less than 0.3 units per kilogram of body weight per day, it indicates they are in partial clinical remission. There were no major differences in results between using this method and the more complex IDAA1C technique. It is a faster way for clinicians to determine the same results and is just as reliable.

According to Dr. Nwosu, “Encouraging clinicians to use the total daily dose of insulin guideline will improve monitoring of PCR and, therefore, ensure the prevention of early hyperglycemia in patients who exceed it for better long-term outcomes.”

It is encouraging to see an emphasis on early detection and more effective treatment for type 1 diabetes. The Diabetes Research Connection raises funds for early career scientists who are pursuing novel research projects related to the prevention and cure of type 1 diabetes as well as improving quality of life for those living with the disease. One hundred percent of research funds go directly to scientists. To learn more and support innovative studies, visit http://drcnew.awp.uxtesting.net.

Learn More +

What Gene Editing Could Mean for Type 1 Diabetes

Altering human genetics is a sensitive subject. There are a lot of things that could potentially go wrong, but also many that could go right. CRISPR/Cas9 technology allows scientists to precisely cut out a segment of DNA and replace it with a new segment. By modifying specific genes, they could essentially eliminate certain diseases and remove inherited diseases from the human germline.

This unleashes new opportunities when it comes to treating – and potentially curing – diabetes. Scientists recently implanted skin grafts with a gene (GLP1) to stimulate insulin secretion by the pancreas. They attached these grafts to mice and found that the new genes helped to remove excess glucose from the bloodstream. Using skin grafts is a safe and relatively inexpensive process.

Researchers in Sweden managed to use CRISPR/Cas9 to switch off an enzyme that is involved in regulating the TXNIP gene which affects beta cell death and decreases insulin production. In Australia, the technology was used to try to identify rogue immune cells that attack the pancreas and contribute to the development of type 1 diabetes.

However, there is still more research that needs to be done to fully understand the impact of gene editing and potential effects that it could have. Though highly precise, there is still around a one percent chance of off-target effects occurring. These are changes to other parts of the genome outside of the area targeted by CRISPR/Cas9. There is a lot of risks involved with changing human DNA and many questions that are still unanswered. Furthermore, many of these studies have been conducted on mice and results do not always correlate exactly to humans.

But with more extensive testing and research, scientists may be able to find a safe way to treat or even cure diabetes through gene editing. Studies that exist so far hold potentially promising results. It is these types of cutting-edge, innovative approaches that could change the future of type 1 diabetes. The Diabetes Research Connection proudly supports early career scientists in pursuing novel research for type 1 diabetes. Learn more about current projects and how you can support these efforts by visiting http://diabetesresearchconnection.org.

Learn More +
Stem Cell

Tackling Type 1 Diabetes at a Cellular Level

In individuals with type 1 diabetes, the body mistakenly attacks insulin-producing cells and destroys them. This leaves the body unable to regulate the amount of sugar in the blood or shift the sugar into cells that convert it into energy. Uncontrolled blood sugar can take a toll on the body damaging the kidneys and heart and leading to other complications. Individuals with type 1 diabetes must take care to monitor their own blood sugar and administer the correct amount of insulin to make up for the work that would normally be done by the pancreatic cells.

However, researchers at the University of Pittsburgh are looking for a way to overcome these challenges by focusing on change at a cellular level. Since the body destroys insulin-producing cells, they are striving to replace them. The researchers want to use the body’s own pluripotent stem cells and turn them into pancreatic islet cells.

To do this, they must determine exactly how to manipulate the cells to get them to transform into the islet cells needed by the body. They are working in collaboration with other universities to further their studies.

According to Ipsita Banerjee, principal investigator in the study and a professor of chemical and bioengineering at the University of Pittsburgh, “We should be able to mass produce these islets, and actually, we have another grant where we are primarily looking into how to mass produce pluripotent stem cells.”

Results from early clinical trials show short-term improvement in more than half of participants. They were able to go off of insulin for two-week periods of time during the first year but most eventually had to continue using insulin injections. Further testing and clinical trials could help to improve these results.

This is far from the only study being conducted to improve the lives of individuals with type 1 diabetes. Researchers are continually striving to make innovate breakthroughs and try cutting-edge approaches. The Diabetes Research Connection supports early career scientists with up to $50,000 in funding for research on type 1 diabetes. These are projects that hold potential but may be passed over by more prominent and competitive funding sources. Learn more about the amazing work of these researchers and support their studies by visiting  http://diabetesresearchconnection.org. Every penny counts.

Learn More +

Could Beta Cell Age and Differentiation Play a Role in the Development of Diabetes?

The exact cause of type 1 diabetes is yet unknown. Researchers have a good understanding of how type 1 diabetes works and impacts the body, but not of the cellular intricacies that contribute to the development of the disease. A recent study examined the age and role of beta cells within pancreatic islets to better understand proliferation and function within the organ.

The study examined zebrafish and found that younger beta cells replicate more quickly than older beta cells, but they are less functional in terms of glucose responsiveness. As cells mature, they synchronize their proliferation and function.  In addition, within the pancreas differentiated cells are responsible for both organ growth and function, but it is yet undetermined whether certain cells make specific contributions to one factor or the other.  Organs such as the brain operate differently when it comes to increases in cellular mass and differentiation of cell function.

Through closer examination, researchers found that in the pancreas, beta cells differentiate according to the location in different parts of the embryo. In post-embryonic stages of development, beta cells from these different lineages are all brought together. This may also impact glucose responsiveness and the ability to balance insulin production with the energy necessary to support cell division. More research is necessary to determine exactly how proliferation and function affect heterogeneity in human beta cells and pancreatic islets.

The Diabetes Research Connection supports innovative and cutting-edge research when it comes to type 1 diabetes. Funds are raised for early career scientists to advance their research and contribute to the prevention or cure of type 1 diabetes as well as improving quality of life for those living with the disease. To learn more and support research efforts, visit http://diabetesresearchconnection.org.

Learn More +
Islet transplantation requires immunosuppressive drugs be taken for the rest of a person's life, though improving the body's ability to manage glucose levels significantly lowers the risk for adverse health events. islet transportation Andrey_Popov/Shutterstock

Researchers Target Immune System for Potential Type 1 Diabetes Treatment

The immune system plays an important role in type 1 diabetes; after all, it is the immune system that destroys insulin-producing cells. When cells are damaged or destroyed, it decreases the body’s ability to convert sugar to energy and produce insulin. Instead, individuals must monitor and adjust their insulin on their own through injections or an insulin pump.

In a small study, researchers examined the possibility of retraining the body’s immune system to not attack insulin-producing cells. They did this through the use of peptide immunotherapy. According to Simi Ahmed, senior scientist at JDRF, “The immunotherapy re-educates the immune system and teaches the cells that they shouldn’t attack the beta cells.”

This is done by injecting disease-related antigens to stimulate regulatory T-cells development and/or make them work better.  However, scientists have not yet determined exactly which antigens are responsible for type 1 diabetes. This is an area where more research is needed.

The study divided up 27 participants into three groups.  All participants had been diagnosed with type 1 diabetes within 100 days, because scientists wanted to test the immunotherapy before all or most of the T-cells had been destroyed, which is common in individuals who have had diabetes for many years.

One group received a placebo drug, one group received immunotherapy every four weeks, and one group received immunotherapy every two weeks. The results showed that the control group had decreased C-peptide levels at 3, 6, 9, and 12 months, but those who received immunotherapy every four weeks had no decline in C-peptide levels. The group that received immunotherapy every two weeks showed a decline in C-peptide levels at 12 months.  When C-peptide levels decrease, it means that less insulin is being produced.

While the test group was too small to determine why these variations occurred, it does show that there is potential in this therapy and more extensive testing is needed with a larger group.  There were no noted side effects, meaning immunotherapy appears to be safe for individuals with type 1 diabetes.

Further research is needed to determine how often immunotherapy would be needed and whether individuals who have had the disease for many years could potentially benefit. Studies have shown that some people who have had diabetes long-term still have detectable C-peptide levels.

This study opens the door for many new trials and areas of research. Immunotherapy is an approach that may hold great potential upon initial diagnosis of type 1 diabetes. The Diabetes Research Connection supports this type of innovative research and funds studies that are often deemed high-risk. Learn more about the projects backed by the Diabetes Research Connection by visiting us online and consider donating to the cause.

Learn More +

Exploring the Impact of Gut Bacteria on Type 1 Diabetes Risk

Over the years, researchers have significantly improved their understanding of type 1 diabetes, but there are still many questions left unanswered. They still do not understand exactly why some people develop this condition and others do not, and there is still no cure.

A recent study is taking a closer look at the role gut bacteria plays as a risk or protective factor in the development of type 1 diabetes.  Scientists at Harvard Medical School studied mice who were bred to develop diabetes and altered their genetics and levels of gut bacteria.  Each mouse carried a gene variant that was shown in other studies to protect against diabetes.  During the first six weeks of their lives, the mice were given antibiotics, and the scientists believe that this disrupted the natural balance of gut bacteria reducing their protection against diabetes.  The mice showed inflammation of the pancreas, which often precedes type 1 diabetes.

However, they also found that those mice who inherited the protective gene from the mother were still resistant to diabetes, but those that received it from the father were not. This could be an important link between the protective abilities of gut microbiota and genetics passed between mother and baby.  But it is important to note that there are “significant physiological differences” between mice and humans according to Diane Mathis, lead author of the study and professor in the Department of Microbiology and Immunology at Harvard Medical School.

Though more extensive research needs to be conducted, especially to determine how the results may correlate to humans, scientists believe that reducing exposure to antibiotics in newborns and pregnant women may be beneficial in reducing risk of type 1 diabetes or maintaining gene protection.

These types of studies are essential in advancing research to prevent and cure type 1 diabetes. The Diabetes Research Connection strives to provide early career scientists with the funding necessary to pursue innovative research for type 1 diabetes.   One hundred percent of research funds raised go directly to the scientists. To learn more about current projects or make a donation, visit http://drcnew.awp.uxtesting.net.

 

Learn More +

Younger Scientists Gain More Support for Research Grants

 

The National Institutes of Health (NIH) is incredibly well-known for its grant offerings to support innovative research. Over the years, it has funded millions of dollars’ worth of research initiatives. However, a recent finding by a professor of structural biology and an informatics researcher has uncovered a disturbing trend – many of the grants awarded by the NIH go to older principal investigators (PIs), and younger scientists are missing out.

According to their study, since 1982, PIs under age 46 have received fewer grants than older PIs. Many of the grants have been awarded to PIs over age 55. While there are committees in place that review proposals and determine who receives the grants, these committees are made up of grantees – many of whom happen to be older, since that has been the trend in awards. The study suggests that these committees may be more hesitant to award grants to younger PIs because they are young and have less experience.

However, the NIH is taking steps to change its processes and shift more grant awards toward younger PIs. They plan to put a cap on how many grants PIs can have at one time and already implemented a policy that examines age bias in awarding grants.

“This is why the Diabetes Research Connection (DRC) is an important source of funding for innovative research that, because of ‘its high-risk,’ is almost impossible to fund from traditional funding sources,” says President and Co-Founder Alberto Hayek, M.D.

Supporting early career scientists is one of the reasons the Diabetes Research Connection was initially founded. The organization focuses on connecting these researchers with funding to advance their studies and explore topics that may be considered too high-risk by other institutions. Through the DRC, scientists can receive up to $50,000 for research projects focused on preventing or curing type 1 diabetes, minimizing its complications, or improving quality of life for those living with type 1 diabetes.  One hundred percent of donations for research go directly to the scientists. To learn more about the Diabetes Research Connection and find out how you can support innovative research, visit http://diabetesresearchconnection.org.

Learn More +

Is the Secret to Stopping Type 1 Diabetes in Your Gut?

Type 1 diabetes can be a challenging condition to manage. Because the body destroys insulin-producing beta cells, patients require regular blood glucose monitoring and use of insulin injections to stabilize their blood sugar levels. This differs from type 2 diabetes, which can in some cases be managed through targeted diet and exercise plans.

Changes in diet and lifestyle were previously thought to have little influence on type 1 diabetes because of the nature of the disease. It is not just that the body is not creating enough insulin, it is the fact that the body attacks and destroys the very cells that produce it.

However, new research is changing scientists’ understanding of type 1 diabetes and potential treatments. They have found that metabolites in the gut may help protect against type 1 diabetes. That means that changing one’s diet may make a difference. More specifically, adding whole foods that are high in fiber.

Researchers have been studying the effects of acetylated or butyrylated high-amylose maize starch on mice. Acetate and butyrate are short-chain fatty acids (SCFAs) that not only affect metabolism of glucose and cholesterol, but are also used for energy, immune tolerance to food antigens, increasing gut barrier function, and reducing inflammation. When mice were given acetate-infused water for five weeks, their incidence of type 1 diabetes was 30 percent lower than the control group – 40 percent versus 70 percent. After 10 weeks, the amount of immune cells that had infiltrated the pancreatic cells had decreased as well. The acetate water combined with acetylated or butyrylated high-amylose maize starch stopped the progression of type 1 diabetes in the mice.

SCFA supplementation is already being studied in clinical trials for gastrointestinal disorders and has shown positive results and no negative effects. Research will now expand to include SCFA supplementation for treatment of type 1 diabetes.

While typical foods do not contain acetylated or butyrylated high-amylose maize starch, they do contain regular maize starch, and that has been found to be effective as well.  Eating a diet rich in high-fiber foods can stimulate the production of acetate and butyrate in the colon, thus potential supporting gut health and reduced risk of type 1 diabetes.

Beneficial foods include garlic, onions, leeks, asparagus, artichokes, beans, legumes, potatoes, rice, apples, oranges, bananas, cherries, and apricots. Just be sure to slowly introduce more fiber into the diet to allow the body time to adjust and reduce uncomfortable side effects such as stomach cramps or gas.

Using food for medicinal purposes is nothing new – it has been done for centuries. However, it is something that is often overlooked. These recent studies open doors to potential treatments and prevention methods for type 1 diabetes but require further research and testing. Organizations such as the Diabetes Research Connection support early career scientists in pursuing this type of work and advancing understanding and treatment of type 1 diabetes. Learn more and find out how you can support various projects at http://diabetesresearchconnection.org.

Learn More +

Cell Encapsulation Shows Potential for Treating Type 1 Diabetes

One of the challenges of treating type 1 diabetes is developing a process that will stimulate insulin production without triggering the body’s immune system to attack these cells. Many potential solutions have undesirable side effects, only short-term success, or still require immune system suppression, which can be hard on the body.

Current studies have been focused on the use of islet transplantation to help manage blood glucose levels. Researchers have been trying to determine the most effective location for islet transplantation, and how to reduce rejection and providing lasting results.  One approach that has shown great potential is using macro- or microencapsulation of islet cells. This provides a layer of protection for the cells while still allowing the exchange of oxygen, nutrients, glucose, and insulin. Scientists must determine the optimal thickness and composition of the encapsulation device to allow the cells to remain viable, protected from immune response, and effective at moderating blood glucose levels. Some mice have shown a positive response to use of macroencapsulation devices and human stem-cell-derived insulin-producing cells for managing diabetes.

This study has only been conducted using animals so far, therefore more research and testing is needed before it is approved for human trials or treatment. Cell replacement therapy has come a long way and appears to be an effective path toward treating and potentially curing type 1 diabetes in the future. The use of human stem-cell-derived insulin-producing cells may help overcome shortages of islet donations and allow more patients to receive cell replacement therapy for type 1 diabetes. You can learn more about this study here.

The Diabetes Research Connection supports ground-breaking research studies that show potential in improving treatment and prevention of type 1 diabetes. All funding goes directly to early-career scientists’ research projects allowing them to advance their investigations. Help support the future of diabetes research and the effort to find a cure by donating today.

Learn More +
Laboratory Equipment - microscope

Support by DRC Enabled an Early-Career Scientist to Contribute to a Major Study Published in “Cell Report”

Support by DRC enabled Wendy Yang, Ph.D., to contribute to a major study published in Cell Report. In this study, the investigators discovered that alpha-catenin, a protein that regulates cell-cell interactions and communication is a potent regulator of pancreatic islet cell development. Click here to read the full article.

Learn More +

DRC Funding Precipitates $1M Grant

Securing adequate funding is imperative for scientists to explore novel ideas and advance their research. Unfortunately, federal funding can be incredibly competitive, and organizations are not always willing to take chances on high-risk projects. This makes other funding sources – such as the Diabetes Research Connection – all the more important. And one person who knows this well is Duc Dong, Ph.D.

Dr. Dong is an assistant professor in the Human Genetics Program at Sanford Burnham Prebys Medical Discovery Institute, and a recent recipient of a $1M grant from the W.M. Keck Foundation.  This grant will be used to further his research into reprogramming some of the body’s own cells to take on new functions, such as converting skin cells into cells that would ultimately be able to produce insulin. Dr. Dong is developing a process to do this without removing the cells from the body or transplanting manipulated cells. This has the potential to be a huge step forward in treating and potentially curing type 1 diabetes.

However, prior to being awarded the W.M. Keck Foundation grant, one of Dr. Dong’s investigators in his lab, Joseph Lancman, Ph.D., received nearly $47,000 in funding through the Diabetes Research Connection. This allowed Dr. Dong’s lab to move forward with his research on reprogramming cells and build a stronger foundation to support the work that he will do with the Keck Foundation grant.

“The Diabetes Research Connection, like the Keck Foundation, plays a critical role in biomedical science by supporting innovative projects that most other funding sources consider high-risk,” says Dr. Dong. “However, these high-risk projects have high-reward potential, essential for stemming next generation technologies. My vision is to advance in-vivo lineage conversion technology to make it a practical new approach for regenerative medicine.”

The Diabetes Research Connection celebrates Dr. Dong’s continued success and is excited to see how this grant will help him to further develop his ideas and take them to the next level. The organization is proud to have been able to support him in the earlier stages of his work and is committed to providing critical funding to innovative research projects regarding type 1 diabetes. To learn more or contribute to current projects, visit DiabetesResearchConnection.org.

Learn More +

Examining Potential Complications for Type 1 Diabetes

Effective management of blood glucose levels is essential for people with type 1 diabetes. Should blood sugar become too high or too low, it can have dangerous results. Every person’s situation is different.  Some people can use oral agents to control their diabetes, some use injections, and still others have insulin pumps. It is all about figuring out what works best for each individual.

A recent case study examined a 36-year-old gentleman who was diagnosed with type 1 diabetes 15 years ago. One of the challenges that he faces is that he is homeless and does not always have the necessary supplies to manage his diabetes. He was brought to the emergency room with hyperglycemia and possibly diabetic ketoacidosis.  He received daily insulin but did not take meal doses of fast-acting insulin (insulin aspart), only corrective doses to treat hyperglycemia.

The emergency room determined that he did not have diabetic ketoacidosis, which occurs when the body does not have enough insulin and starts breaking down fats and muscle for energy which releases ketones into the blood causing a chemical imbalance.  He was provided with a correct dosage of insulin to correct the hyperglycemia and prescribed three meals per day.  Since this was challenging given that he was homeless, a social worker helped him to make arrangements to stay with family and get medical assistance to afford supplies to manage his diabetes.

The medical staff was tasked with accurately determining the proper dose of insulin to treat the hyperglycemia as well as what his daily insulin needs were.  Basal insulin doses are about half of the daily requirement, and the rest is accounted for by bolus injections. Blood work was completed to determine whether or not he had diabetic ketoacidosis.

These are issues that people with type 1 diabetes must always be alert for. Understanding potential complications, how to identify warning signs, and how to treat these conditions is imperative. Researchers are always studying ways to better prevent, diagnose, treat, and cure type 1 diabetes. The Diabetes Research Connection supports early career scientists through funding for their research projects. To learn more, visit http://diabetesresearchconnection.org.

Learn More +

Could a New Pill Simulate the Effects of Exercise in People with Diabetes?

Staying physically active is essential for good health, especially for those with diabetes. Exercise increases insulin sensitivity and can improve heart health. However, those with diabetes must carefully monitor their body’s response to exercise and how it affects their blood sugar. Sometimes maintaining regular physical activity can be difficult – even more so if there are other co-existing health problems.

But a new pill may change all that by enabling people with diabetes to experience the effects of exercise without the physical exertion. The drug works by activating a gene pathway normally stimulated by running resulting in improved stamina and endurance as well as increased fat burning. This is encouraging for those with diabetes because the body typically burns sugar (glucose) before fat because fat-burning takes longer. This new drug activates fat burning and allows sugar to be used to support brain function.

The gene central to the study is PPAR delta, or PPARD. When mice were given the drug for eight weeks to continually activate PPARD, they experienced less weight gain, improved blood sugar control, and increased endurance. Their insulin responsiveness was on par with that of long-distance runners.  Mice given the drug were able to run on a treadmill for 270 minutes before becoming exhausted, compared to just 160 minutes for those mice not given the drug.

According to Weiwei Fan, first author of the research paper and a research associate at the Salk Institute where the study is being carried out, “Exercise actives PPARD, but we’re showing that you can do the same thing without mechanical training. It means you can improve endurance to the equivalent level as someone in training, without all of the physical effort.”

This drug could open the door to new treatment options for people with diabetes by triggering fat burning and supporting improved insulin sensitivity. Currently the only study trials have been on mice, but there is interest in developing clinical trials for humans. Scientists are continuing to study potential therapeutic applications and the effect they have on health.

The Diabetes Research Connection is committed to supporting these types of innovative research efforts by raising funds for early career scientists studying type 1 diabetes. Research funding is essential for leading the way to breakthroughs in treatment, prevention, and potential cures for diabetes. To learn more about how the Diabetes Research Connection is making a difference, visit us online.

Learn More +

Technology of the Future: Using Smartphones to Manage Diabetes

Technology has made leaps and bounds over the years, impacting practically every facet of our lives. Previous limitations are constantly being tested and pushed, and healthcare is no exception. While blood glucose monitoring devices and insulin pumps already exist, technology is taking these processes a step further.

A research team led by Jiawei Shao has leveraged smartphone technology combined with far-red light to test a potential new treatment for diabetes. One of the major challenges people with diabetes struggle with is maintaining stable blood sugar. This often involves constant blood testing and adjusting insulin dosages. The researchers may have found a way to make these processes more precise and automatic. They designed custom cells that respond to far-red light by producing insulin.

The cells were combined with wirelessly-powered red LED lights in a bio-compatible sheath that can be implanted into the skin. The technology is controlled wirelessly by a smartphone application. The application can activate the red LED lights to trigger insulin production in response to blood sugar readings provided by a Bluetooth-enabled blood glucose meter paired with the application.

This study is in the very early stages, having only been tested in a small pilot study using mice. However, the researchers explained that “successfully linking digital signals with engineered cells represents an important step toward translating similar cell-based therapies into the clinic.” With millions of people struggling to effectively manage their diabetes, this could become a potentially life-changing treatment option. There is clearly much more research and testing that needs to be conducted before it would reach human trials or approval, but it demonstrates the incredible potential of advanced technology and synthetic biology in future healthcare.

The Diabetes Research Connection proudly supports early career scientists and researchers by funding emerging research aimed at the prevention, diagnosis, treatment, and cure of type 1 diabetes. Learn more about the amazing work of these individuals and teams and support their projects at http://drcnew.awp.uxtesting.net/.

Learn More +

Could Bacteria in the Body Lead to a Cure for Type 1 Diabetes?

For decades, researchers have been searching for a cure for type 1 diabetes. They have refined their understanding of its cause and continue to learn more each day. One would think that this would make finding a cure easier, but it’s not that simple. While scientists have developed complex solutions that mimic the body’s ability to produce insulin on its own, these methods are always undermined by the fact that the body’s immune system continues to destroy insulin-producing cells. And often treatment still requires a great deal of input and involvement from patients.

However, John Glass, a synthetic biologist at the J. Craig Venter Institute who is living with type 1 diabetes himself, may have found a promising new idea for a cure – or at least another step in the right direction. By using synthetic biology, he believes he may be able to re-engineering bacteria found deep within the skin to perform similar functions of beta cells, which are involved in the natural production of insulin. The idea stems from a study that re-engineered embryonic kidney cells to mimic pancreatic functions and create a closed loop system where the body could stabilize its own blood sugar and insulin production. This ended up only being a temporary fix because the body still targeted and destroyed these cells much like naturally occurring beta cells.

Glass’ research builds on this concept, but takes a different approach by using bacteria living deep within the skin that the immune system already overlooks. These bacteria were first discovered by Richard Gallo, a dermatologist at the University of California-San Diego (UCSD).  Alberto Hayek, a diabetes researcher and emeritus professor at UCSD, approached Glass about re-engineering these microbes to function like beta cells but still go undetected by the immune system.

The study is in very early stages, but the idea is to harvest a patient’s own bacteria, re-engineer the microbes, and then apply them transdermally through a personalized skin cream. They would be absorbed into the skin and start functioning as beta cells. There are still many obstacles to overcome with this approach, however. For instance, researchers would need to determine how many microbes need to be used and how to regulate the bacteria from producing too much insulin. There is also the risk of the body attacking the modified insulin, and the fact that bacteria are not the best at building structures that make up insulin.

But it is a starting point, and one that in theory could hold a great deal of promise. It will likely be years before this research would begin yielding further testing or results, but the process is starting as Glass further develops his study and seeks funding to start experimentation using mice.

It is these types of ideas and experiments that keep type 1 diabetes research moving forward, but support and funding are critical. The Diabetes Research Connection aims to help early career researchers overcome some of these challenges by providing funding for research into prevention, treatment, and cures for type 1 diabetes. To learn more about current projects and support these efforts, visit www.diabetesresearchconnection.org.  

Learn More +

Medication Approved to Treat All Forms of Diabetic Retinopathy

One of the risks associated with diabetes is diabetic retinopathy. This condition affects approximately 7.7 million Americans and is the leading cause of blindness in adults with diabetes between the ages of 20 and 74. Diabetic retinopathy occurs when high blood sugar damages blood vessels in the retina. It can impact individuals in a variety of ways, from blood vessels swelling and leaking to closing off completely to abnormal blood vessel growth. All of these situations can adversely impact vision and have the potential to cause blindness.

When the blood vessels leak causing the macula to swell, this is known as diabetic macular edema or DME. In October 2016, Genentech, a subsidiary of Roche, received FDA approval for the drug Lucentis as a treatment for diabetic retinopathy with DME.  This drug is an anti-vascular endothelial growth factor agent. Two studies were conducted on 759 patients and found positive results in reducing vision impairment.

Due to this success, Roche applied to have the drug approved in patients with diabetic retinopathy without DME. The studies showed that 38 percent of patients without DME experienced at least a two-step improvement in their diabetic retinopathy, and 28 percent experienced at least a three-step improvement. Since diabetic retinopathy is considered an area of high unmet need, the FDA granted priority review of Lucentis. In turn, Lucentis was approved as the only FDA-approved medication for the treatment of all types of diabetic retinopathy in patients both with and without DME in February 2017.

With more than 29 million Americans living with diabetes, this breakthrough has the potential to make a positive impact on visual health. Uncontrolled or poorly controlled diabetes puts individuals at greater risk for diabetic retinopathy and vision loss. This medication may help improve vision loss and protect eye health. The Diabetes Research Connection looks forward to learning more about the efficacy of this medication and its potential to lead the way to more treatment options. Every day researchers are striving to learn more about type 1 diabetes and develop better ways of preventing, diagnosing, treating, and potentially curing this condition. The Diabetes Research Connection provides necessary funding to support early-career scientists in their research. To learn more and support these studies, visit the Diabetes Research Connection website.

Learn More +

Incidence of Type 1 Diabetes Increase Among Youth

Diabetes affects an estimated 29.1 million Americans, including around 208,000 youth under age 20. This includes both diagnosed and undiagnosed type 1 and type 2 diabetes. And unfortunately, these rates appear to be on the rise according to a new study funded by the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH).

Between 2002 and 2012, the number of youth (ages 0 to 19) newly diagnosed with type 1 diabetes increased by around 1.8 percent per year. For type 2 diabetes, this incidence was even higher with an increase of approximately 4.8 percent per year. The study went even further to break down data by five major racial/ethnic groups including non-Hispanic whites, non-Hispanic blacks, Hispanics, Asian Americans/Pacific Islanders, and Native Americans. The study, known as the SEARCH for Diabetes in Youth study, included 11,244 youth ages 0 to 19 with type 1 diabetes and 2,846 youth ages 10 to 19 with type 2 diabetes.

The study found that for type 1 diabetes, there was a greater increase in diagnoses among Hispanic youth (4.2 percent) than other groups.  The rate for non-Hispanic blacks was 2.2 percent, and non-Hispanic whites was 1.2 percent.  However, when it came to type 2 diabetes, the greatest increase was seen among Native American youth with a rate of 8.9 percent. (Note: The rate for Native Americans cannot be generalized for all Native American youth nationwide because participation in the study was not representative of all Native American youth in the United States.)

There was also a contrast when it came to gender. While males saw a greater increase in new diagnoses for type 1 diabetes (2.2 percent) versus females (1.4 percent), when it came to type 2 diabetes, females had a higher incidence of diagnoses (6.2 percent) compared to males (3.7 percent).

According to Barbara Linder, M.D., senior advisor for childhood diabetes research at NIH’s National Institute of Diabetes and Digestive and Kidney Diseases, “These findings lead to many more questions. The differences among racial and ethnic groups and between genders raise many questions. We need to understand why the increase in rates of diabetes development varies so greatly and is so concentrated in specific racial and ethnic groups.”

This study may lead the way to new research opportunities for scientists as they seek to better understand diabetes and more effective ways to diagnose, treat, prevent, and cure this disease. The Diabetes Research Connection supports these efforts by raising funds for emerging scientists who are studying type 1 diabetes. To learn more about current projects and support these efforts, visit http://diabetesresearchconnection.org.

Learn More +

Are Contact Lenses the Next Breakthrough in Blood Glucose Monitoring?

If you have diabetes or know someone who does, you know that monitoring blood glucose levels is essential to good health. Through these readings, individuals can track whether their blood sugar is too high, too low, or just right. However, current methods include finger pricks to test blood or the insertion of tiny electrodes under the skin for continuous monitoring. Both methods have their pros and cons.

Dr. Gregory S. Herman, a chemical engineering professor at Oregon State University, and two of his colleagues are striving to change this process. They have been leveraging the power of chemistry and technology to develop contact lenses with transparent sensors that would deliver critical health information such as blood glucose levels. These bio-sensing contact lenses could be replaced daily and are non-invasive.

So how would they work? Dr. Herman and his team created a biosensor “containing a transparent sheet of IGZO [indium gallium zinc oxide] field-effect transistors and glucose oxidase, an enzyme that breaks down glucose.” As glucose was added, it was oxidized and changed the pH level of the mixture, which was detected by the current in the IGZO transistor. Because the concentration of glucose in the eye is very low, they had to create a sensor that was extremely sensitive and could detect glucose at a much lower concentration level than traditional biosensors.

According to Herman, “In theory, more than 2,000 transparent biosensors – each measuring different bodily function – could be embedded in a 1-millimeter square patch of an IGZO contact lens. Once developed, the biosensors could transmit vital health information to smartphones and other Wi-Fi or Bluetooth-enabled devices.”

This could change the way individuals with diabetes manage their health moving forward. Though the prototype could be a year or more away from beginning testing in animals, they are continuing to research and make progress on this initiative. They have received funding from the Juvenile Diabetes Research Foundation and the Northwest Nanotechnology Infrastructure.

Though not involved with this specific project, the Diabetes Research Connection also supports this type of research and innovation to make positive changes in the lives of those living with type 1 diabetes. The organization raises funds to support researchers in studies and projects to raise awareness, improve diagnosis and treatment, and search for cures for type 1 diabetes. To learn more, visit http://drcnew.awp.uxtesting.net.

Learn More +

Researchers Explore Link Between Gut Bacteria and Type 1 Diabetes

The number of people diagnosed with type 1 diabetes (T1D) continues to increase. Researchers estimate that by 2050, this number may reach 5 million. Ongoing efforts to prevent, treat, and cure type 1 diabetes aim to reduce the impact. One area that researchers are delving into is the study of gut bacteria.

When an individual has T1D, their white blood cells destroy insulin-producing beta cells that regulate blood sugar. Scientists have discovered that gut bacteria share similar molecular markers with these beta cells. These similarities may stimulate more attacks on insulin-producing beta cells thereby increasing risk of T1D.

Ningwen Tai, Ph.D., associate research scientist at Yale Diabetes Center, has teamed up with other scientists to study this occurrence more closely. The researchers are particularly interested in Fusobacteria, which they believe appear in greater quantities in individuals prone to developing T1D. Their study began by examining the presence of Fusobacteria in mice and monitoring levels as diabetes risk increased.

Now they want to roll out this study to humans and explore whether tracking the level of Fusobacteria can predict the onset of diabetes. The study will analyze oral and fecal samples from individuals with T1D, as well as those at high risk and healthy individuals. These samples will be collected and studied over the course of a year or more.

If the Fusobacteria does accurately predict development of T1D, this could lead to targeted approaches for treatment and prevention. This would impact not only those with T1D, but also individuals who are at risk for developing the disease. Doctors would be able to monitor the progression and take steps to counteract the impact of the gut bacteria.

The Diabetes Research Foundation is proud to support this research initiative by helping Dr. Tai and his team to raise necessary funds. It is through ongoing research that scientists advance their understanding of T1D and can be more aggressive regarding diagnosis, treatment, and prevention efforts. Click here to support Dr. Tai’s study on gut bacteria.

Learn More +

Medicare to Reimburse for Dexcom G5 Mobile CGM for Type 1 and Type 2 Diabetes

Frequent blood glucose testing can be expensive, especially for individuals who must intensively manage their insulin and adjust dosages. The cost of supplies can add up, but they are a necessity for good health. Some individuals may soon see some relief as Medicare recently agreed to cover therapeutic continuous glucose monitoring (CGM) systems and provide reimbursement. The Dexcom G5 Mobile CGM is currently the only system approved by the FDA for making treatment decisions that falls under this coverage.

Reimbursement would be available for individuals on intensive insulin therapy (either through multiple daily injections or a CSII pump) with Type 1 or Type 2 diabetes. Given current estimates of the number of intensive insulin users receiving Medicare, this could mean that more than 1 million people could be eligible for CGM coverage.  Reimbursement would include not only the G5 receiver, but also sensors, transmitters, and BGM and related supplies.

Dexcom CEO Kevin Sayer explains, “This is a new era and a huge win for people with diabetes on Medicare who can benefit from therapeutic CGM. This decision supports the emerging consensus that CGM is the standard of care for any patient on intensive insulin therapy, regardless of age.”

The broad scope of coverage criteria could mean that even more individuals may be eligible for coverage than previously thought. According to Dexcom, criteria includes:

  • Have diabetes;
  • Have been using a home BGM and performing at least four checks per day;
  • Are insulin-treated with MDI or a pump; and
  • Have an insulin treatment regimen that requires frequent adjustment on the basis of therapeutic CGM testing results.

The Dexcom G5 Mobile is categorized as “Durable Medical Equipment” under Medicare Part B, and qualifies as therapeutic CGM because it can be used to make treatment decisions. In addition, the system’s non-adjunctive label claim was approved in December. The ruling regarding coverage moved forward very quickly, and is a step forward for individuals living with diabetes.

There are currently other CGM systems on the market, but they have not yet been approved by the FDA as therapeutic CGM, therefore are not subject to coverage at this time.

The Diabetes Research Connection is excited to see how this will impact patients with diabetes moving forward. The organization strives to enhance research into the prevention, treatment, and cure of Type 1 diabetes through donor-driven funding. To learn more and support emerging research, visit www.diabetesresearchconnection.org.

Learn More +

New Drug May Help Slow Progression of Type 1 Diabetes

A major challenge with type 1 diabetes is that not only does the body lose its ability to produce insulin, the immune system also produces antibodies against the proteins in these insulin-producing beta cells. However, researchers at Linköping University in Sweden have made an exciting discovery that may prove beneficial to some individuals with type 1 diabetes.

downloadThey have created a drug based on the GAD65 protein found in the insulin-producing beta cells. This new drug, called GAD-alum, is injected directly into the lymph nodes in the groin and may help the immune system become more tolerant of the body’s GAD proteins. The patients testing the GAD-alum were also given Vitamin D supplements to reduce the inflammatory response of the immune system.

The initial study was very small – just six patients – but researchers want to expand testing to more patients and follow them for longer periods of time. The six who participated were all between the ages of 20 and 22 and had been diagnosed with type 1 diabetes within six months prior to the study.

Johnny Ludvigsson, principal investigator of the study and a professor at Linköping University, was very excited about the results noting, “The results for these six patients are very promising. Type 1 diabetes usually progresses gradually as the patient loses the ability to produce insulin, but this has not happened in these patients. We must follow them for a longer period and we must include more patients before we can say anything about the effectiveness of the treatment, but the results so far are extremely exciting.”

All of the patients were followed for at least six months, and four were followed for more than 15 months. The results showed that their natural insulin production remained at stable levels and there was a decreased need for extra insulin injections. This could be very promising for the future of type 1 diabetes treatment, at least for some patients.

“If these results are confirmed when we test more patients, it would be an extremely important advance,” says Ludvigsson. “The way in which type 1 diabetes progresses differs between individuals for many reasons, and this means that it is not necessary to find a treatment that has excellent effects for everyone. Even if it helps only half of patients, this would be a major step forward.”

It is these types of small, innovative research studies that pave the way for more comprehensive studies and trials. The Diabetes Research Connection is committed to generating funding for early-career scientists with exciting ideas for the prevention, treatment, and cure of type 1 diabetes. Learn more about proposed studies and donate to support their progress online at Diabetes Research Connection.  

Learn More +

Type 1 Diabetes Produces Unique Inflammatory Signature in the Gut

Living with Type 1 diabetes means constantly being aware of what food is eaten and how it is broken down by the body. Since the pancreas produces little to no insulin on its own to support the management of blood sugar, this must be controlled through diet, exercise, and insulin injections. Researchers have long thought that the digestive tract and gut may play a role in Type 1 diabetes, but were unclear exactly how.

dt_140502_stomach_800x600A recent study conducted by the Diabetes Research Institute at San Raffaele Hospital in Milan, Italy, sheds some light on this hypothesis. Researchers examined the gastrointestinal tract of 54 people through endoscopies and biopsies of the first part of the small intestine. The tissue samples revealed valuable results.

According to Lorezno Piemonti, MD, senior author on the study, “Our findings indicate the individuals with Type 1 diabetes have an inflammatory signature and microbiome that differ from what we see in people who do not have diabetes or even in those with other autoimmune disorders such as celiac disease.”  Not only was there more inflammation of the mucous membrane in those with diabetes, but their gut bacteria also differed from those without diabetes or those with celiac disease.

As researchers take a closer look at the tissue samples, it stimulates further questions regarding the role of the gut on diabetes. Scientists are unsure whether the findings in the gut are “caused by or the result of the body’s own attacks on the pancreas,” says Piemonti. More in-depth research into the gastrointestinal tract and gut bacteria could lead to more targeted treatment for individuals with diabetes.

It is innovative research like this that Diabetes Research Connection is passionate about supporting. Scientists can receive funding for studies related to the prevention, treatment, or cure of Type 1 diabetes through the support of individuals and organizations that contribute to Diabetes Research Connection. Advancing research plays an instrumental role in changing the lives of those affected by Type 1 diabetes and every dollar counts. Visit us online to learn more.

Learn More +

Transplanted Cells Lead to Growth of New Pancreas: Another Step Toward Curing Diabetes?

There are around 1.25 million Americans living with Type 1 diabetes, and another 40,000 are diagnosed each year.  These numbers are even greater when Type 2 diabetes is added to the mix. A significant focus has gone into research for Type 1 diabetes, which occurs when the body does not produce insulin. One area that may hold hope involves pancreas transplants.

bigstock-Human-Gallbladder-and-Pancreas-83816423Currently there are more than 76,000 people waiting for transplants in the United States according to the U.S. Department of Health and Human Services. This is a complex process because it relies on organ donation and the organ must be a match for the recipient. While a pancreas transplant can cure diabetes in some patients, it also comes with risk of rejection and other complications, and there are only so many pancreases available.

Stem cell biologist Hiromitsu Nakauchi from Stanford University School of Medicine is working to alleviate this shortage through the growth of new organs. Nakauchi and his team successfully injected a rat embryo with pluripotent stem cells from a mouse. These are cells that can develop into any type of cell. Since the rat embryo had been modified to not grow a pancreas, these mouse cells developed into a mouse pancreas that could then be transplanted from the rat to the mouse.  Not only was it a functioning pancreas, it held the key for treating those with diabetes – it had insulin-secreting islet cells.

Furthermore, the mouse’s immune system was able to eliminate any stray rat cells that came along with the transplanted pancreas thereby greatly decreasing risk of rejection. Rather than prolonged use of immunosuppressive drugs, the mouse only needed these medications for five days following transplant. A year later, the pancreas was still functioning well with no signs of rat cells, tumors, or abnormalities. The mouse’s blood sugar had returned to normal as well.

A Long Road Ahead

This study is by no means an immediate solution. There is still a great deal of research that must be done. The idea is that eventually this technique could be used to grow human organs in larger animals such as pigs or sheep. There are a slew of ethical and medical concerns associated with this process, but it is a step toward advancing potential treatment options for the future.

“… there is a much greater evolutionary distance between humans and pigs or sheep than there is between mice and rats, and this could create challenges,” Nakauchi told Live Science. “So much more research needs to be done to ensure that this approach is both safe and effective.” But this study opens the door for new research and further investigation into the possibility of growing new organs and not only providing a potential cure for Type 1 diabetes, but also giving more people access to life-saving transplants for a variety of organs.

The Diabetes Research Connection stands alongside researchers in their quest to prevent, treat, and cure Type 1 diabetes by providing funding for studies led by early-career scientists. All donations go directly to the scientists and are tax-deductible. Help change the lives of those living with Type 1 diabetes by visiting Diabetes Research Connection to learn more about the cutting-edge research proposals and choose one (or more) to donate toward.

Learn More +
ETH Researchers T1D

New Weapon Against Diabetes

Original article published by ETH Zurich on December 1, 2016. Click here to read the original article.

Researchers have used the simplest approach yet to produce artificial beta cells from human kidney cells. Like their natural model, the artificial cells act as both sugar sensors and insulin producers.

Researchers led by ETH Professor Martin Fussenegger at the Department of Biosystems Science and Engineering (D-BSSE) in Basel have produced artificial beta cells using a straightforward engineering approach. These pancreatic cells can do everything that natural ones do: they measure the glucose concentration in the blood and produce enough insulin to effectively lower the blood sugar level. The ETH researchers presented their development in the latest edition of the journal Science.

Previous approaches were based on stem cells, which the scientists allowed to mature into beta cells either by adding growth factors or by incorporating complex genetic networks.

For their new approach, the ETH researchers used a cell line based on human kidney cells, HEK cells. The researchers used the natural glucose transport proteins and potassium channels in the membrane of the HEK cells. They enhanced these with a voltage-dependent calcium channel and a gene for the production of insulin and GLP-1, a hormone involved in the regulation of the blood sugar level.

Voltage switch causes insulin production

In the artificial beta cells, the HEK cells’ natural glucose transport protein carries glucose from the bloodstream into the cell’s interior. When the blood sugar level exceeds a certain threshold, the potassium channels close. This flips the voltage distribution at the membrane, causing the calcium channels to open. As calcium flows in, it triggers the HEK cells’ built-in signalling cascade, leading to the production and secretion of insulin or GLP-1.

The initial tests of the artificial beta cells in diabetic mice revealed the cells to be extremely effective: “They worked better and for longer than any solution achieved anywhere in the world so far,” says Fussenegger. When implanted into diabetic mice, the modified HEK cells worked reliably for three weeks, producing sufficient quantities of the messengers that regulate blood sugar level.

Helpful modelling

In developing the artificial cells, the researchers had the help of a computer model created by researchers working under Jörg Stelling, another professor in ETH Zurich’s Department of Biosystems Science and Engineering (D-BSSE). The model allows predictions to be made of cell behaviour, which can be verified experimentally. “The data from the experiments and the values calculated using the models were almost identical,” says Fussenegger.

He and his group have been working on biotechnology-based solutions for diabetes therapy for a long time. Several months ago, they unveiled beta cells that had been grown from stem cells from a person’s fatty tissue. This technique is expensive, however, since the beta cells have to be produced individually for each patient. The new solution would be cheaper, as the system is suitable for all diabetics.

Market-readiness is a long way off

It remains uncertain, though, when these artificial beta cells will reach the market. They first have to undergo various clinical trials before they can be used in humans. Trials of this kind are expensive and often last several years. “If our cells clear all the hurdles, they could reach the market in 10 years,” the ETH professor estimates.

Diabetes is becoming the modern-day scourge of humanity. The International Diabetes Federation estimates that more than 640 million people worldwide will suffer from diabetes by 2040. Half a million people are affected in Switzerland today, with 40,000 of them suffering from type 1 diabetes, the form in which the body’s immune system completely destroys the insulin-producing beta cells.
[su_button url=”https://www.ethz.ch/en/news-and-events/eth-news/news/2016/12/artificial-beta-cells.html?elqTrackId=3118751de0d340b8bf7c42cba3a3a7d2&elq=3ba510d3772545b28e0cfdf8c559795e&elqaid=17762&elqat=1&elqCampaignId=10602″ target=”blank” style=”flat” background=”#64b243″ size=”6″ center=”yes” radius=”5″ icon=”icon: angle-right”]Continue Reading[/su_button]

Learn More +
diabetes research

Economic 3D-Printing Approach for Transplantation of Human Stem Cell-Derived β-Like Cells

Original article published by IOP Science on December 1, 2016. Click here to read the original article.

Abstract

Transplantation of human pluripotent stem cells (hPSC) differentiated into insulin-producing βcells is a regenerative medicine approach being investigated for diabetes cell replacement therapy. This report presents a multifaceted transplantation strategy that combines differentiation into stem cell-derived β (SC-β) cells with 3D printing. By modulating the parameters of a low-cost 3D printer, we created a macroporous device composed of polylactic acid (PLA) that houses SC-β cell clusters within a degradable fibrin gel. Using finite element modeling of cellular oxygen diffusion-consumption and an in vitro culture system that allows for culture of devices at physiological oxygen levels, we identified cluster sizes that avoid severe hypoxia within 3D-printed devices and developed a microwell-based technique for resizing clusters within this range. Upon transplantation into mice, SC-β cell-embedded 3D-printed devices function for 12 weeks, are retrievable, and maintain structural integrity. Here, we demonstrate a novel 3D-printing approach that advances the use of differentiated hPSC for regenerative medicine applications and serves as a platform for future transplantation strategies.

[su_button url=”http://iopscience.iop.org/article/10.1088/1758-5090/9/1/015002/meta?elqTrackId=96062d779f46499eb7cc18d9ab30d665&elq=3d599e01edda49df92afa531a8a717ae&elqaid=17717&elqat=1&elqCampaignId=10609″ target=”blank” style=”flat” background=”#64b243″ size=”6″ center=”yes” radius=”5″ icon=”icon: angle-right”]Continue Reading[/su_button]

Learn More +
insulin

“Artificial Pancreas” Is Approved

Original article published by The JAMA Network on October 4, 2016. Click here to read the original article.

A new device that automatically monitors blood glucose levels and adjusts insulin levels has received FDA approval. The device, manufactured by Dublin-based Medtronic PLC, is the first such system to gain the agency’s blessing.

The new MiniMed 670G hybrid closed-loop system is intended for people aged 14 years or older who have type 1 diabetes. Because it operates with a smart algorithm that learns an individual’s insulin needs and delivers appropriate basal doses 24 hours a day, little user input is required. Patients who use the system will only have to enter their mealtime carbohydrates, accept bolus correction recommendations, and periodically calibrate the sensor.

[su_button url=”http://jamanetwork.com/journals/jama/article-abstract/2584035″ target=”blank” style=”flat” background=”#64b243″ size=”6″ center=”yes” radius=”5″ icon=”icon: angle-right”]Continue Reading[/su_button]

Learn More +
Diabetes Supplies - Bottles

Imbalance of Bacteriome Profiles Within the Finnish Diabetes Prediction and Prevention Study

Original article published by Wiley Online Library on August 22, 2016. Click here to read the original article.

Abstract

Background

We set out to explore associations between the stool bacteriome profiles and early-onset islet autoimmunity, taking into account the interactions with the virus component of the microbiome.

Methods

Serial stool samples were longitudinally collected from 18 infants and toddlers with early-onset islet autoimmunity (median age 17.4 months) followed by type 1 diabetes, and 18 tightly matched controls from the Finnish Diabetes Prediction and Prevention (DIPP) cohort. Three stool samples were analyzed, taken 3, 6, and 9 months before the first detection of serum autoantibodies in the case child. The risk of islet autoimmunity was evaluated in relation to the composition of the bacteriome 16S rDNA profiles assessed by mass sequencing, and to the composition of DNA and RNA viromes.

Results

Four operational taxonomic units were significantly less abundant in children who later on developed islet autoimmunity as compared to controls—most markedly the species of Bacteroides vulgatus and Bifidobacterium bifidum. The alpha or beta diversity, or the taxonomic levels of bacterial phyla, classes or genera, showed no differences between cases and controls. A correlation analysis suggested a possible relation between CrAssphage signals and quantities of Bacteroides dorei. No apparent associations were seen between development of islet autoimmunity and sequences of yet unknown origin.

Conclusions

The results confirm previous findings that an imbalance within the prevalent Bacteroidesgenus is associated with islet autoimmunity. The detected quantitative relation of the novel “orphan” bacteriophage CrAssphage with a prevalent species of the Bacteroides genus may exemplify possible modifiers of the bacteriome.

[su_button url=”http://onlinelibrary.wiley.com/doi/10.1111/pedi.12468/full” target=”blank” style=”flat” background=”#64b243″ size=”6″ center=”yes” radius=”5″ icon=”icon: angle-right”]Continue Reading[/su_button]

Learn More +
Measuring blood sugar

Presidential Proclamation — National Diabetes Month, 2016

Original article published by The President of the United States of America on October 28, 2016. Click here to read the original article.

More than 29 million Americans have diabetes — a disease in which the glucose levels in one’s blood are higher than normal. Although the rate of new cases is falling, the numbers are still alarming. Diabetes is one of the leading causes of death in the United States and results in staggering health and financial costs for Americans. With a concentrated effort to reduce the number of new diagnoses and improve treatment and care for those living with this disease, we must continue making progress in the battle against this epidemic. Each year during National Diabetes Month, we resolve to support everyone battling this chronic disease, and we recommit to fighting it so that more Americans can lead a healthy life.

 

[su_button url=”https://www.whitehouse.gov/the-press-office/2016/10/28/presidential-proclamation-national-diabetes-month-2016″ target=”blank” style=”flat” background=”#64b243″ size=”6″ center=”yes” radius=”5″ icon=”icon: angle-right”]Continue Reading[/su_button]

Learn More +
t1d research

Antibiotic-Mediated Gut Microbiome Perturbation Accelerates Development of Type 1 Diabetes in Mice

Original article published by PubMed on August 22, 2016. Click here to read the original article.

The early life microbiome plays important roles in host immunological and metabolic development. Because the incidence of type 1 diabetes (T1D) has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota, which predisposes to disease. Using non-obese diabetic mice that are genetically susceptible to T1D, we examined the effects of exposure to either continuous low-dose antibiotics or pulsed therapeutic antibiotics (PAT) early in life, mimicking childhood exposures. We found that in mice receiving PAT, T1D incidence was significantly higher, and microbial community composition and structure differed compared with controls. In pre-diabetic male PAT mice, the intestinal lamina propria had lower Th17 and Treg proportions and intestinal SAA expression than in controls, suggesting key roles in transducing the altered microbiota signals. PAT affected microbial lipid metabolism and host cholesterol biosynthetic gene expression. These findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression and T-cell populations, accelerating T1D onset in non-obese diabetic mice.

[su_button url=”https://www.ncbi.nlm.nih.gov/pubmed/27782139?dopt=Abstract&utm_source=twitterfeed&utm_medium=twitter#” target=”blank” style=”flat” background=”#64b243″ size=”6″ center=”yes” radius=”5″ icon=”icon: angle-right”]Continue Reading[/su_button]

Learn More +
insulin pen

In-Depth: Five innovators who see the future of connected insulin delivery in pens, not pumps

Original article published by Mobi Health News on October 21, 2016. Click here to read the original article.

Medtronic. Dexcom. Abbott. Sanofi. Google. A lot of very large, well-known companies are investing heavily into innovating the diabetes space, and that innovation is exciting. But a disproportionate amount of the innovation around insulin delivery focuses on the insulin pump, a delivery device that’s only used by a small percentage of insulin users. Most insulin users — between 70 and 93 percent, depending on whose figures you use and what part of the world you’re looking at — use an insulin pen, a device developed by Novo Nordisk in the eighties and relatively unchanged since then.

A small crop of startups has decided that it’s high time connected health innovation came to the insulin pen. One of the leaders of the pack — a San Diego startup called Companion Medical — is led by a veteran of those big company efforts. CEO Sean Saint previously worked at Medtronic, Dexcom, and Tandem Diabetes.

“Here I am at Tandem asking this question ‘How do we get more people to use the insulin pump?’” he told MobiHealthNews. “And that’s the right question for Tandem. So we’re asking questions like ‘Why will you or won’t you use an insulin pump?’ and we’re getting answers like tubing, cost, complexity that sort of thing. To be frank I was getting a little frustrated with the patient, and asking ‘Why won’t you use this great technology we’re developing?’”

That’s when Saint found himself on the other side of the pump: He was diagnosed with Type 1 diabetes.

“For me it caused me to look in the mirror and say ‘Stop being frustrated with people who won’t use your great technology. They have their reasons.’ Instead, let’s ask a different question. Let’s ask ‘How do we bring the benefits of insulin pumps to the 93 percent of people who use insulin who are pen and syringe users?’”

Companion Medical, with backing from Eli Lilly and Company, announced this past summer that it had FDA clearance to do just that. And in the months that followed, three other companies came out of stealth announcing that they were working on similar offerings. A fifth, Emperra, has been quietly developing its own smart insulin pen in Germany and will soon be ready to take it to other parts of the world.

First Patients Pending, a London company that had already innovated the insulin pen space with a non-connected cap called Timesulin, announced that it was working on a smartphone-connected product. Then an Irish group called Innovation Zed, which also had a pre-existing nonconnected insulin pen accessory, announced its plans to enter the space. And finally a second US company, Cambridge, Massachusetts-based Common Sensing, announced a trial funded by Sanofi and led by the Joslin Diabetes Center.

What all these companies have in common is they recognize that, though it might be the focus of big companies, the insulin pump is not the preferred device of the masses.

“We’ve talked to a lot of people in the space and what we’ve learned is that, first of all, not everyone prefers pumps,” James White, president of Common Sensing, told MobiHealthNews. “There’s people that have access to them and a lot of them choose not to use pumps. There’s people who want access and can’t get them. But we’re pretty sure for the next five to 10 years there is not a pump both for the market and everyone’s preferences, so there won’t be that ‘coming together’ to take any kind of authority in the market. We talk with pharma companies and we hear a fair amount of their predictions. And as nice as the pump is for some people, for a lot of people it just doesn’t make sense.”

Creating a connected insulin pen is a leap of several steps at a time. Unlike, say, fingerstick glucometers, which have always collected data but didn’t always store or transmit it, the traditional insulin pen doesn’t collect data at all. If patients want a record of how much insulin they used, they have to eyeball it and write it down. A connected pen is first and foremost an adherence play, but it can go much further — by interfacing with glucometer or CGM data or self-reported food data, a connected insulin pen could allow pen users to live some variant of the artificial pancreas dream, which up until now has only been a possibility for pump users.

“I believe that the insulin data is the most important data that we have,” Patients Pending CEO and cofounder John Sjölund told MobiHealthNews. “Currently, every time you turn the dial and inject yourself, it just disappears. All of the blood sugar and especially the CGMs, they exist, they’re good enough and the apps exist and they’re getting better. But the insulin information is just missing. And that’s the piece of the pie we bring out, and what’s important is the accuracy we bring to the table.”

From insulin adherence to insulin management

One way in which the various companies in this space differ is exactly what problem they’re using connectivity to solve. For most of the startups right now, the objective is simply to collect the data of how a often a patient uses an insulin pen and how much insulin they inject, and to use that data to drive adherence.

“The [device] we announced this week is the first step, we’re tackling that 60 to 70 percent adherence rate of insulin users,” John Hughes, CEO of Innovation Zed, told MobiHealthNews. “The insulin user audience are at a very low level of compliance. You show up at the doctor and inevitably when you get there, you don’t have your records. They’re working on anecdotal data. We have focus groups [of doctors] that we work with and they tell us, they cannot trust the data that they’re getting.”

The most basic advantage of tracking pen usage doesn’t require connectivity at all. Patients Pending’s original product, Timesulin, is a cap for insulin pens that starts a timer when it’s removed and replaced, so that patients can always look at it and see when their most recent dose was. Even this is useful information that can help prevent double dosing.

Adding connectivity also allows a device to send alerts about a missed dose to the patient’s smartphone, or to alert a patient’s physician, caregiver, or coach when they miss a dose. That’s where James White, president of Common Sensing, sees the initial value of the technology.

“Right now, people go home from the doctor after being given insulin for the first time and they don’t have another touchpoint for three months with anything,” he told MobiHealthNews. “Their data is theirs, they’re looking at it, they often don’t know how to interpret it because they weren’t taught at the doctor, and more than half of those people, in those first three months, drop off. They come back and they’re not using it. They haven’t filled all their prescriptions, things like that. The reasons vary a ton. Sometimes people aren’t prescribed needles to use with their insulin pen. Some people don’t know how to use it, they’re afraid to inject something new, or they don’t remember the instructions.”

Common Sensing’s Gocap is focused on collecting the data and sending it to a smartphone app, from whence it can also be sent to a data aggregator or a caregiver. The company is looking into developing its device for different levels of tech savvy: some use cases might allow for more patient engagement while others are designed to be more passive.

“We’ve sent this home now with a fair number of people and we’ve seen a wide spectrum. Some people don’t have a smartphone, they want to keep a very cheap mobile data device plugged into the wall and never look at it and use this hardware device. They know the data’s going somewhere, to their doctor, and that’s all they care about,” he said. “And then some people are the power users, just like any product. They want to get into the data, enable that exact setting, see every new dose they’ve done, understand the accuracy and the glucose readings.”

As an adherence play, the space is very reminiscent of another medication delivery device that’s recently blossomed into a burgeoning industry in digital health: the connected, sensor-laden inhaler. After some early success by companies like Propeller Health, the connected inhaler space rapidly became a hot acquisition target for the pharmaceutical industry. The comparison isn’t lost on insulin pen innovators.

“What I like about insulin and why we made it a first target for the company is that right now, you know, inhalers can be expensive when they’re taken incorrectly, but the cost burden on the healthcare system right now of incorrect insulin use is far greater than any other medication,” White said. “Pharma right now loses on the order of a third of revenue they could be getting just because a third of prescriptions are never picked up. And not only that but among people who are using it it’s not being used very effectively. So a company that can differentiate in making their insulin more effective stands to benefit, and that’s why companies like Sanofi are interested.”

So far at least two major pharma companies have invested in this space: Sanofi has invested in Common Sensing and Lilly has invested in Companion Medical. Neither of those investments has “strings attached” according to the two companies, but the interest is certainly notable.

But Sean Saint, of Companion, sees the insulin pen space as being much deeper than the inhaler space.

“The connected inhaler market is a compliance tool,” he said. “And that’s wonderful, because we all know about compliance problems. And we have 100 percent of that benefit. Same exact thing. But one of the biggest problems in diabetes is not that I don’t remember to take my dose, but how much do I take? I know my blood sugar, I know what I have recently eaten and my recent insulin doses, so how much insulin do I take right now? That’s what a dose calculator provides and we are the only company I am aware of in the connected pen/cap space that has a dose calculator and certainly the only one cleared by FDA.”

That’s why Companion Medical has FDA 510(k) clearance while some of the other companies are holding off. (Common Sensing is registered with the FDA but White doesn’t believe it’s current adherence-focused offering requires premarket approval). By taking the next step and offering a dose calculator, and starting to offer advice on how much insulin a patient could take, the company enters a new risk category, but also potentially offers even more benefits to people with diabetes.

Saint’s company’s goal is to create a learning dose calculator, which will use the same kind of algorithms closed-loop “artificial pancreas” systems use, but with a connected pen rather than a pump as the delivery method.

“You can call it a poor man’s artificial pancreas or artificial pancreas light or whatever you want to call it, but it’s basically using the same algorithms and applying them to mobile injection therapy,” he said. “Nobody’s ever done that, so nobody knows what the ultimate clinical benefit of that will be, but we know that there will be one.”

For Patients Pending and Common Sensing, that functionality could be in the cards eventually, but they don’t see a reason to reinvent the wheel. Once the data is accurately collected and sent to a smartphone, third party apps can focus on making it actionable for the user.

“We’ve had a lot of experience developing software, but we’ve also learned how tricky healthcare and medical apps is,” Patients Pending’s Sjölund said. “And there are a lot of apps in the space already.”

Pens, caps, and wraps

Another differentiating factor between the various companies is the form factor. Only two of the five companies make a full-on insulin pen, two make smart pen caps, and one, Innovation Zed, makes a unique wraparound device that fits on the back part of the pen.

There are different facets to the decision. One is that, most companies agree, creating an entire insulin pen is a more daunting endeavor than creating an add-on.

“At first we thought, hey let’s build a digital pen,” Innovation Zed’s John Hughes told MobiHealthNews. “Not being very experienced in medical device market we were quickly put off by the regulatory implications of such a device. We thought, it will take us seven years to do that. So we came up with the concept of an add-on technology.”

Saint, at Companion, echoed these sentiments, though his company did decide to go down the full pen road (as did Emperra in Germany).

“One thing I can absolutely assure you: we did not design a full insulin pen instead of a cap because we thought it would be fun,” he said. “We considered the different solutions and we decided that the only way we could provide a solution to the patient that was going to be truly transparent to their current therapy was to control the whole experience. And that’s why we went with the pen.”

Controlling the whole device simplifies the design of the sensors and allows Companion Medical to include a larger battery — their device will last a year with no need to plug in or replace batteries, compared to Common Sensing’s cap, which will have to be plugged in once a week (though White says they’re also working on a version with a longer-term battery). It also allows for some complex features, like compensating for inaccuracies that can be caused by priming the pen (activating it without dosing to eliminate air bubbles).

On the other hand, add-on solutions have some added convenience in the market. While Companion’s device will replace a durable pen, other devices can work with disposable insulin pens, which are currently more popular.

“We diabetics are a pretty conservative lot and we don’t like changing our habits,” Innovation Zed’s Hughes said. “So when we get used to insulin pens we want to keep them. So we offer them a sleeve that wraps around the pen and a timer devices that clips on to the sleeve and is triggered only when the injection is completed.”

Saint thinks the additional value will be enough to persuade patients to change their habits. Caps are also likely cheaper to produce, but that could be a moot point if health insurers start routinely reimbursing for the devices.

The path to market and reimbursement

Although the space is just starting to emerge into public consciousness, the players have been working quietly on it for years, and now the race to market is on.

One company, Emperra, has a big lead, but it has only focused on its native Germany. It’s CE-marked Esysta pen is already on the market in Germany and reimbursable by German payers.

“We are on the market,” Emperra CEO Christian Krey told MobiHealthNews in an email. “It is working and has proved success. We are reimbursed by all health insurers in Germany. We have a unique software, that connects patients, relatives, nurses and physicians with high secured servers. We have unique contracts with health insurers that pay not only for the hardware, but also for data sharing between patient and the physician as well as for coaching the patients, depending on their needs.”

He also said the company has “proven success in a field trial together with a health insurer, that the use of the ESYSTA system leads to significant lowering of HbA1c without more usage of insulin.”

Emperra is already making inroads in the rest of the EU and in the US. The company has filed for FDA approval and hopes to enter the US market next year.

Innovation Zed also has trial data showing its product improves HbA1c, thanks to a partnership with the UK’s NHS. The Irish company also has a joint venture with Swedish injectables manufacturer SHL Group that could help them bring their new solution to market quickly once it’s fully developed. They’re targeting a 2017 European launch for the connected product and eyeing the US shortly thereafter. They are hoping for reimbursement from national systems like the NHS and from private payers in the US.

Common Sensing recently announced a clinical trial with Joslin Diabetes Center. Their product is ready to go, White says.

“The device is ready now, so what we’re looking for is the most efficient way to commercialize it with those services to insurers, self-insured employers, etc.,” he said.

Similarly, Companion Medical’s Sean Saint says his company is planning for commercialization in 2017, having been focused up until now on the FDA clearance.

“Smart pens are not a category yet,” he said. “We have the first cleared smart pen, and we’re going to be in the unenviable position of starting to figure out pricing on that. Pricing what amounts to a new category of devices can be very challenging. On the one hand, we have the negative that we look a lot like a traditional insulin pen. On the other hand we have the positive that we believe we offer a very significant clinical benefit over and above traditional insulin pens and potentially as much as a pump. So certainly the pricing will be in between traditional insulin pens and pumps. But I can’t tell you exactly where at this point.”

He says there will be some work to do for reimbursement, but he’s confident that the device will eventually be covered via the pharmacy benefit of a prescription drug plan. White agrees that reimbursement is inevitable.

“The general idea is we don’t want people to have to pay for this out of pocket,” he said. “The idea that patients are causing the problem right now is one that shouldn’t really exist in any modern society. And that means that patients shouldn’t be responsible for fixing this problem in terms of paying for their own medicine. So in our minds, the people who stand to gain the most from this are insurance companies and pharma companies. If someone switches from taking their insulin to not taking their insulin, in the next year they will probably cost on the order of $2,500 more per year and the insurer’s paying for all of that.”

Innovation in the diabetes space is coming in a lot of forms from a lot of places, from the artificial pancreas, to AI coaching, to glucose-sensing contact lenses. But when it comes to making a big difference right now in the lives of many insulin-using type 1 diabetics, smart pens might just be the next big thing. As Saint pointed out, the market is so much larger for pens that even a modest improvement in diabetes management could help a lot of people.

“The health economics of smart pens are phenomenal when you start to think about them,” he said.

[su_button url=”http://www.mobihealthnews.com/content/depth-five-innovators-who-see-future-connected-insulin-delivery-pens-not-pumps?mkt_tok=eyJpIjoiTW1Vd056UTBOR1kyTlRndyIsInQiOiJKbkRadjFnbGdXOTR1UVwvNTJsZFNGanNDaXc5Ylo0bGhycEhjSnVcL2RNWlFUWFRcL3Y3WUp6TFRwaVA5TTQ0QzFyVXU5SVNhblwvdGw5REZSYk5jWTZUeGpMcGdBVzl4NnVLS2J1bXlTbW1DdEU9In0%3D” target=”blank” style=”flat” background=”#64b243″ size=”6″ center=”yes” radius=”5″ icon=”icon: angle-right”]Continue Reading[/su_button]

Learn More +
Single-Cell Mass Cytometry Analysis of the Human Endocrine Pancreas

Single-Cell Mass Cytometry Analysis of the Human Endocrine Pancreas

Original article published by Cell Press on October 11, 2016. Click here to read the original article.

Highlights

  • Mass cytometry promotes high-throughput phenotyping of islets at a single-cell level
  • Alpha cells maintain higher basal proliferation and are more responsive to mitogens
  • Beta cells exist in distinct states

Summary

The human endocrine pancreas consists of multiple cell types and plays a critical role in glucose homeostasis. Here, we apply mass cytometry technology to measure all major islet hormones, proliferative markers, and readouts of signaling pathways involved in proliferation at single-cell resolution. Using this innovative technology, we simultaneously examined baseline proliferation levels of all endocrine cell types from birth through adulthood, as well as in response to the mitogen harmine. High-dimensional analysis of our marker protein expression revealed three major clusters of beta cells within individuals. Proliferating beta cells are confined to two of the clusters.

[su_button url=”http://www.cell.com/cell-metabolism/abstract/S1550-4131(16)30486-7?elqTrackId=6789327ac64b42228e73a1532b63e754&elq=d19a63a48c4c401c9e53b0028684553c&elqaid=16965&elqat=1&elqCampaignId=9″ target=”blank” style=”flat” background=”#64b243″ size=”6″ center=”yes” radius=”5″ icon=”icon: angle-right”]Continue Reading[/su_button]

Learn More +
DRC

U.S. FDA approves Medtronic’s ‘artificial pancreas’ for diabetes

Original article published by Yahoo! Finance. Click here to read the original article.

Medtronic Plc won U.S. approval on Wednesday for an “artificial pancreas” that is the first device to automatically deliver the right dose of insulin to patients with type 1 diabetes, freeing them from continually monitoring insulin levels throughout each day.

The U.S. Food and Drug Administration, in its approval of the device, the MiniMed 670G, hailed it as a breakthrough.

The device offers type 1 diabetics “greater freedom to live their lives without having to consistently and manually monitor baseline glucose levels and administer insulin,” Dr. Jeffrey Shuren, director of the FDA’s medical device division, said in a statement.

Analysts said the FDA approved the device six months sooner than expected. However, it will not be available until the spring of 2017.

The MiniMed 670G is the first device that allows a glucose sensor to communicate with an insulin pump and automatically regulate the insulin flow. The device is approved for those aged 14 and older.

The device measures glucose levels every five minutes and automatically administers insulin as needed. Patients will still need to instruct the device to deliver extra insulin for meals and notify the device when they exercise – which lowers glucose levels.

About 1.25 million American children and adults have type 1 diabetes, a condition in which the pancreas produces little or no insulin – a hormone needed to obtain energy from food.

Patients take insulin injections at various times of the day. But blood sugar can drop to dangerously low levels if too much insulin circulates in the bloodstream, requiring patients to frequently or continually monitor their insulin levels throughout the entire day.

“This device will mean peace of mind, in knowing a person will be in normal blood sugar range a great majority of the time,” said Derek Rapp, chief executive officer of the Juvenile Diabetes Research Foundation, which has spent $116 million on research in the artificial pancreas field.

Rapp, who has a college-age son with type 1 diabetes, said his son as a child had to be awakened many times each evening so his finger could be pricked for a blood sample, to ensure his blood sugar level was in an acceptable range. If too low, his son would be given fruit juice or a snack. If too high, he would be given insulin.

“It is a major news event that a system of this kind has been approved – the first time a pump will administer insulin as a result of information it receives from a sensor,” Rapp said.

The Medtronic device includes a coin-size sensor with a protruding needle that is slipped under the skin and continually monitors glucose levels. It is held in place with a sticky backing. The other main component is an insulin pump, often worn on the side of the abdomen, which has tubes that lead to a catheter that delivers the insulin.

Insulin pumps are currently used by more than a third of U.S. patients with type 1 diabetes, but they require manual adjustment to administer the needed insulin dose. Many patients also wear sensors that continually monitor their glucose levels.

Several insulin pump makers, including Johnson & Johnson , Tandem Diabetes Care Inc and Insulet Corp , are teaming up with sensor maker Dexcom Inc to develop devices like Medtronic’s but are several years behind, according to Jefferies analyst Raj Denhoy.

He said the Medtronic system is a big step for patients, but the Holy Grail would be a completely automatic artificial pancreas that does not need any intervention, including for meals or exercise. Such a product is probably at least five years away from development, he said.

Although Medtronic has not announced a price for the MiniMed 670G, Denhoy estimated it may cost $5,000 to $8,000, with the annual cost of disposable sensors another few thousand dollars.

[su_button url=”http://finance.yahoo.com/news/u-fda-approves-medtronics-artificial-185726604.html” target=”blank” style=”flat” background=”#64b243″ size=”6″ center=”yes” radius=”5″ icon=”icon: angle-right”]Continue Reading[/su_button]

Learn More +
t1d research

Safety of a Hybrid Closed-Loop Insulin Delivery System in Patients With Type 1 Diabetes

Original article published by The Journal of the American Medical Association. Click here to read the original article.

Closed-loop artificial pancreas technology uses a control algorithm to automatically adjust insulin delivery based on subcutaneous sensor data to improve diabetes management. Currently available systems stop insulin in response to existing or predicted low sensor glucose values, whereas hybrid closed-loop systems combine user-delivered premeal boluses with automatic interprandial insulin delivery. This study investigated the safety of a hybrid closed-loop system in patients with type 1 diabetes.

Methods

Patients aged 14 to 75 years with type 1 diabetes for at least 2 years, glycated hemoglobin (HbA1c) less than 10%, and more than 6 months of insulin pump use were recruited from 10 centers (9 in the United States, 1 in Israel) between June 2, 2015, and November 11, 2015. This before and after study had a 2-week run-in period (baseline) for patients to learn the devices without the automated features followed by a 3-month study period with the initial 6 days used to collect insulin and sensor glucose data for the hybrid closed-loop algorithm. In the study period, there was a 6-day hotel stay during which 1 day was used for frequent sampling of venous blood glucose to verify the accuracy of the system. The last patient visit was March 7, 2016. Two central and 4 local institutional review boards approved the study. Written informed consent was obtained from adults and parents, and written assent from minors.

The system included investigational continuous glucose monitoring sensors with transmitters, insulin pumps displaying real-time glucose data, a proprietary algorithm, and blood glucose meters. Patients were required to periodically calibrate sensors and enter carbohydrate estimates for meal boluses. Every midnight, multiple parameters were automatically adjusted by the algorithm.

Safety end points obtained during the run-in and study periods (including the hotel stay) were the incidence of severe hypoglycemia and diabetic ketoacidosis, serious adverse events, and device-related serious and unanticipated adverse events. Prespecified descriptive end points included time in open vs closed-loop systems; the percentage of sensor glucose values below, within, and above target range (71-180 mg/dL), including at night time; changes in HbA1c, insulin requirements and body weight; and measures of glycemic variability. End points were collected during both periods and analyzed with SAS(SAS Institute), version 9.4.

Results

Of the 124 participants (mean age, 37.8 years [SD, 16.5]; men, 44.4%), mean diabetes duration was 21.7 years, mean total daily insulin dose was 47.5 U/d (SD, 22.7), and mean HbA1c was 7.4% (SD, 0.9). Over 12 389 patient-days, no episodes of severe hypoglycemia or ketoacidosis were observed. There were 28 device-related adverse events that were resolved at home. There were 4 serious adverse events (appendicitis, bacterial arthritis, worsening rheumatoid arthritis, Clostridium difficile diarrhea) and 117 adverse events not related to the system, including 7 episodes of severe hyperglycemia due to intercurrent illness or other nonsystem causes.

The system was in closed-loop mode for a median of 87.2% of the study period (interquartile range, 75.0%-91.7%). Glycated hemoglobin levels changed from 7.4% (SD, 0.9) at baseline to 6.9% (SD, 0.6) at study end . From baseline to the end of the study, daily dose of insulin changed from 47.5 U/d to 50.9 U/d, and weight changed from 76.9 kg to 77.6 kg. The percentage of sensor glucose values within the target range changed from 66.7% at baseline to 72.2% at study end. Sensor and reference glucose values collected during the hotel stays were in good agreement, with an overall mean absolute relative difference of 10.3% (SD, 9.0).

Discussion

To our knowledge, this is the largest outpatient study to date and it demonstrated that hybrid closed-loop automated insulin delivery was associated with few serious or device-related adverse events in patients with type 1 diabetes. Limitations include lack of a control group, restriction to relatively healthy and well-controlled patients, the relatively short duration, and an imbalance between the length of the study periods. Differences in HbA1c levels may be attributable to participation in the study. A similar study in children is under way. Longer-term registry data and randomized studies are needed to further characterize the safety and efficacy of the hybrid closed-loop system.

[su_button url=”http://jama.jamanetwork.com/article.aspx?articleid=2552454″ target=”blank” style=”flat” background=”#64b243″ size=”6″ center=”yes” radius=”5″ icon=”icon: angle-right”]Continue Reading[/su_button]

Learn More +
continuous glucose monitoring

Does CGM Benefit Injection Users? Yes! Results from Dexcom’s DIaMonD Study

Original article published by diaTribe. Click here to read the original article.

Continuous glucose monitoring (CGM) is often considered a technology for insulin pump users – not those on injections. New results from Dexcom’s DIaMonD study, presented at the ADA Scientific Sessions, will hopefully change that.

DIaMonD examined if the addition of CGM in those on multiple daily injections (MDI) could help improve blood sugar control. In this six-month study, participants with an average starting A1c of 8.6% were given either “usual care” (fingersticks alone) or the use of CGM for 24 weeks, measuring changes in A1c, time-in-range, and other outcomes. MDI users that added CGM saw a meaningful reduction in A1c of 0.9%, compared to a 0.4% improvement in the fingersticks (control) group. CGM also cut hypoglycemia by 30% (23 fewer minutes per day) and reduced time spent over 180 mg/dl by 83 minutes per day, far exceeding results in the control group.

Dr. Howard Wolpert (Joslin Diabetes Center) summarized the implications of the DIaMonD study, asserting that healthcare providers should consider recommending CGM to ALL patients with type 1 diabetes who have not attained their glucose goals – not just those on insulin pumps. This would be a major change from current trends, where only ~7% of MDI users with type 1 diabetes use CGM in the T1D Exchange registry.

DIaMonD adds to the evidence that CGM improves time-in-range, reduces highs and lows, and improves A1c. This does not come as a surprise since glucose value and trend can be observed every five minutes and alarms sound for lows and highs, allowing people to recognize patterns, tighten the feedback loop, and take action to improve. We expect this technology to only improve as apps and software make CGM data more useful – particularly for those not on pumps.

[su_button url=”https://diatribe.org/does-cgm-benefit-injection-users-yes-results-dexcoms-diamond-study” target=”blank” style=”flat” background=”#64b243″ size=”6″ center=”yes” radius=”5″ icon=”icon: angle-right”]Continue Reading[/su_button]

Learn More +
type 1 diabetes mortality study

Mortality in Type 1 Diabetes in the DCCT/EDIC Versus the General Population

Original article published by Diabetes Care. Click here to read the original article.

Objective

Historically, mortality in type 1 diabetes has exceeded that in the general population.
We compared mortality in the Diabetes Control and Complications Trial/
Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study
cohort to that of the current general U.S. population.

Research Design and Methods

The DCCT (1983–1993) compared intensive versus conventional therapy, with
HbA1c levels of ∼7 vs. 9%, respectively, over an average of 6.5 years of treatment.
EDIC is the observational follow-up study of the DCCT (1994 to the present). Vital
status was ascertained for 97.5% of the original DCCT cohort (n = 1,441) after a
mean of 27 years follow-up. Expected mortality during DCCT/EDIC was estimated
using the current age-, sex-, and race-specific risks in the general U.S. population,
and the observed versus expected mortality compared using standardized mortality
ratios (SMRs) and Poisson regression models.

Results

Mortality in the DCCT intensive therapy group was nonsignificantly lower than
that in the general U.S. population (SMR = 0.88 [95% CI 0.67, 1.16]), whereas
mortality in the DCCT conventional therapy group was significantly greater than
that in the general population (SMR = 1.31 [95% CI 1.05, 1.65]). The SMR increased
with increasing mean HbA1c, and above an HbA1c of 9%, the rate of increase in SMR
among females was greater than that among males.

Conclusions

Overall mortality in the combined DCCT/EDIC cohort was similar to that of the
general population but was higher in the DCCT conventional therapy group. Mortality
increased significantly with increasing mean HbA1c, more so among females
than males, especially for HbA1c >9%.

[su_button url=”http://care.diabetesjournals.org/content/diacare/39/8/1378.1.full.pdf” target=”blank” style=”flat” background=”#64b243″ size=”6″ center=”yes” radius=”5″ icon=”icon: angle-right”]Continue Reading[/su_button]

Learn More +

Research suggests that diabetes could be due to failure of beta cell ‘hubs’

Original article published by University of Birmingham on July 21, 2016. Click here to read the original article.

The significant role of beta cell ‘hubs’ in the pancreas has been demonstrated for the first time, suggesting that diabetes may due to the failure of a privileged few cells, rather than the behaviour of all cells.

Researchers used optogenetic and photopharmacological targeting to precisely map the role of the cells required for the secretion of insulin.

The team believe that the findings, published in Cell Metabolism, could pave the way for therapies that target the ‘hubs’.

Dr David Hodson, from the University of Birmingham, explained, “It has long been suspected that ‘not all cells are equal’ when it comes to insulin secretion. These findings provide a revised blueprint for how our pancreatic islets function, whereby these hubs dictate the behaviour of other cells in response to glucose.”

According to the NHS, there are currently 3.9 million people living with diabetes in the UK, with 90% of those affected having type 2 diabetes.

Type 2 diabetes occurs when the pancreas fails to produce enough insulin to function properly, meaning that glucose stays in the blood rather than being converted into energy.

Beta cells (β cells) make up around 65-80% of the cells in the islets of the pancreas. Their primary function is to store and release insulin and, when functioning correctly, can respond quickly to fluctuations in blood glucose concentrations by secreting some of their stored insulin.

These findings show that just 1-10% of beta cells control islet responses to glucose.

Dr Hodson, who is supported by Diabetes UK RD Lawrence and EFSD/Novo Nordisk Rising Star Fellowships, continued, “These specialised beta cells appear to serve as pacemakers for insulin secretion. We found that when their activity was silenced, islets were no longer able to properly respond to glucose. “

Prof Guy Rutter, who co-led the study at Imperial College London, added “This study is interesting as it suggests that failure of a handful of cells may lead to diabetes”.

Studies were conducted on islet samples from both murine and human models.

The team noted that, though the findings present a significant step forward in understanding the cell mechanisms, the experiments therefore may not be reflected in vivo, where blood flow direction and other molecule dynamics may influence the role of the hubs and insulin secretion.

Learn More +
Laboratory Equipment - microscope

New Approach for Regenerative Therapy

Original article published by HelmholtzZentrum munchen on June 12, 2016. Click here to read the original article.

Neuherberg, June 12, 2016. The marker Flattop subdivides the insulin-producing beta cells of the pancreas into those that maintain glucose metabolism and into immature cells that divide more frequently and adapt to metabolic changes. This could provide a starting point for regenerative diabetes therapies, as scientists of Helmholtz Zentrum München, in collaboration with colleagues of the Technical University of Munich and the German Center for Diabetes Research (DZD), report in the journal ‘Nature’.

The beta cells of the pancreas produce the metabolic hormone insulin when blood glucose levels rise, in order to keep glucose levels in equilibrium. If the beta cells are destroyed or lose their function, this can lead to serious diseases such as diabetes. However, not all beta cells are identical. “It has long been known that there are different subpopulations of beta cells,” said Professor Heiko Lickert, director of the Institute of Diabetes and Regeneration Research at Helmholtz Zentrum München. “But until now, the underlying molecular mechanisms have remained elusive.”

Flattop is a marker for mature beta cells

In the current study, the researchers led by Lickert searched for molecular markers subdividing the respective subgroups. One molecule, in particular, captivated their attention: the protein Flattop.* It was present in about 80 percent of all beta cells. These cells effectively determined the glucose concentration of their environment and secreted the corresponding amount of insulin, thus showing the metabolic properties of mature beta cells.

Cells without Flattop proliferate more frequently

Conversely, the team of researchers observed that beta cells in which no Flattop was measurable showed a particularly high rate of proliferation. “In our experimental model, these cells proliferated up to four times more often than the Flattop-positive cells,” said study leader Lickert.

A type of precursor cells?

To pursue the hypothesis that the actively dividing cells (without Flattop) could be precursors of metabolically active cells, the scientists made use of a genetic trick to map the fate of single cells. This so called lineage tracing revealed that the proliferative progenitor cells were able to develop into mature beta cells with metabolic properties. This was also the case, when the scientists placed them in an artificial mini-organ-like 3D environment. Moreover, genetic analyses confirmed that in beta cells without Flattop, primarily genes responsible for sensing the environment were expressed, while in cells with Flattop primarily classic metabolic programs took place.

“Our results suggest that the Flattop-negative cells are a kind of immature reserve pool, which constantly renews itself and can replenish the mature beta cells,” Lickert said. According to the study leader this new possibility of subdividing these two subgroups allows a comprehensive analysis of the signaling pathways involved. The results of the researchers raise hopes for the development of regenerative therapies: “The heterogeneity of the beta cells has been studied for more than 50 years, now with enabling technologies it looks like we are beginning to understand how the cells behave,“ said Lickert.

In the future, the scientist will focus on two major aspects: on the one hand in terms of regenerative therapy their goal would be to regenerate endogenous beta cells in a targeted manner to replace dysfunctional or lost cells in patients. On the other hand the findings are a milestone in the generation of functional beta cells from stem cells in cell culture for cell replacement therapy, which was not possible so far.

Further Information

Background:
* Flattop is part of the Wnt signaling pathway, which in particular regulates the development of tissues and cell functions.

**Lineage tracing is a method to map the fate of single cells. It is based on gene variants emitting a color signal upon induction of the respective gene. In this particular case cells without Flattop were colored in red and turned into green upon Flattop induction.

Original Publication:
Bader, E. et al. (2016). Identification of proliferative and mature β-cells in the islet of Langerhans, Nature, DOI: 10.1038/nature18624

Corresponding reviews of the research group:
Migliorini, A. et al. (2016). Impact of islet architecture on beta cell heterogeneity, plasticity and function, Diabetologia, doi: 10.1007/s00125-016-3949-9

Roscioni, S. et al. (2016). Impact of islet architecture on beta cell heterogeneity, plasticity and function, Nature Reviews Endocrinology, in press

The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members.

The research activities of the Institute of Diabetes and Regeneration Research (IDR) focus on the biological and physiological study of the pancreas and/or the insulin producing beta cells. Thus, the IDR contributes to the elucidation of the development of diabetes and the discovery of new risk genes of the disease. Experts from the fields of stem cell research and metabolic diseases work together on solutions for regenerative therapy approaches of diabetes. The IDR is part of the Helmholtz Diabetes Center (HDC).

Technical University of Munich (TUM) is one of Europe’s leading research universities, with more than 500 professors, around 10,000 academic and non-academic staff, and 39,000 students. Its focus areas are the engineering sciences, natural sciences, life sciences and medicine, reinforced by schools of management and education. TUM acts as an entrepreneurial university that promotes talents and creates value for society. In that it profits from having strong partners in science and industry. It is represented worldwide with a campus in Singapore as well as offices in Beijing, Brussels, Cairo, Mumbai, San Francisco, and São Paulo. Nobel Prize winners and inventors such as Rudolf Diesel, Carl von Linde, and Rudolf Mößbauer have done research at TUM. In 2006 and 2012 it won recognition as a German “Excellence University.” In international rankings, TUM regularly places among the best universities in Germany.

The German Center for Diabetes Research (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Zentrum München – German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich.

Learn More +
Diabetes testing

Even Short-Term T2DM Remission Reduces Risk of Microvascular Dz

Original article published by Medical News Today on June 14, 2016. Click here to read the original article.

TUESDAY, June 14, 2016 (HealthDay News) — For patients with type 2 diabetes, remission after bariatric surgery is associated with a reduced risk of microvascular disease, even after subsequent relapse, according to a study published online June 6 in Diabetes Care.

Karen J. Coleman, Ph.D., from Kaiser Permanente Southern California in Pasadena, and colleagues conducted a retrospective observational cohort study involving 4,683 patients with type 2 diabetes who underwent bariatric surgery from 2001 through 2011. The correlation between type 2 diabetes remission/relapse status and the time to microvascular disease was assessed.

The researchers found that, compared with patients who never remitted, patients who experienced type 2 diabetes remission had a lower risk of incident microvascular disease (hazard ratio, 0.71). For patients who experienced a relapse after remission there was an inverse relationship between the length of time spent in remission and the risk of incident microvascular disease; the risk of microvascular disease was reduced for every additional year of time spent in remission prior to relapse (hazard ratio, 0.81), compared with patients who never remitted.

“Our results indicate that remission of type 2 diabetes after bariatric surgery confers benefits for risk of incident microvascular disease even if patients eventually experience a relapse of their type 2 diabetes,” the authors write.

Full Text (subscription or payment may be required)

Learn More +
insulin shot

Type 1 Diabetes May be Triggered by Bacteria

Original article published by Medical News Today on May 17, 2016. Click here to read the original article.

Study co-author Dr. David Cole, of the School of Medicine at Cardiff, and colleagues –

The researchers recently published their findings in The Journal of Clinical Investigation.

Type 1 diabetes accounts for around 5 percent of all diabetes cases. Previously known as “juvenile diabetes,” the condition is most commonly diagnosed in children and young adults.

Type 1 diabetes arises when the body is unable to produce insulin – the hormone responsible for regulating blood glucose levels.

Killer T cells have high ‘cross-reactivity’

While the precise cause of type 1 diabetes is unclear, past research has shown that the condition occurs when killer T cells destroy beta cells – the cells in the pancreas that produce insulin.

In a previous study, Prof. Sewell and colleagues found high “cross-reactivity” among killer T cells, meaning that they can react to numerous triggers, including pathogens.

“Killer T cells sense their environment using cell surface receptors that act like highly sensitive fingertips, scanning for germs,” explains Dr. Cole.

“However, sometimes these sensors recognize the wrong target, and the killer T cells attack our own tissue. We, and others, have shown this is what happens during type 1 diabetes when killer T cells target and destroy beta cells.”

Once these beta cells are destroyed, insulin is no longer produced, meaning patients will require lifelong insulin therapy in order to control blood glucose levels.

Study sheds light on how killer T cells turn ‘rogue’

In their new study, the researchers suggest they may have uncovered a possible cause of type 1 diabetes, after finding that bacteria may spur killer T cells to attack beta cells.

The researchers identified a part of a bacterium that activates killer T cells, causing them to bind to beta cells and kill them.

“This finding sheds new light on how these killer T cells are turned into rogues, leading to the development of type 1 diabetes,” notes Dr. Cole.

The researchers say they hope their results will pave the way for new strategies to diagnose, prevent, and treat type 1 diabetes.

“We still have much to learn about the definitive cause of type 1 diabetes and we know that there are other genetic and environmental factors at play.

This research is significant as it pinpoints, for the first time, an external factor that can trigger T cells that have the capacity to destroy beta cells.”

As well as helping to understand what contributes to the development of type 1 diabetes, the researchers say their findings may also shed light on the causes of other autoimmune conditions.

Learn More +
microscope close up

Type 1 Diabetes Researchers Solve Immune System Mystery

On April 25, 2016, scientists from the University of Lincoln, led by Dr. Michael Christie, announced that they had identified a previously unknown molecule attacked by the immune system in those with type 1 diabetes.

This is incredibly important for prevention and treatment of the disease, as it could lead to better identification of those at risk of developing type 1 diabetes and guide the development of new therapies to prevent the disease from developing.

Type 1 diabetes is an autoimmune disorder that develops when a person’s immune system reacts to certain molecules in the pancreas that it would usually ignore.  Previously, scientists had identified four of these molecules, but the fifth one remained unknown for 20 years. Now, these researchers have identified the fifth molecule as Tetraspanin-7. Those with type 1 diabetes have antigens in their blood that are specific to each of these five molecules.

Why Is This Diabetes Research Important?

Doctors use tests that look for antibodies specific to these molecules in order to assess the risk of developing type 1 diabetes; the more antibodies a test detects, the higher the person’s chances are of developing diabetes. Discovering this fifth molecule means that these tests can be even more accurate.

Ultimately, though, this discovery goes beyond detecting a risk for diabetes. Scientists are currently looking for ways stop an immune attack before diabetes develops, and they hope that eventually, by detecting these antibodies and assessing the risk of type 1 diabetes, they can prevent it from ever developing.

Support More Innovative Type 1 Diabetes Research From Early-Career Scientists

Our vision is to eliminate type 1 diabetes by supporting innovative scientific inquiry; it’s why we exist.

To show your support of research projects to help scientists better understand type 1 diabetes and to find a way to treat, cure and prevent the disease, join our list of donors. Whether you support a specific research project or donate to our General Fund, supporting operating costs and funding scientific research, we’re grateful to have you on our team.

Source: http://www.alphagalileo.org/ViewItem.aspx?ItemId=163437&CultureCode=en

Learn More +
Measuring blood sugar

Artificial Pancreas Protocol Deemed Feasible for Younger Kids

Original article published by HealthDay News on May 12, 2016. Click here to read the original article.

Artificial pancreas linked to three-fold reduction of time-in-hypoglycemia for 5- to 9-year-olds

THURSDAY, May 12, 2016 (HealthDay News) — A child-specific version of the modular model predictive control (MMPC) algorithm is feasible and safe for 5- to 9-year-old children with type 1 diabetes, according to the first outpatient single-hormone artificial pancreas (AP) trial in a population of this age, published online May 10 inDiabetes Care.

Simone Del Favero, Ph.D., from the University of Padua in Italy, and colleagues conducted an open-label, randomized, crossover trial involving 30 children, aged 5 to 9 years, with type 1 diabetes. The authors compared three days with an AP with three days of parent-managed sensor-augmented pump (SAP).

The researchers observed a reduction in overnight time-in-hypoglycemia with the AP versus the SAP (median, 0.0 versus 2.2 percent; P = 0.002), with no significant change of time-in-target (56.0 and 59.7 percent, respectively; P = 0.430); there was an increase in mean glucose (173 versus 150 mg/dL; P = 0.002). The AP was associated with a three-fold reduction of time-in-hypoglycemia (P < 0.001) at a cost of reduced time-in-target (P = 0.022) and increased mean glucose (P < 0.001).

“This trial, the first outpatient single-hormone AP trial in a population of this age, shows feasibility and safety of MMPC in young children,” the authors write. “Algorithm retuning will be performed to improve efficacy.”

Several authors disclosed financial ties to pharmaceutical and medical device companies, several of which provided equipment for the study.

Learn More +
Islet transplantation requires immunosuppressive drugs be taken for the rest of a person's life, though improving the body's ability to manage glucose levels significantly lowers the risk for adverse health events. islet transportation Andrey_Popov/Shutterstock

Islet Transplantation May Correct Type 1 Diabetes, Study says

Original article written by Stephen Feller and published by United Press International on April 26, 2016. Click here to read the original article.

WASHINGTON, April 18 (UPI) — Transplants of islet cells, the cells responsible for producing insulin in the pancreas, helped people with type 1 diabetes establish near-normal control of their glucose levels, get free of hypoglycemic events and in many cases no longer need insulin therapy.

Just under 90 percent of patients receiving islet cell transplants in a National Institutes of Health-sponsored clinical trial showed significant improvement in management of their condition during the course of a year, inching researchers closer to a cure for the genetically-caused disease.

Type 1 diabetes is an autoimmune disorder, in which the immune system attacks islet cells, preventing the release of insulin, making it difficult for the body to break down sugars for use, storage or excretion.

The clinical trial, spearheaded by the Clinical Islet Transplantation Consortium, announced in September that the first patient in the study no longer needed insulin therapy.

With results from the rest of the phase 3 trial in hand, the researchers said they will look to license technology to manufacture purified human pancreatic islets for mass use, while also continuing studies on the safety and efficacy with varied groups of patients.

“For people unable to safely control type 1 diabetes, islet transplantation offers real hope for preventing severe, life-threatening hypoglycemia,” Dr. Tom Eggerman, a researcher at the National Institute of Diabetes and Digestive and Kidney Diseases, said in a press release.

For the study, published in the journal Diabetes Care, researchers recruited 48 patients at eight university medical centers around the United States.

All patients received purified islet cells from deceased human donors, with each participant given the transplant into the portal vein, which carries blood from the intestine to the liver. Each of the patients was also given immunosuppressive drugs to prevent their immune systems from rejecting the cells.

After one year, 87.5 percent of participants had no hypoglycemic events, near-normal control of glucose and better awareness of their condition. After one year, 52 percent of patients no longer needed insulin therapy.

Of patients who did not see results within 75 days — they still needed insulin treatments — 25 patients received a second transplant, and one patient received a third.

The researchers worked with the U.S. Food and Drug Administration to run the trialwith future plans for mass manufacture in mind, potentially speeding up the approval process.

“The findings suggest that for people who continue to have life-altering severe hypoglycemia despite optimal medical management, islet transplantation offers a potentially lifesaving treatment that in the majority of cases eliminates severe hypoglycemic events while conferring excellent control of blood sugar,” said Dr.Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

Learn More +
Salk researchers Michael Downes, Ron Evans and Eiji Yoshihara. — Salk Institute

Salk Makes Step Toward Cellular Diabetes Treatment

Original article written by Bradley J. Fikes and published by The San Diego Union-Tribune on April 15, 2016. Click here to read the original article.

Salk Institute scientists say they’ve discovered a key ingredient needed to make functional insulin-producing beta cells. With that knowledge, the scientists say they can realize a dream in treating Type 1 diabetes: growing replacement beta cells from the patients themselves.

If these replacement cells can be implanted and protected, they will make insulin as the body needs, just as the original cells do. That means type 1 diabetes would, for the first time ever, be curable.

The ingredient is a protein called ERR-gamma that turns up energy production in the beta cells, said Ron Evans, a Salk researcher who co-led the study with colleague Michael Downes. These cells are made from artificial embryonic stem cells, called induced pluripotent stem cells. Typically produced from skin, these IPS cells cells are being examined for their potential to treat a variety of diseases.

The study, published Tuesday in the journal Cell Metabolism, provides more evidence that cell replacement therapy may eventually provide a cure for type 1 diabetes, caused by the destruction of beta cells through an autoimmune reaction. The study can be found atj.mp/evansbeta. The first author was Eiji Yoshihara, first author of the paper and a Salk research associate.

Type 2 diabetes is even more common than Type 1. In the United States as of 2012, about 1.25 million children and adults have type 1 diabetes, and 29.1 million had the type 2 form, according to the American Diabetes Association. In San Diego County as of 2012, about 140,600 or 6.2 percent have type 2 diabetes.

In type 2 diabetes, the body becomes resistant to insulin, and the pancreas may become disease and have trouble producing sufficient insulin. As a result, blood sugar rises beyond normal, producing all sorts of damage. This can include weight gain, heart problems, poor limb circulation leading to amputation, kidney disease and blindness. These patients may also come to require insulin.

Disease reversal

Unlike the first kind, type 2 diabetes can be reversed, at least in some cases. Dieting and exercise leading to weight loss is key, according to recent research. A 2013 study in the journal Diabetes Care found that causing patients to burn more substantially more calories than they consume, either by diet or bariatric surgery, restores insulin sensitivity over a period of 8 weeks.

Bariatric surgery, which a portion of the gut is removed to limit food absorption, appears to reverse type 2 diabetes in nearly all patients, according to other studies.

But diets are notoriously hard to adhere to, and bariatric surgery is a drastic step many people are reluctant to take. So scientists are focusing on how type 2 diabetes arises in the first place, with the hope of finding some way of preventing it from taking place at all.

A 2014 study by UCSD researchers led by Dr. Jerrold Olefsky found that a lack of oxygen in fat cells is the trigger that starts the process that ends up causing type 2 diabetes. The study, published in the journal Cell, examined the disease in mouse models, considered a good proxy for human diabetes.

It reported that certain fatty acids, especially saturated fats, increased the need for oxygen in fat cells, causing them to fall into an oxygen-deprived state. This led to inflammation, an immune reaction and insulin resistance.

If the study results are borne out in people, it may be possible to produce a drug that would stop this process in the bud. It won’t stop obesity, but the most drastic health problems would be prevented.

For type 1 diabetes, no treatment exists to reverse the disease.

A very limited form of cell replacement therapy is already used for those with the most dangerous form of type 1 diabetes. They get transplants of islet cells or pancreases from cadavers. Those treated belong to a small subset of type 1 diabetics who get no warning signs that their blood sugar has fallen too far. They can die as a result.

Cell replacement

San Diego’s ViaCyte is already testing a replacement therapy using progenitor cells derived from human embryonic stem cells. In animal testing, these cells mature into beta and other pancreatic “islet” cells.

Another approach with induced pluripotent stem cells is being researched in the lab of Harvard University researcher Douglas Melton. He and colleagues have come up with their own formula for producing beta cells, and published studies outlining the approach.
Melton’s group reports that the cells express genetic activity very similar to adult beta cells, and regulated blood sugar when transplanted into mice whose own beta cells were destroyed.

These therapies all face difficulties, the trickiest perhaps being the patient’s own immune system, which destroyed their own islet cells in the first place.

Islet and pancreatic transplant patients are given immunosuppresive drugs. These drugs are toxic and make the patients more vulnerable to infection. Therefore, these procedures are used only on type 1 diabetics at greatest risk, said Julia L. Greenstein, vice president of discovery research at the research foundation JDRF.

ViaCyte has pioneered another approach to the problem. The islet cells are encapsulated in a semipermeable membrane that keeps out the immune system, but allows nutrients to flow in, and insulin and waste products to flow out. Moreover, the islet cells may potentially produce other blood sugar-relating hormones besides insulin.

Whether that strategy works is the point of clinical testing of ViaCyte’s product, now in a Phase 1 trial. This trial tests for safety. Participants receive easily removable implants of encapsulated cells, which are expected to mature in place and produce insulin. These implants are being removed periodically and examined to make sure the maturation process is going smoothly and that the membrane remains intact.

Presumably, other stem cell-based replacement therapies such as that the Salk scientists or Melton are developing will require an immune system-blocking barrer like ViaCyte’s, to protect the cells. Meanwhile, research continues on ways to modulate the immune system of type 1 diabetes to stop the autoimmune reaction.

Power to the cells

The Salk Institute’s Evans said applying the ERR-gamma protein promotes the growth of mitochondria, the power plants of cells. This gives the cells energy to make insulin.

“It turns on the light, it turns on the energy that flows into the cell. And that we think is the missing link,” Evans said. “It is a switch that controls mitochondrial numbers and activity. You really rev up the power of the cell. Instead of having a weak or indolent cell, you rev it up to the level that it needs to be able to release insulin in response to glucose. And that takes a lot of energy.”

In mouse models, the effect of the therapy is immediate, he said.

“The day that we implant them, the diabetes starts going away,” Evans said. “These cells, you can purify them in a dish. You can grow them exactly the way you want, to hundreds of millions of cells that all share common features. For human therapy, you need that.”

Further research may enable production of different islet cells that make other important hormones to regulate blood sugar, Evans said. And a few more years of testing and preclinical development, it should be possible to test the therapy in humans.

Learn More +

Beta Cells From Love Handles

Original article written by Eth Zurich and published by EurekAlert! American Association for the Advancement of Science (AAAS) on April 11, 2016. Click here to read the original article.

Researchers led by Martin Fussenegger, Professor of Biotechnology and Bioengineering at ETH Zurich’s Department of Biosystems Science and Engineering in Basel, have performed a feat that many specialists had until now held to be impossible: they have extracted stem cells from a 50-year-old test subject’s fatty tissue and applied genetic reprogramming to make them mature into functional beta cells.

In the presence of glucose, the beta cells generated using this “genetic software” produce the hormone insulin – just like natural beta cells, which are found in the pancreas. The researchers reported this in the journal Nature Communications.

112856_web
The diagram shows the dynamics of the most important growth factors during differentiation of human induced pluripotent stem cell to beta-like cells. CREDIT: Eth Zurich

Maturation dynamic reproduced

The Basel-based researchers took the stem cells and added a highly complex synthetic network of genes – the genetic software. They designed this network to precisely recreate the key growth factors involved in this maturation process.

Central to the process are the growth factors Ngn3, Pdx1 and MafA. Concentrations of these factors change during the differentiation process. For instance, MafA is not present at the start of maturation. Only on day four, in the final maturation step, does it appear, its concentration rising steeply and then remaining at a high level. The changes in concentration of Ngn3 and Pdx1, however, are very complex: while the concentration of Ngn3 rises and then falls again, the level of Pdx1 rises at the beginning and towards the end of maturation.

Fussenegger stresses that it is essential to reproduce these natural processes as closely as possible in order to produce functioning beta cells: “The timing and the quantities of these growth factors are extremely important.”

New beta cells respond to glucose

In Fussenegger’s opinion, it is a real breakthrough that a synthetic gene network has been successfully used to achieve genetic reprogramming that delivers beta cells. Until now, scientists have controlled such stem cell differentiation processes by adding various chemicals and proteins using pipettes.

“It’s not only really hard to add just the right quantities of these components at just the right time, it’s also inefficient and impossible to scale up,” Fussenegger says. In contrast, the new process can successfully transform three out of four adipose stem cells into beta cells.

These beta cells not only look very similar to their natural counterparts – both kinds contain dark spots known as granules, which store insulin. The artificial beta cells also function in a very similar way. “At the present time, the quantities of insulin they secrete are not as great as with natural beta cells,” he admits.

But the key point is that the researchers have for the first time succeeded in reproducing the entire natural process chain, from stem cell to differentiated beta cell.

Implants of endogenous cells

In future, the Basel-based ETH researchers’ new technique might make it possible to implant new functional beta cells in diabetes sufferers that are made from their own adipose tissue.

While beta cells have been transplanted in the past, this has always required subsequent suppression of the recipient’s immune system – as with any transplant of donor organs or tissue. “With our beta cells, there would likely be no need for this action, since we can make them using endogenous cell material taken from the patient’s own body,” Fussenegger says, adding: “This is why our work is of such interest in the treatment of diabetes.”

Complete maturation in the petri dish

To date, the ETH researchers have merely cultured their beta cells; they have yet to implant them in a diabetes sufferer. This is because they first wanted to test whether stem cells could be fully differentiated from start to finish using genetic programming.

Fussenegger is convinced that this new method could also be used to produce other cells. Stem cells taken from adipose tissue could be differentiated into various cell types, he says – “And most people have an overabundance of fat from which these stem cells can be harvested.”

###

Saxena P, Heng BC, Bai P, Folcher M, Zulewski H, Fussenegger, M. A programmable synthetic lineage-control network that differentiates human IPSCs into glucose-sensitive insulin-secreting beta-like cells. Nature Communications, published online April 11th 2016. DOI: 10.1038/NCOMMS11247

 

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Learn More +
Diabetes Supplies - Bottles

Consequences and Burdens of Type 1 Diabetes in Low-Income and Middle-Income Countries

Diabetes is a global epidemic. Just consider the following from the World Health Organization’s fact sheet on diabetes:

-In 2014 the global prevalence of diabetes was estimated to be 9% among adults aged 18+ years
-In 2012, an estimated 1.5 million deaths were directly caused by diabetes
-More than 80% of diabetes deaths occur in low- and middle-income countries
-WHO projects that diabetes will be the 7th leading cause of death in 2030

Most everyone in the U.S. has likely felt the burden of diabetes in one way or the other, but in low and middle income, the burden of diabetes is felt even more strongly, as poor access to health services is coupled with a lack of primary health care education.

A Lack of Money to Treat Diabetes

Though insulin was discovered 95 years ago, children and young people across the world still suffer or die from preventable complications because of a lack of insulin. This is due to limited access to insulin globally, particularly in many parts of the developing world. What’s more, even when insulin is available, many families struggle with the cost of insulin and test strips because the cost is so disproportionate to their average monthly income. As of 2012, 12.7% of people across the world live on less than $2 a day. With an income this limited, many of those afflicted with type 1 diabetes simply can’t afford the medicine they need every day. With around 78,000 children under 15 being diagnosed with type 1 diabetes each year, the demand for insulin is only increasing.

A Lack of Type 1 Diabetes Education

In addition to poor access to medical supplies in low-income and middle-income countries, education on living with diabetes is severely lacking in developing countries. Without adequate diabetes education and support, living a full, productive and healthy life with diabetes can be nearly impossible. Even with access to insulin, not knowing how to properly manage your diabetes has severe health repercussions.
What’s more, myths about diabetes abound in many developing nations. A study in India, which has the largest number of patients with diabetes and is known as the “Diabetes capital of the world,” found that nearly half of adult patients surveyed believed that diabetes can be cured by herbal treatment and that bitter foods reduce the elevated blood sugar levels. Misconceptions and myths such as these result from insufficient education and awareness about type 1 diabetes, and only serve to increase the economic and public health burdens of diabetes in low-income and middle-income countries.

The Cyclical Challenges of Diabetes

To make matters worse, the problems of diabetes globally aren’t solely a lack of medication and healthcare. Rather, it becomes cyclical, creating a challenge to not just thrive, but survive.

Consider the child who has diabetes but has inadequate access to insulin and test strips, leading to recurring bouts of diabetic ketoacidosis. Because of this, he can’t attend school regularly. By the time he reaches adulthood, his education is severely lacking. This affects his ability to get a job that pays enough to cover the cost of supplies to manage his diabetes in adulthood. In addition to not being able to afford the medical supplies he needs, his lower level of education means that he’s statistically more likely to believe common myths and misconceptions regarding diabetes, making it even harder to manage.

Ultimately, living with diabetes presents unique challenges no matter where you live, but living with type 1 diabetes in low-income and middle-income countries can significantly exacerbate these challenges. This is why the Diabetes Research Connection has made it our mission to support innovative scientific inquiry until diabetes is eliminated across the globe.

To get involved in the global fight against type 1 diabetes, support one of our diabetes research projects.

Learn More +
Type 1 Diabetes Researchers

How to Get Involved in the Global Fight Against Diabetes

The Diabetes Research Connection’s mission is to connect donors with early-career scientists, enabling them to perform peer-reviewed, novel research designed to prevent and cure type 1 diabetes, minimize its complications and improve the quality of life for those living with the disease.

April 7 is World Health Day 2016, and this year’s theme is “beat diabetes”. In recognition of this, we invite you to join us in the global fight against diabetes. Read on to learn about a few ways you can get involved.

Support early-career scientists’ research.

We’ve made it easy for donors and strong proponents of type 1 diabetes research to help fund young scientists with exciting and inventive research project ideas. Currently, we’re raising money to fund two projects. Joseph Lancman, Ph.D., of Sanford Burnham Prebys Medical Discovery Institute, is researching ways to replace insulin producing beta-cells, allowing recipients to live a life free of daily insulin injections, while Sangeeta Dhawan, Ph.D., of UCLA’s School of Medicine, is researching how to create better insulin producing cells with cell regeneration. When you support one or more of these projects, 100% of your contribution goes directly to the scientists.

Submit research project ideas or refer early-career scientists to the Diabetes Research Connection.

Have an innovative idea for a type 1 diabetes research project? We can help you get it funded by facilitating the connection between donors and scientists.

Graduate students, post-docs, instructors and nontenured junior faculty whose work is focused on type 1 diabetes are invited to apply. Grants are up to $50,000 for one year, and scientists receive 100% of what they raise.

Serve on a peer-review committee.

If you’d like to get more deeply involved in the fight to beat type 1 diabetes, consider serving on one of our committees. Our Scientific Review Committee consists of more than 80 diabetes experts from across the country who volunteer their time and expertise to vet each research project we work with for novelty and scientific merit. Our Layperson Review Committees help scientists translate complex and jargon-heavy descriptions into simple and engaging website presentations that donors are likely to fund.

Learn more about serving on a committee here.

Engage online with social media.

Help raise awareness of the research currently being done to cure type 1 diabetes by joining us online. Follow us on Facebook, Twitter, LinkedIn and Instagram, and help us reach even more people by liking and sharing our posts.

Learn More +
iLet

The Bionic Pancreas Is Getting Closer To Reality

Original article published in TIME HEALTH by Alexandra Sifferlin on April 1, 2016. To view the original article Click Here.

The invention could seriously change the management of type-1 diabetes

The race is on for what may be the biggest innovation in decades for Type 1 diabetes management—the bionic pancreas—and on Friday, one of the lead researchers in the field announced at the Endocrine Society’s annual meeting that he’s launched a company to bring that invention to market.

unknown1Ed Damiano, a professor of biomedical engineering at Boston University who is developing a bionic pancreas (also referred to as the artificial pancreas), has spun his academic research into a company called Beta Bionics. Recently, Beta Bionics secured $5 million from the pharmaceutical company Eli Lilly, which manufactures the insulin used in the device. “My goal is to bring this technology in a responsible and expeditious manner to as many people with diabetes as possible,” says Damiano.

As TIME previously reported, Damiano was inspired to make the device when his son David was diagnosed with diabetes as an infant. He wants the device on the market by the time David, now 16, goes off to college.

People with diabetes are constantly tracking and adjusting their blood sugar with insulin or food. A bionic pancreas would automate that process. Damiano’s device, called the iLet, takes blood sugar readings every five minutes, and depending on blood-sugar levels, releases insulin to bring the sugar down or another hormone called glucagon to bring it back up, keeping blood sugar steady throughout the day.

Damiano incorporated Beta Bionics as a benefit corporation. A benefit corporation allows companies to have a protected public-benefit mission. “It’s a for-profit organization but you are allowed to make management decisions that are in the interest of your mission that may or may not maximize return of equity to shareholders,” explains Damiano.

Beta Bionics is not without competition. Other research groups are developing similar technology. The medical device company Medtronic is in the game, and researchers at the University of Virginia and Harvard University announced in January that they will soon test their artificial pancreas in 240 people. One of the differences between Beta Bionic’s device and others is that instead of offering automated insulin delivery only, Beta Bionic’s also releases glucagon, which allows people to bring up their blood sugar without eating a snack. Damiano says they will likely have an insulin only version of the iLet approved in 2018 with the full system approved soon after that. Beta Bionics plans to begin its final pivotal clinical trial of the device in the middle of 2017.

I’m still very hopeful about the bionic pancreas and we’re getting closer,” says Fred Cunha, whose daughter Elise, 8, was one of the youngest people to try the bionic pancreas in a trial.Even though my wife and I can see her blood sugar on our Apple watches these days, it’s still a twenty-four-seven deal.”

Learn More +

KUSI News anchor Brad Perry interviews Duc Dong, Ph.D. and Joseph Lancman, Ph.D

KUSI News anchor Brad Perry interviews Duc Dong, Ph.D. and Joseph Lancman, Ph.D of Sanford Burnham Prebys Medical Discovery Institute in La Jolla on ground breaking research regarding type 1 diabetes. Click here to learn more about the project and help support their research today: Replacement Beta-Cells From An Unexpected Source.

Learn More +

Scientists Create Painless Patch Of Insulin-Producing Beta Cells To Control Diabetes

Original article published by EurekAlert! American Association for the Advancement of Science (AAAS) on March 14, 2016. Click here to read the original article.

This new ‘smart cell patch’ developed at UNC and NC State is a proof of principle to treat millions of people with type-1 and advanced type-2 diabetes

UNIVERSITY OF NORTH CAROLINA HEALTH CARE

111053_web
THIS IS A SCANNING ELECTRON MICROSCOPIC (SEM) IMAGE OF THE MICRONEEDLE-ARRAY PATCH DEVELOPED IN THE LAB OF ZHEN GU, PH.D.

CHAPEL HILL, NC – For decades, researchers have tried to duplicate the function of beta cells, the tiny insulin-producing entities that don’t work properly in patients with diabetes. Insulin injections provide painful and often imperfect substitutes. Transplants of normal beta cells carry the risk of rejection or side effects from immunosuppressive therapies.

Now, researchers at the University of North Carolina at Chapel Hill and North Carolina State University have devised another option: a synthetic patch filled with natural beta cells that can secrete doses of insulin to control blood sugar levels on demand with no risk of inducing hypoglycemia.

The proof-of-concept builds on an innovative technology, the “smart insulin patch,” reported last year in the Proceedings of the National Academy of Sciences. Both patches are thin polymeric squares about the size of a quarter and covered in tiny needles, like a miniature bed of nails. But whereas the former approach filled these needles with manmade bubbles of insulin, this new “smart cell patch” integrates the needles with live beta cells.

Tests of this painless patch in small animal models of type-1 diabetes demonstrated that it could quickly respond to skyrocketing blood sugar levels and significantly lower them for 10 hours at a time. The results were published in Advanced Materials.

“This study provides a potential solution for the tough problem of rejection, which has long plagued studies on pancreatic cell transplants for diabetes,” said senior author Zhen Gu, PhD, assistant professor in the joint UNC/NC State department of biomedical engineering. “Plus it demonstrates that we can build a bridge between the physiological signals within the body and these therapeutic cells outside the body to keep glucose levels under control.”

Beta cells typically reside in the pancreas, where they act as the body’s natural insulin-producing factories. In healthy people, they produce, store, and release the hormone insulin to help process sugar that builds up in the bloodstream after a meal. But in people with diabetes, these cells are either damaged or unable to produce enough insulin to keep blood sugar levels under control.

Diabetes affects more than 387 million people worldwide, and that number is expected to grow to 500 million by the year 2030. Patients with type-1 and advanced type-2 diabetes must regularly monitor their blood sugar levels and inject themselves with varying amounts of insulin, a process that is painful and imprecise. Injecting the wrong amount of medication can lead to significant complications like blindness and limb amputations, or even more disastrous consequences such as diabetic comas and death.

Since the 1970s, researchers have researched transplantation of insulin-producing cells as an alternative treatment for diabetes. The first successful transplant of human beta cells was performed in 1990, and since then hundreds of diabetic patients have undergone the procedure. Yet, only a fraction of treated patients achieved normal blood sugar levels. Most transplants are rejected, and many of the medications used to suppress the immune system wind up interfering with the activity of beta cells and insulin. More recently, researchers have been experimenting with ways to encapsulate beta cells into biocompatible polymeric cells that could be implanted in the body.

Gu, who also holds appointments in the UNC School of Medicine, the UNC Eshelman School of Pharmacy, and the UNC Diabetes Care Center, decided to create a device that would put the blood-sugar buffering properties of beta cells out of reach of the patient’s immune system. Lead author Yanqi Ye, a graduate student in Gu’s lab, constructed the “smart cell patches” using natural materials commonly found in cosmetics and diagnostics. She stuffed the hundreds of microneedles, each about the size of an eyelash, with culture media and thousands of beta cells that were encapsulated into microcapsules made from biocompatible alginate. When applied to the skin, the patch’s microneedles poked into the capillaries and blood vessels, forming a connection between the internal environment and the external cells of the patch.

Ye also created “glucose-signal amplifiers,” which are synthetic nanovesicles filled with three chemicals to make sure the beta cells could “hear” the call from rising blood sugar levels and respond accordingly.

Gu’s group showed that blood sugar levels in diabetic mice quickly declined to normal levels. To assess whether the patch could regulate blood sugar without lowering it too much, the researchers administered a second patch to the mice. As they had hoped, repeated administration of the patch did not result in excess doses of insulin, and thus did not risk hypoglycemia. Instead, the second patch extended the life of the treatment to 20 hours.

Further modifications, pre-clinical tests, and eventually clinical trials in humans will all be necessary before the patch can become a viable option for patients. But for now, the researchers believe their results provide a proof of principle for an alternative approach that could be safer and less cumbersome than current treatments.

“Managing diabetes is tough for patients because they have to think about it 24 hours a day, seven days a week, for the rest of their lives,” said co-author John Buse, MD, PhD, professor of medicine at the UNC School of Medicine and director of the UNC Diabetes Care Center and the NC Translational and Clinical Sciences Institute. “These smart insulin approaches are exciting because they hold the promise of giving patients some time off with regards to their diabetes self-care. It would not be a cure but a desperately needed vacation.”

###

The research was funded by grants from NC TraCS, home of the NIH Clinical and Translational Science Award at UNC, the American Diabetes Association, and the National Science Foundation through the ASSIST Engineering Center at NC State.

Study co-authors from UNC were Jicheng Yu, Chao Wang, Nhu-Y Nguyen, and Glenn M. Walker.

 

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Learn More +

The Next Step in Preventing Diabetes

Original article written by German Research For Environmental Health on March 15, 2016. Click here to read the original article.

Neuherberg, March 15, 2016. A team of scientists at Helmholtz Zentrum München, in collaboration with Technische Universität München and the German Center for Diabetes Research (DZD), have shown in a preclinical model that specifically modified insulin mimetopes may lead to an immune tolerance. The results, published in ‘Nature Communications’, may be a step to improved prevention of type 1 diabetes.

csm_Daniel_Serr_01_6511cfd60b
Dr. Carolin Daniel (left), Isabelle Serr

Type 1 diabetes affects 30,000 individuals throughout Germany and is the most common metabolic disease in children and adolescents. To halt the ever-increasing incidence, the young investigator group “Immunological Tolerance in Type 1 Diabetes” at the Institute of Diabetes Research directed by Prof. Dr. Anette-Gabriele Ziegler is exploring new strategies to prevent the onset of the disease.

In the current study, the scientists investigated the effect of specifically modified insulin mimetopes on the immune system.* “In particular, we wanted to find out whether we can induce the protective regulatory T cells to produce a tolerance of the body against insulin, if we bring them into contact with our novel peptides,” said Dr. Carolin Daniel, who leads a young investigator group and directs the study.

Tregs_72dpi
Optimized mimetopes increase the number of regulatory T cells (transcription factor Foxp3 in red) in the vicinity of the insulin producing beta cells of the pancreas (insulin in green). / Source: Helmholtz Zentrum München

Optimized mimetopes curb the immune system

The study is based on findings Daniel made several years ago at Dana Farber Cancer Institute and Harvard Medical School in Boston. There she showed that insulin mimetopes she optimized were significantly more efficient in inducing a tolerance through regulatory T cells towards insulin than their natural counterparts (epitopes). In young mice, the induction of insulin mimetopes at low doses completely halted the development of type 1 diabetes.

The next step was achieved in the study that has just been published: In a so-called humanized mouse model, whose immune system is very similar to that of humans, the scientists were able to confirm the results** – an important indication for the effectiveness of the optimized human insulin mimetopes.“In fact, we were able to show that the new vaccine efficiently stimulates the regulatory T cells, which then can impede the attack of the immune system on the insulin-producing cells,” said lead author Isabelle Serr, who was involved in the study within the framework of her dissertation.

In the long term Daniel and her group want to further develop the method for preventive treatment of children at high risk for type 1 diabetes. “An important step will be to test the new therapy clinically – that is our vision“, said Daniel with regard to the future.

Further Information

Background:
* In patients with type 1 diabetes, the insulin-producing cells in the islets of Langerhans of the pancreas are destroyed because they are attacked by the body’s own immune system (formation of islet autoantibodies against structures of beta cells). As a result, the pancreas can no longer supply the body with sufficient insulin. If the destruction of the beta cells exceeds a certain extent, the disease breaks out and blood glucose levels rise due to the lack of insulin. Source: www.Diabetesinformationsdienst-Muenchen.de** The investigation of complex biological processes requires in vivo studies. Here the mouse is a preferred experimental model. Unfortunately, the transferability of such experiments to the human organism is not always given. Therefore, models in which human cells or tissue can be studied in an animal are becoming increasingly important. The “humanized mouse” represents an especially attractive translation model for studying diseases of the immune system. The benefits of such a model, however, depend on the ability to accurately mimic the human immune system. For this purpose, mouse models are used such as the HLA-DQ8 NOD/scid-IL2rgnull mouse model, which lacks an own murine immune system. These mouse models, for example, are reconstituted with human hematopoietic stem cells and subsequently enable successful engraftment and the development of a human immune system to study relevant processes in vivo.

 

Original publication::
Serr, I. et al. (2016). Type 1 diabetes vaccine candidates promote human Foxp3+Treg induction in humanized mice, Nature Communications, DOI: 10.1038/ncomms10991
Link: http://www.nature.com/ncomms/2016/160315/ncomms10991/full/ncomms10991.html

As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,300 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. www.helmholtz-muenchen.de/en/index.html

Technical University of Munich (TUM) is one of Europe’s leading research universities, with more than 500 professors, around 10,000 academic and non-academic staff, and 39,000 students. Its focus areas are the engineering sciences, natural sciences, life sciences and medicine, reinforced by schools of management and education. TUM acts as an entrepreneurial university that promotes talents and creates value for society. In that it profits from having strong partners in science and industry. It is represented worldwide with a campus in Singapore as well as offices in Beijing, Brussels, Cairo, Mumbai, San Francisco, and São Paulo. Nobel Prize winners and inventors such as Rudolf Diesel, Carl von Linde, and Rudolf Mößbauer have done research at TUM. In 2006 and 2012 it won recognition as a German “Excellence University.” In international rankings, TUM regularly places among the best universities in Germany. www.tum.de/en/homepage

The Institute of Diabetes Research (IDF) focuses on the pathogenesis and prevention of type 1 diabetes and type 2 diabetes as a long-term effect of gestational diabetes. A top-priority project is the development of an insulin vaccination against type 1 diabetes. In large-scale, long-term studies the IDF examines the implication of genes, environmental factors and the immune system in the pathogenesis of type 1 diabetes. Using data from the BABYDIAB cohort, which was established in 1989 as the world’s first prospective diabetes birth cohort, risk genes and antibody profiles can both be identified. This allows predictions about the development and onset of type 1 diabetes and will change the classification and the time of diagnosis. The IDF is part of the Helmholtz Diabetes Center (HDC). www.helmholtz-muenchen.de/en/idf/index.html

The German Center for Diabetes Research  (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Zentrum München – German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich. www.dzd-ev.de/en/index.html

Scientific contact:
Dr. Carolin Daniel, German Research Center for Environmental Health (GmbH), Institute of Diabetes Research, young investigator group „Immunological Tolerance in Type 1 Diabetes“, Ingolstädter Landstr. 1, 85764 Neuherberg – Tel. +49 89 3187 2188 – carolin.daniel@helmholtz-muenchen.de

 

 

Learn More +
Diabetes Research Connection Logo

Simplified Autologous Hematopoietic Stem Cell Transplantation Shows Promise In Type 1 Diabetes

Original article written by Cantú-Rodríguez OG, et al. J Clin Endocrinol Metab. 2016;doi:10.1210/jc.2015-2776 on February 23, 2016. Click here to read the original article.

In patients with type 1 diabetes, simplified autologous hematopoietic stem cell transplantation in an outpatient setting appears to be a safe and effective intervention, according to study data.

Fernando Lavalle­González, MD, an endocrinologist at the Universidad Autónoma de Nuevo León in Mexico, and colleagues evaluated 16 children (median age, 12 years) with type 1 diabetes to determine the effect of simplified autologous hematopoietic stem cell transplantation in the outpatient setting on long-­term insulin independence, changes in HbA1c and the safety of the procedure. The median follow­-up was 34 months.

All patients underwent the procedure on a 100% outpatient basis without severe complications, and there was no mortality at 100 days of follow­-up.

The overall response was 81%, with a reduction in overall daily insulin requirements from 0.41 U/kg to 0.32 U/kg by the third month (P = .46). Insulin dependence was achieved by seven participants (44%); five were insulin­-independent by the third month and one attained freedom from insulin within the first week after transplantation. Two participants who achieved partial insulin independence at 6 months post-procedure achieved complete insulin independence at 11 months and 1 year post-transplant. Three patients were deemed non-responders, and the remaining six showed partial insulin independence. In all groups, HbA1c levels demonstrated a total mean decrease of 0.87% during the 3 months of study, a 1% decrease at 6 months and 1.6% decrease at the last follow-­up. At 6 months, the insulin­-independent group exhibited a mean HbA1c reduction of –2.3%.

“The transplant was fully accomplished on an outpatient basis, thereby reducing costs, limiting exposure to nosocomial infections and avoiding the inconvenience of hospitalization,” the researchers wrote. “This method should be further studied in a larger cohort including an appropriate contemporary control group as it appears to be capable of changing the natural history of type 1 diabetes mellitus.” – by Jennifer Byrne

Disclosure: The researchers report no relevant financial disclosures.

Learn More +

Reprogrammed Stomach Tissue As A Renewable Source Of Functional β Cells For Blood Glucose Regulation

Original article published in Cell Stem Cell on February 18, 2016. Click here to read the original article.

Graphical Abstract:
Graphical abstract V1Authors: Chaiyaboot Ariyachet, Alessio Tovaglieri, Guanjue Xiang, Jiaqi Lu, Manasvi S. Shah, Camilla A. Richmond, Catia Verbeke, Douglas A. Melton, Ben Z. Stanger, David Mooney, Ramesh A. Shivdasani, Shaun Mahony, Qing Xia, David T. Breault, Qiao Zhou

Correspondance: qiao_zhou@harvard.edu

In Brief: Ariyachet et al. show that the antral stomach region of the gastrointestinal tract is particularly amenable to being reprogrammed to a β cell fate because of transcriptional similarity and that bioengineered stomach mini-organs containing reprogrammed cells can rescue hyperglycemia when transplanted into diabetic mice.

 

Highlights

  • Antral stomach cells reprogram effectively to insulin+
    pancreatic β-like cells
  • Antral endocrine cells are transcriptionally related to
    pancreatic β cells
  • Induced insulin+ cells reverse hypoglycemia after
    transplantation in diabetic mice
  • Reprogrammed cells in bioengineered mini-organs give
    functional rescue in vivo

Summary

The gastrointestinal (GI) epithelium is a highly regenerative tissue with the potential to provide a renewable source of insulin+ cells after undergoing cellular reprogramming. Here, we show that cells of the antral stomach have a previously unappreciated propensity for conversion into functional insulin-secreting cells. Native antral endocrine cells share a surprising degree of transcriptional similarity with pancreatic β cells, and expression of β cell reprogramming factors in vivo converts antral cells efficiently into insulin+ cells with close molecular and functional similarity to β cells. Induced GI insulin+ cells can suppress hyperglycemia in a diabetic mouse model for at least 6 months and regenerate rapidly after ablation. Reprogramming of antral stomach cells assembled into bioengineered mini-organs in vitro yielded transplantable units that also suppressed hyperglycemia in diabetic mice, highlighting the potential for development of engineered stomach tissues as a renewable source of functional β cells for glycemic control.

 

Introduction

Major progress has been made in recent years to produce functional insulin+ cells for cell replacement therapies to treat diabetes. These regenerative technologies include directed differentiation of embryonic stem cells and direct conversion from non-β cells such as liver cells, acinar cells, and others (Hebrok, 2012, Johannesson et al., 2015, Nostro and Keller, 2012, Schiesser and Wells, 2014, Zhou and Melton, 2008). However, because ongoing pathological conditions in diabetes inflict continued damage to native and transplanted β cells (Azzi et al., 2010, Butler et al., 2003, Lakey et al., 2006, Rahier et al., 2008), it is desirable to develop a regenerative system where β cells can be produced in a renewable fashion to counteract β cell loss. The gastrointestinal (GI) tissues are potential sources for such continued generation of β cells. The stomach and intestine are unique among endodermal organs in that they harbor large numbers of adult stem/progenitor cells that constantly produce epithelial cells, including hormone-secreting enteroendocrine cells (Barker et al., 2007, Barker et al., 2010, May and Kaestner, 2010, Schonhoff et al., 2004a). Both organs are developmentally related to the pancreas, arising in adjacent embryonic domains (Offield et al., 1996). Development of gut enteroendocrine and pancreatic endocrine cells also depends on common critical factors, such as Ngn3 (also known as Neurog3) (Gu et al., 2002, Jenny et al., 2002, Lee et al., 2002). Recent studies showed that intestinal cells could be converted into insulin+ cells with either endocrine-specific deletion of FoxO1 or ubiquitous expression of NPM reprogramming factors (Ngn3, Pdx1, and Mafa) (Bouchi et al., 2014, Chen et al., 2014, Talchai et al., 2012a). Although these studies revealed the feasibility of deriving β-like cells from the intestine, critical barriers remain in developing these approaches into future regenerative therapies. FoxO1 plays a critical role in protecting β cells from cellular stress (Kitamura et al., 2005, Talchai et al., 2012b), and deletion or suppression of FoxO1 in pancreatic β cells could result in β cell failure (Talchai et al., 2012b, Talchai and Accili, 2015). Moreover, although NPM factors induce insulin+ cells in the intestine, the induced cells appear to lack certain important β cell genes such as Nkx6.1 and exhibit reduced glucose responsiveness compared with pancreatic β cells (Chen et al., 2014).

We sought to devise improved strategies to derive functional insulin-secreting (insulin+) cells from GI tissues and to harness the regenerative capacity of these tissues as a renewable source of β cells. We report the surprising finding that NPM factors reprogram enteroendocrine cells from the antral stomach more efficiently into functional insulin+ cells compared with enteroendocrine cells from the intestine. Induced antral insulin+ cells also express key β cell factors, including Nkx6.1 and Prohormone convertase 2 (PC2), which intestinal insulin+ cells lack. Our data reveal that native antral enteroendocrine cells share a surprising level of transcriptional similarity with pancreatic β cells. Further, the intestine-specific Cdx2 gene can block efficient β cell reprogramming. Thus, intrinsic molecular differences between antral stomach and intestinal enteroendocrine cells could contribute to the differential reprogramming outcomes. To explore the therapeutic potential of gastric tissue as a source of inducible β cells, we created bioengineered stomach mini-organs; upon transplantation and sphere formation, these structures produced renewable insulin+ cells that reverse hyperglycemia in vivo. Our studies reveal antral stomach tissue as a previously unrecognized source that is highly amenable to reprogramming toward functional insulin+ cells. We also provide proof of principle evidence that bioengineered gastric tissue could serve as a renewable source of β cells for glycemic control.

Results

NPM Factors Efficiently Reprogram GI Enteroendocrine Cells to Insulin+ Cells, with Antral Stomach Showing the Highest Induction Efficiency

Previous studies of reprogramming GI tissues to insulin+ cells have used either deletion of FoxO1 or expression of NPM factors (Ngn3, Pdx1, and Mafa). Surprisingly, no insulin+ cells were reported from stomach with either approach (Chen et al., 2014, Talchai et al., 2012a). To revisit this important question, we performed additional reprogramming experiments in the GI tract. Using adenoviral infection of cultured mouse antral stomach organoids, we observed that the NPM factors are highly effective at inducing insulin expression whereas the other reprogramming factors tested, including Pax4, Insm1, Nkx6.1, and Mafa, are not effective (Figure S1). Based on this observation, we constructed new transgenic mouse lines (TetO-NPMcherry) in which the inducible TetO promoter drives polycistronic expression of NPM factors and the red fluorescent protein Cherry (Figure 1A). Global expression of NPM factors leads to rapid animal death due to hypoglycemia (unpublished observations). To enable long-term observation and comparison of induced insulin+ cells from different GI regions, we targeted NPM factors to the GI enteroendocrine lineage, which shares molecular and developmental similarity with pancreatic endocrine cells (Habib et al., 2012, May and Kaestner, 2010, Schonhoff et al., 2004a), making it an excellent target for β cell conversion. We crossed the TetO-NPMcherry line with the bacterial artificial chromosome (BAC)-transgenic Ngn3-Cre line (Schonhoff et al., 2004b) and the knockin Rosa-floxed-rtTA line (Jackson Laboratory) to derive a triple-transgenic line we call NRT (Figure 1A). The well-described Ngn3-Cre line labels all enteroendocrine cells in the intestine and the majority of antral stomach enteroendocrine cells (Schonhoff et al., 2004b) (Figure S1).

Screen Shot 2016-02-19 at 12.30.54 PM

Figure 1

NPM Factors Efficiently Reprogram Gastrointestinal Endocrine Cells to Insulin+ Cells with the Highest Induction Efficiency in Antral Stomach

(A) Diagram of the triple-cross transgenic mouse line, referred to as NRT (Ngn3-Cre; Rosa-floxed-rtTA; Teto-NMPcherry). Ngn3-cre is used to target inducible expression of the NPM factors (Ngn3, Pdx1, and Mafa) into the enteroendocrine cells of the antral stomach and the intestine. Black bars in Teto-NPMcherry indicate 2A peptides used to mediate polycistronic expression.

(B–G) Doxycycline treatment of NRT animals yielded many insulin+cherry+ cells from the antral stomach (B), the duodenum (C), and the colon (D), among other GI regions. Quantitation showed a higher induction efficiency of insulin+ cells in antrum compared with duodenum (du), ileum (IL), and colon (Co) (E, n = 3 animals, p = 0.0026). Antrum tissue also has higher insulin content (F, n = 3 animals, p = 0.0046). Using FACS-purified cherry+ cells, the expression level of transgenes in the endocrine population was found to be comparable (G), n = 3 animals). Scale bar, 100 μm. Yellow arrows indicate insulin+cherry+ cells; white arrowheads indicate insulincherry+ cells.

See also Figure S1.

After doxycycline (Dox) treatment of NRT animals for 10 days, we observed numerous insulin+ cells in the antral stomach and along the entire length of the intestine (Figures 1B–1D, yellow arrows). The fundus region of the stomach contains relatively few Ngn3+ endocrine cells, and very few of these expressed insulin, suggesting that fundal cells resist NPM-mediated conversion (Figure S1). Quantitative analysis showed significantly higher reprogramming efficiency in the antrum (41.5% ± 8.5%, mean ± SD) than in the proximal (duodenum, 21.4% ± 6.7%), middle (ileum, 14.6% ± 3.3%), or distal (colon, 15.5% ± 3.4%) intestine (Figure 1E). The antral stomach also contains substantially higher levels of insulin protein compared with the intestine (Figure 1F), even though levels of reprogramming factor expression in fluorescence-activated cell sorting (FACS)-purified cherry+ cells from the antrum and different intestinal regions are comparable (Figure 1G).

Enteroendocrine cells in the stomach and intestine include multiple subtypes based on hormone expression (Habib et al., 2012, May and Kaestner, 2010, Schonhoff et al., 2004a). To evaluate whether insulin+ cells are preferentially induced in certain subtypes, we quantified seven major enteroendocrine subtypes before and after induction of insulin+ cells (Figure S1). All endocrine subtypes we examined were reduced upon doxycycline treatment, with the exception of serotonin+ cells, which do not originate from the Ngn3+ lineage (Schonhoff et al., 2004b) (Figure S1). These data indicate that insulin+ cells in both stomach and duodenum arise from multiple endocrine subtypes and/or their common progenitors. We also found the vast majority of induced GI insulin+ cells to be mono-hormonal (Figure S1). These data collectively show that NPM factors can robustly reprogram GI endocrine cells into insulin+ cells, with the highest reprogramming efficiency in the antral stomach.

Induced GI Insulin+ Cells Can Reverse Hyperglycemia Long-Term and Regenerate Rapidly upon Ablation

To test whether the induced GI insulin+ cells can secrete insulin and reverse hyperglycemia, we ablated pancreatic β cells in NRT mice with streptozotocin (STZ), which renders the animals hyperglycemic. Upon Dox treatment and induction of insulin+ cells in the GI tract, hyperglycemia was rapidly reversed and blood glucose levels remained normal for as long as we tracked them (Figure 2A, up to 6 months). In contrast to control animals, which died with hyperglycemia within 8 weeks, nearly every Dox-treated animal was rescued (Figure 2B). Consistent with this effect, intraperitoneal glucose tolerance test (IPGTT) showed substantial improvement after doxycycline induction (Figure 2C) and near-normal blood insulin level in STZ-ablated and Dox-induced animals (Figure 2D).

Fig2 QZ

Figure 2

Induced Insulin+ Cells from the GI Tract Can Reverse Hyperglycemia Long-Term and Regenerate Rapidly

(A) Glucose monitoring of hyperglycemic NRT animals over 6 months. Streptozotocin (STZ) was used to ablate endogenous pancreatic β cells and create hyperglycemia. Doxycycline (Dox) was administered continuously from week 1 onward (red line). Compared with persistent hyperglycemia and death of control animals (−Dox group, black squares), Dox treatment led to long-term suppression of hyperglycemia (+Dox group, red circles). A second round of STZ ablation was conducted at week 10 to evaluate the regenerative capacity of this experimental system. The ensuing hyperglycemia was suppressed again by week 13. Pancreatectomy was performed on week 19 to remove ∼80% of the pancreas. No significant effect on blood glucose levels was observed.

(B–D) Dox treatment and induction of insulin+ cells led to significant improvement in the survival of hyperglycemic NRT animals (B, n = 12 animals in each group). Glucose tolerance tests showed near-normal responses for Dox-treated animals (C, n = 4 animals in each group). The blood insulin levels of the induced animals are comparable with that of wild-type animals and significantly higher than non-induced animals (D, n = 4 animals in each group, p < 0.001).

(E) Immunohistochemistry showed before and after induction of insulin+ cells (first and second panel, respectively). STZ treatment was used at week 11 to ablate the induced insulin+ cells from the GI tract (third panel). Insulin+ cells were regenerated rapidly 3 weeks later (last panel). Ki67 staining labels the proliferating stem/progenitor cell compartment at the base of the glands. Scale bar, 100 μm.

All quantitative data presented as mean ± SD. Statistical significance was evaluated with the Student’s t test (∗∗∗p < 0.001). See alsoFigures S2 and S3.

To confirm that rescue from hyperglycemia results from induction of insulin+ cells in the GI tract, we surveyed insulin expression in other Ngn3-expressing tissues including the brain, testis, and pancreas. No insulin+ cells were found in the brain or testis (data not shown). In the pancreas of NRT animals, STZ treatment led to near complete ablation of endogenous β cells (Figure S2), but Dox treatment induced insulin in glucagon+ cells, which comprise the majority of islet cells after β cell ablation (Figure S2). These glucagon+insulin+ cells do not, however, express other β cell factors such as Glut2 and Nkx6.1, and their insulin expression level is significantly lower than in native β cells (Figure S2). To assess the possibility that these glucagon+insulin+ cells may nevertheless contribute to reversal of hyperglycemia after Dox induction in NRT animals, we resected ∼80% of the pancreas and thus most glucagon+insulin+ cells. No significant changes in blood glucose level followed (Figure 2A). The remnant 20% pancreas showed 0.15 ± 0.03 μg of total insulin (mean ± SD), significantly below the insulin content of antrum (1.89 ± 0.36 μg) or duodenum (1.20 ± 0.63 μg; Figure S4). In comparison, a normal mouse pancreas contains ∼10 μg insulin, although only a fraction of the β cell mass is required to maintain normoglycemia (Bonner-Weir, 2000). These data collectively indicate that induced insulin+ cells from the GI tract are the main source of secreted insulin that led to long-term reversal of hyperglycemia.

The GI tract is a highly regenerative organ, with resident glandular stem cells continuously producing new epithelial cells (Barker et al., 2010, Barker et al., 2007). To evaluate the capacity of GI β cell regeneration from the stem cell compartment, we conducted a second round of STZ treatment (Figures 2A and 2E). Similar to pancreatic β cells, induced insulin+ cells from the antrum and intestine were sensitive to the toxin and disappeared, leading to hyperglycemia (Figures 2A and 2E). However, the diabetic state was again rapidly reversed, concomitant with the reappearance of GI insulin+ cells (Figure 2E). These data illustrate the high regenerative capacity of the genetically engineered GI tissues and their ability to sustain injuries and maintain suppression of hyperglycemia.

We also evaluated the lifespan of antral and intestinal insulin+ cells and their relative contributions toward glycemic control (Figure S3). In a pulse-chase experiment, GI insulin+ cells were first induced by Dox treatment, followed by Dox withdrawal. Intestinal insulin+ cells disappeared within 7 days, whereas stomach insulin+ cells persisted for more than 20 days, consistent with estimated turnover rates of the native intestinal and antral epithelia (Karam and Leblond, 1993, Lehy and Willems, 1976, Messier and Leblond, 1960, Thompson et al., 1990). Antral insulin+ cells continued to suppress hyperglycemia after intestinal insulin+ cells had disappeared (Figure S3). Thus, antral insulin+ cells have a longer lifespan than their intestinal counterparts and can suppress hyperglycemia independently.

Antral Insulin+ Cells Bear Close Molecular and Functional Resemblance to Pancreatic β Cells

Immunohistochemistry revealed that induced insulin+ cells from the antral stomach and the proximal and distal intestine all express β cell factors such as c-peptide, glucose transporter 2 (Glut2, or Slc2a2), prohormone convertase 1/3 (PC1/3), and Pax6 (Figure 3A, quantification shown in Figure S4). However, other key β cell genes, including Nkx6.1, Nkx2.2, and prohormone convertase 2 (PC2), are expressed exclusively or predominantly in antral insulin+ cells (Figure 3A, quantitation shown in Figure S4). qPCR analysis further confirmed that many β cell factors are expressed at substantially higher levels in antral insulin+ cells than in duodenal or colonic insulin+ cells (Figure S4). Endogenous Pdx1, but not endogenous Mafa, is expressed in the native duodenum and antrum (Figure S4), as previously reported (Habib et al., 2012, Offield et al., 1996). Endogenous Mafa is activated strongly in antral insulin+ cells, but only weakly in duodenal and colonic insulin+ cells (Figure S4), whereas endogenous Pdx1 is induced in both antral and intestinal insulin+ cells (Figure S4). In contrast, endogenous Ngn3 is not induced (Figure S4). We observed continued expression of FoxO1 expression in both antral and intestinal insulin+ cells (Figure S4).

Print

Figure 3

Induced Insulin+ Cells from the Antral Stomach More Closely Resemble β Cells Molecularly and Functionally

(A) Immunohistochemistry showed that induced insulin+ cells from the antrum express β cell genes Nkx6.1, Nkx2.2, and Prohormone convertase 2 (PC2), which are largely absent from duodenum and colon insulin+ cells. In contrast, Prohormone convertase 1/3 (PC1/3), glucose transporter 2 (Glut2), and c-peptide (c-ppt) are expressed commonly in antral, duodenal, and colonic insulin+ cells. Arrows indicate antral insulin+ that are PC2+, Nkx2.2+, and Nkx6.1+. Scale bar, 50 μm.

(B) Glucose stimulated insulin secretion (GSIS) in vitro. Antral tissues have significantly higher glucose responsiveness, defined as fold increase of insulin release at high versus low glucose conditions, compared with duodenal and colonic tissues (n = 8, p < 0.001).

(C and D) The antidiabetic drug Glibenclamide (Glib) stimulated insulin release from the antral insulin+ cells whereas Diazoxide (Dzx), a suppressor of insulin release, reduced antral insulin secretion (C, n = 4). In contrast, duodenal and colonic insulin+ cells do not respond to Glib or Dzx (C). Antral insulin+ cells also respond to Exendin-4 (Ex4) with enhanced insulin secretion at high glucose levels whereas duodenal and colonic cells do not respond to Ex4 (D, n = 4).

All quantitative data presented as mean ± SD. Statistical significance was evaluated with the Student’s t test (p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001). See also Figure S4.

To assess functional properties of induced insulin+ cells from the stomach and the intestine, we harvested whole epithelial tissues from the antrum, duodenum, and colon of NRT animals after 10 days of Dox treatment. In vitro glucose-stimulated insulin secretion assays were performed with each sample at low-glucose (1.7 mM) and high-glucose (20.2 mM) conditions. Our data showed that although all GI insulin+ cells can respond to high glucose (Figure 3B), the responsiveness of antral insulin+ cells is significantly higher than that of duodenal and colonic insulin+ cells (Figure 3B; data standardized as high-glucose versus low-glucose response ratio: 3.02 ± 0.55 for antrum, 1.65 ± 0.37 for duodenum, and 1.61 ± 0.46 for colon).

To further evaluate the function of induced GI insulin+ cells, we tested their physiological response to glibenclamide (Glib), an anti-diabetic drug that binds to Sur1 and inhibits the ATP-sensitive potassium channel in β cells. Glib treatment led to insulin release from antral, but not from duodenal or colonic, insulin+ cells (Figure 3C). Conversely, treatment with Diazoxide (Dzx), a potassium channel activator, suppressed insulin release from antral insulin+ cells, whereas duodenal and colonic cells showed no response (Figure 3C). Moreover, antral insulin+ cells responded to exendin-4, an antidiabetic drug that activates glucagon-like-peptide receptor (Glp1R), leading to increased insulin release at high glucose concentrations (Figure 3D), whereas duodenal and colonic insulin+ did not respond (Figure 3D). Consistent with these physiological data, antral insulin+ cells express significantly higher levels of Sur1 and Glp1R, compared with duodenal and colonic insulin+ cells (Figure S4).

Thus, molecular and physiological studies together indicate that antral endocrine cells can be reprogrammed efficiently into insulin+ cells that resemble pancreatic β cells, whereas conversion from intestinal endocrine cells is comparatively incomplete.

Native Antral Endocrine Cells Share Substantial Transcriptional Similarity with Pancreatic β Cells

What mechanisms might underlie the significant difference? One long-standing hypothesis postulates that the more transcriptional and epigenetic similarities two cells share, the easier it is to interconvert them (Graf and Enver, 2009, Gurdon and Melton, 2008). Transcriptional studies of specific intestinal endocrine populations have been reported (Egerod et al., 2012, Habib et al., 2012), but transcriptomes of antral endocrine cells remain uncharacterized. We therefore profiled the transcriptomes of enteroendocrine cells from the antrum, duodenum, and colon and assessed their similarity to pancreatic β cells. We used Ngn3-GFP reporter mice to isolate enteroendocrine cells from the different GI regions (Lee et al., 2002); Ngn3 expression in the gut is transient and restricted to endocrine progenitors (Jenny et al., 2002, Lee et al., 2002). Ngn3-GFP labels a mixture of chromogranin− (Chga−) and chromogranin+ (Chga+) cells, representing immature and mature endocrine cells, respectively (Lee et al., 2002) (Figure 4A). Our quantitation showed that the relative proportions of GFP+Chga− and GFP+Chga+ cells are comparable in antral stomach, duodenum, and colon (Figure S5). GFP+ cells purified by FACS from the different GI regions (Figure 4B) constitute ∼1%–2% of the total cell population (Figure 4B), consistent with the estimated prevalence of gut endocrine cells (Schonhoff et al., 2004a).

Fig1 TA

Figure 4

Enteroendocrine Cells of the Antral Stomach Share Substantial Transcriptional Similarity with Pancreatic β Cells

(A) Immunohistochemistry showing distribution of GFP+ in the GI tract of the Ngn3-GFP mouse line. The GFP+ cells include both relatively immature (GFP+Chromogranin) and more mature enteroendocrine cells (GFP+Chromogranin+). Scale bar, 50 μm.

(B and C) Ngn3-GFP+ cells were purified by FACS from antrum, duodenum, and colon (B). Scatterplots of transcriptome comparisons between pancreatic β cells and the GI enteroendocrine populations (C). Antral enteroendocrine cells show a greater similarity with β cells.

(D and E) Analysis of 2,398 β cell-enriched genes showed a general trend of elevated expression in antral enteroendocrine cells compared with duodenal and colonic enteroendocrine cells (D). In particular, antral enteroendocrine cells share a group of genes (group 2) with β cells (D) that are enriched for factors important in β cell development and function (E). Quantitative data presented as mean ± SD. Statistical significance was evaluated with the Student’s t test (p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001).

(F) Immunohistochemistry showed that Nkx6.1 is present in a population of Chga+ enteroendocrine cells in the antrum, but not expressed in duodenum or colon (top, arrows). Nkx2.2 is expressed in a majority of Chga+ enteroendocrine cells in the antrum and a minority of Chga+ cells in the duodenum and colon (F, bottom, arrows). Scale bar, 50 μm.

See also Figure S5.

We generated global transcriptome data from the purified cells with Illumina arrays. Comparative analyses showed that endocrine cells from the proximal and distal intestine are more similar to each other and less similar to antral endocrine cells (Figure S5, Spearman correlation coefficients: 0.91 [duodenum versus colon], 0.82 [antrum versus duodenum], and 0.80 [antrum versus colon]). The overall similarity of proximal and distal intestine endocrine cells is high and consistent with published studies (Egerod et al., 2012, Habib et al., 2012) (1,470 differentially expressed genes listed in Table S3). We performed pairwise comparison of the three GI endocrine populations with our published transcriptome data of β cells, which was obtained by FACS purification from the islets of MIP-GFP animals (Li et al., 2014b). This analysis showed overall higher transcriptional similarity between antral and β cells than between intestinal and β cells (Figures 4C and S5, Spearman correlation coefficients: 0.72 [antrum versus β], 0.57 [duodenum versus β], and 0.57 [colon versus β]; Steiger’s Z-test for dependent correlations: p = 6.5 × 10−185). Thus, although enteroendocrine cells from the antrum, duodenum, and colon are more similar to each other than they are to pancreatic β cells, β cells appear to share more transcriptional similarity with antral enteroendocrine cells than intestinal enteroendocrine cells.

To evaluate the expression of β cell-enriched genes in GI enteroendocrine cells, we focused analysis on a collection of 2,398 genes that show higher expression in β cells than in acinar cells (Li et al., 2014b). Antral enteroendocrine cells showed higher expression of many β cell-enriched genes (Figure 4D, group 2 and 3 genes; Table S2) compared with intestinal enteroendocrine cells. In particular, many genes critical for β cell development and function, such as Nkx6.1, Nkx2.2, NeuroD1, Isl1, Rfx6, Insm1, Sur1 (ABCC8), and Glucokinase (GCK), are enriched in antral, compared with duodenal or colonic, enteroendocrine cells (Figures 4E and S5). Immunohistochemistry showed Nkx6.1 expression in a subset of antral GFP+ cells (24.9% ± 3.5%, mean ± SD), but not in the duodenum or colon (Figure 4F). The vast majority of antral Nkx6.1+ cells also express Chga (94.7% ± 3.1%) (Figures 4F and S5). Nkx2.2 is expressed in a majority of GFP+ cells in the antrum (57.2% ± 4.7%), but only in a minority of duodenal (18.7% ± 2.7%) or colonic (23.4% ± 4.3%) Chga+ cells (Figure 4F). Most Nkx2.2+ cells express Chga (69.4% ± 3.4%, 64.0% ± 5.1%, and 65.5% ± 8.3% in antrum, duodenum, and colon, respectively) (Figure 4F; Figure S5). Gene Ontology analyses show that whereas enteroendocrine cells from all GI regions are enriched for pathways involved in regulation of hormone secretion, G-protein-coupled receptor signaling, and vesicle-mediated transport, antral enteroendocrine cells are enriched specifically for the “glucose homeostasis” module (Figure S5; Table S2). Together, these studies reveal a surprising intrinsic difference between endocrine cell populations from the antral stomach and intestine, which likely contributes to their differential capacity for β cell reprogramming.

The Intestine-Specific Gene Cdx2 Can Inhibit β Cell Conversion

In a prior study of acinar to β cell conversion, we showed that persistent expression of acinar cell fate regulators Ptf1a and Nr5a2 blocks acquisition of β cell fate (Li et al., 2014c). Cdx2 is an intestine-specific master regulator gene (Gao et al., 2009), and its persistent expression in intestinal insulin+ cells (Figure 5A) raises the question of whether Cdx2 might block intestinal cells from adopting more complete β cell features. To test this hypothesis, we generated epithelial organoids from the antrum and duodenum of double transgenic Rosa-rtTA;TetO-NPMcherry (Rosa-NPM) animals and treated them with Dox in culture. Similar to our observations in vivo, antral organoids produced more C-peptide+ cells with higher levels of β cell factors compared with intestinal organoids (Figure S6). Next, we expressed either the control cherry gene or Cdx2 using adenoviral infection in the double-transgenic antral organoids (Figures 5B and 5C), followed by treatment with Dox to activate β cell conversion. Cdx2 significantly suppressed expression of multiple β cell genes, including NeuroD1, Nkx2.2, and Nkx6.1 (Figure 5D).

Print

Figure 5

The Intestine-Specific Cell Fate Regulator Cdx2 Can Inhibit β Cell Conversion

(A) Duodenal and colonic insulin+ cells express Cdx2, the master regulator of intestine cell fate whereas antral stomach cells do not express Cdx2 before or after induction in NRT animals. Scale bar, 50 μm.

(B–D) Epithelial organoids were established from antral tissues of double-transgenic Rosa-rtTA;Teto-NPMcherry (Rosa-NPM) animals and infected with either control adenovirus expressing Cherry (pAd-cherry) or adenovirus expressing Cdx2 and Cherry (pAd-Cdx2.cherry) (B and C). Dox treatment was subsequently used to induce β cell conversion in these antral organoids. qPCR analysis showed that ectopic Cdx2 suppressed the expression of multiple β cell genes (D, n = 3). Scale bar, 100 μm.

(E–G) Duodenal organoids were established from Cdx2fl/+ and Cdx2fl/fl animals (E, left and right, respectively). Infection with an adenovirus co-expressing both NPM factors and the Cre recombinase led to simultaneous deletion of floxed Cdx2 allele and expression of NPM factors (E). Complete removal of Cdx2 was observed in majority of Cdx2fl/fl duodenal cells by immunohistochemistry and qPCR analysis (E and F) and led to enhanced expression of multiple β cell genes from the duodenal organoids (G, n = 3). Scale bar, 100 μm.

Quantitative data presented as mean ± SD. Statistical significance was evaluated with the Student’s t test (p < 0.05, ∗∗p < 0.01, and∗∗∗p < 0.001). See also Figure S6.

To further evaluate the role of Cdx2 in intestine reprogramming, we deleted Cdx2 from duodenal organoids. We established duodenal organoids from animals where a single allele or both alleles of the Cdx2 gene are floxed (Figure 5E, Cdx2fl/+ and Cdx2fl/fl). Infection with an polycistronic adenovirus expressing NPM factors and the Cre recombinase (pAd-NPM.Cre) led to simultaneous removal of the floxed Cdx2 allele(s) and expression of NPM factors (Figure 5E). Immunohistochemistry and qPCR confirmed complete removal of Cdx2 from the majority of Cdx2fl/fl duodenal cells (Figures 5E and 5F). Cdx2 deletion significantly enhanced expression of several β cells genes, including Insulin1, insulin2, Nkx6.1, and NeuroD. These data together suggest that Cdx2 acts as a molecular barrier to β cell conversion; thus, failure to downregulate Cdx2 in intestinal insulin+ cells likely contributes to their incomplete acquisition of β cell properties.

Constructing Bioengineered Stomach and Intestine Mini-organs to Produce Insulin+ Cells

Among GI tissues, antral stomach is a superior source of functional β cells by NPM-mediated conversion, and antral insulin+ cells are rapidly replenished from the native stem cell compartment. However, inducing β cells from the native GI tract in situ may have limitations in therapy, because the native endocrine populations regulate many physiological processes (Field et al., 2010, May and Kaestner, 2010, Schonhoff et al., 2004a), and diverting them into β cells may disrupt normal endocrine homeostasis. Moreover, induced β cells positioned along the native GI epithelium may inadvertently respond to dietary as well as blood glucose. To circumvent these potential barriers to therapeutic application, we studied the feasibility of constructing “stomach mini-organs” that contain genetically engineered antral tissues as a reservoir of new β cells.

Following published protocols on bioengineering stomach (Maemura et al., 2004, Speer et al., 2011), we embedded gastric gland units from the antrum of CAGrtTA::TetO-NPMcherry (CAG-NPM) animals in Matrigel, loaded them onto poly(glycolic acid) (PGA) scaffolds, and transplanted the material into the omental flap of immunodeficient NSG recipient animals (Figures 6A–6C). Four weeks later, bioengineered stomach spheres measuring 0.5 to 1 cm in diameter formed outside the native gut (Figure 6D). By histology, 5 out of 15 such spheres showed robust epithelial reconstitution, while the others showed little or no epithelium (Figure S7). Antral glands in the native stomach are composed largely of mucous and endocrine cells and lack acid-secreting parietal cells. The engineered stomachs also showed a simple organization, with one or several layers of Ecadherin+ cells surrounded by connective tissue (Figure S7). The epithelial component contained Sox9+ stem/progenitor cells (Furuyama et al., 2011), Mucin5+ secretory cells, and Chga+ endocrine cells (Figure S7). In parallel, we used a similar bioengineering approach to construct “intestine mini-organs” using duodenal gland units. The success rate for epithelial reconstitution was lower in intestinal spheres (3 out of 15), which contained Muc2+ secretory cells and Chga+ endocrine cells, similar to the native duodenal epithelium. Our observations are consistent with other published studies on bioengineered stomach and intestine (Maemura et al., 2004, Speer et al., 2011).

Fig4. TA

Figure 6

Construction of Bioengineered Stomach and Intestine Mini-organs to Produce Insulin+ Cells

(A–K) Schematic diagram of engineering stomach and intestine mini-organs (A). Gastric or intestinal units were isolated from the antrum or duodenum of CAG-NPM (Cag-rtTA::TetO-NPMcherry) animals (B and I) and loaded onto polyglycolic acid scaffolds (C and J). The scaffolds were placed inside the omental flap of recipient immune-deficient NSG animals. 4 weeks later, an engineered stomach (E. St) or intestine (E. Int) sphere formed (D and K, circled tissue). Scale bars represent 400 μm (B and I) and 6 mm (C and J).

(E–R) In engineered stomach and intestine spheres where reconstitution of epithelium was successful, Dox treatment led to induction of many insulin+ cells (E and L). The induction efficiency is higher for stomach tissues (P, n = 3). Stomach tissues also have higher insulin content (Q, n = 3). The majority of insulin+ cells from engineered stomach express Nkx6.1, PC1/3, and Glut2 (F, G, H, and R) whereas insulin+ cells from engineered intestine lack Nkx6.1 and have reduced PC1/3 expression (M, N, O, and R). Quantitation presented as mean ± SD. Statistical significance was evaluated with the Student’s t test (∗∗p < 0.01 and ∗∗∗p < 0.001).

See also Figure S7.

To evaluate induction of insulin+ cell in the engineered stomach and intestine spheres, we administered Dox for 2 weeks. Many insulin+ cells appeared in the epithelial layer of stomach as well as intestinal spheres. The stomach spheres had significantly more insulin+ cells, higher reprogramming efficiency, and higher insulin content per milligram of tissue (Figures 6E, 6L, 6P, and 6Q). The majority of stomach insulin+ cells express Nkx6.1, Glut2, and PC1/3, whereas intestine insulin+ cells lack Nkx6.1 and have reduced PC1/3 expression (Figures 6F–6H, 6M–6O, and 6R).

Transplanted Stomach Mini-organs Can Control Hyperglycemia in Diabetic Mice

To assess if β cells induced in the engineered stomachs could release functional insulin, we ablated pancreatic β cells in transplanted animals using STZ and then induced insulin+ cells in the engineered stomach spheres by administering Dox (Figure 7A). Of the 22 treated animals, 5 showed sustained decreases in blood glucose levels after Dox treatment (group 1), whereas the others remained hyperglycemic (group 2) (Figure 7B). We monitored animals for 6 weeks and subsequently removed the grafted stomach spheres from G1 mice, which restored hyperglycemia (Figure 7B). Engineered stomach spheres from G1 animals showed good epithelial structures containing many insulin+ cells (Figure S7), whereas spheres from the G2 groups showed limited epithelial structures with few insulin+ cells (Figure S7). Consistent with the glucose monitoring data and histology, G1 animals showed improved responses to intraperitoneal glucose challenge (Figure 7C). Blood insulin levels in G1 animals also were substantially higher than in G2 animals (Figure 7D).

Fig7. new

Figure 7

Transplanted Stomach Mini-organs Can Reverse Hyperglycemia in Diabetic Mice

(A) Diagram of the experimental design. STZ treatment was used to ablate endogenous β cells in NSG animals transplanted with 4-week-old stomach spheres, followed by continuous Dox treatment of induce insulin+ cells. At the end of the experiment, the engineered stomachs were removed surgically.

(B–D) STZ treatment led to rapid hyperglycemia that persists in the absence of treatment (−Dox group, n = 6, black squares) (B). After Dox treatment, a group of five animals showed prolonged suppression of hyperglycemia (G1 animals, n = 5, red squares), whereas another group of animals remained hyperglycemic (G2 animals, n = 17, blue squares) (B). After 6 weeks, the engineered stomach spheres were removed from the G1 animals, which led to their reversal back to hyperglycemia (B). G1 animals showed improved response in glucose tolerance test (C, n = 4) and substantially higher blood insulin levels (D, n = 4) compared with G2 animals or control STZ-treated animals without Dox induction. Wilde-type control animals in (C) (green squares) are non-STZ-treated animals with intact pancreatic β cell mass. Quantitative data presented as mean ± SEM. Statistical significance was evaluated with the Student’s t test (∗∗∗p < 0.001).

(E–G) Sox9+ and Ki67+ cells are present in the engineered stomach after 4-week Dox treatment (F and G), indicating persistence of stem/progenitor cells. PEcam+ blood vessels are closely associated with insulin+ cells inside the engineered stomach sphere (E). Scale bars, 100 μm. Blue channel, DAPI.

See also Figure S7.

Immunohistochemistry revealed PEcam+ blood vessels closely associated with insulin+ cells in engineered stomach spheres (Figure 7E), consistent with previous observations that induced β cells, similar to endogenous β cells, can secrete VEGF and remodel local vasculature (Zhou et al., 2008). Moreover, large numbers of Sox9+ stem/progenitor cells and Ki67+ proliferating epithelial cells are present in the engineered stomach spheres before and after Dox treatment, indicating persistence of a stem/progenitor compartment (Figures 7F and 7G). These studies collectively indicate that induced insulin+ cells from the bioengineered stomach spheres can release insulin into the circulation and regulate blood glucose levels.

Discussion

The GI tract is a highly regenerative endodermal organ. We sought to harness this regenerative capacity to create a renewable source of functional insulin+ cells by NPM-mediated reprogramming. Our data show that antral stomach enteroendocrine cells are converted to insulin+ cells more efficiently than intestinal enteroendocrine cells and possess molecular and functional hallmarks of pancreatic β cells. Thus, the antral stomach is a surprisingly good source for reprogrammed insulin+ cells, and we demonstrate the application of bioengineered stomach spheres to control blood glucose levels.

Expression of NPM factors previously led to formation of insulin+ cells in the intestine (Chen et al., 2014). Our experimental system is similar to this previous report and confirms induction of insulin+ cells in the intestine with incomplete β cell conversion. In contrast, antral stomach endocrine cells are more fully reprogrammed, with robust expression of key β cell genes and substantially improved glucose responsiveness. Our studies suggest that the difference can be attributed, at least in part, to intrinsic molecular differences between antral and intestinal enteroendocrine cells. Higher levels of β cell fate regulators in antral enteroendocrine cells may facilitate their conversion, whereas Cdx2, which is specifically expressed in all intestinal, but not stomach, cells inhibits conversion. It is notable that Cdx2 expression persists in induced insulin+ intestinal cells. Prior studies have shown that ectopic Cdx2 expression in stomach promotes an intestine fate (Silberg et al., 2002, Verzi et al., 2013), whereas Cdx2 loss in cultured intestinal organoids activates antral differentiation (Simmini et al., 2014). Continued expression of Cdx2 in intestinal insulin+ cells may thus present a molecular barrier for complete reprogramming.

Compared with the gastric antrum, the gastric corpus contains few Ngn3-derived enteroendocrine cells, and few such cells expressed insulin after NPM induction. Global expression of NPM factors also induced few insulin+ cells in the fundus (Figure S1). Thus, gastric corpus endocrine cells, which are distinct from those in the antrum or intestine (Choi et al., 2014, Li et al., 2014a) and mainly derive from Ngn3-independent lineages (Li et al., 2014a, Schonhoff et al., 2004b), are not amenable to NPM-mediated β cell conversion. What might account for this resistance? The antral stomach shares a close developmental origin with the pancreas, with both organs arising from a common Pdx1+ endodermal domain during embryogenesis (Wells and Melton, 1999). Therefore, we speculate that the epigenetic landscape of endocrine cells from the fundus is more distinct than those from the antrum, making them harder to convert into β cells. Future studies will be necessary to understand these regional distinctions.

FoxO1 deletion also leads to formation of insulin+ cells in the intestine, suggesting a therapeutic path toward inducing insulin+ cells in situ (Bouchi et al., 2014, Talchai et al., 2012a). Our approach offers several advantages. First, with our method, induced insulin+ cells preserve FoxO1 function, which is known to protect β cells from physiologic stress (Kitamura et al., 2005, Talchai et al., 2012b). Second, with bioengineered stomach spheres, native endocrine cell populations in the gut remain undisturbed, and their functions in physiology are preserved. Third, by separating engineered stomachs from the native organ, induced β cells can be positioned to respond only to changes in blood and not luminal glucose levels.

In summary, our study offers a new approach to harness the intrinsic regenerative capacity of the stomach epithelium to replenishing β cell mass in vivo. Given ongoing pathological insults that continuously erode native or transplanted β cells in diabetes, long-term treatment may require repeated transplants. The regenerative system we propose could eliminate that need, and the number and size of transplanted stomach spheres could be manipulated to control β cell numbers. Coupled with recent progress in genome engineering and the ready access to human gastric epithelium from biopsies and differentiated induced pluripotent stem cells or embryonic stem cells (McCracken et al., 2014), the therapeutic applications of this approach are considerable.

To view the full article click here.

To view a PDF version click here.

Learn More +

New Class Of Antigens Might Help In Diagnosis And Treatment

the-new-antigens-result-in-the-formation-of-hybrid-insulin-peptides

Original article written by R. Siva Kumar for Counsel & Heal on February 15, 2016. Click here to read the original article.

A novel class of antigens might help scientists to understand why type 1 diabetes develop, finds research from a University of Colorado Denver.

This type of diabetes has the immune system turning against the body’s own tissues. The type 1 diabetes shows that insulin-producing beta cells identified in the pancreas are hit by immune cells, especially T cells.

The insulin is a hormone vital for maintaining blood glucose, and without it, things can become threatening for life. Results can help scientists to invent the first-ever cure for this form of diabetes.

“Our lab studies the type of T cell known as a CD4 T cell,” Kathryn Haskins, corresponding author of the article, said in a press release. “We have focused on autoreactive CD4 T cells using a mouse model of autoimmune diabetes. We have been especially interested in identifying the antigens that activate these T cells.”

Such antigens can also help to find autoreactive T cells in the early stage of the disease and in those who are at risk. It helps in the identification and treatment too. By developing a way of turning off harmful T cells, they may be able to prevent the illness.

There may be some modified peptides that are called “foreign” to the human immune system. Some of these become targets for autoreactive T cells. Other autoimmune diseases can also be understood through them.

The study was published in the Feb. 12, 2016 issue of Science.

Learn More +
Diabetes Research Connection Logo

The 2015 Pediatric Research That Should Change Practice

Original article written by Alan Greene, MD and Laurie Scudder, DNP, PNP for Medscape Pediatrics on February 11, 2016. Click here to read the original article.

Editor’s Note:
Keeping up with the relentless body of literature in specialty journals is a daunting task for pediatric primary care providers. Nevertheless, keep up they must; much of this new research affects day-to-day practice and, crucially, early detection and management of numerous conditions that first present in the primary care setting. Medscape spoke with Alan Greene, MD, a Medscape advisor, adjunct professor of pediatrics at Stanford University School of Medicine, and founder and CEO of DrGreene.com, about his picks of the most interesting and important studies in 2015 and their implications for practice.

Medscape: A number of studies in the last 12 months have added yet more urgency to the concerns regarding the dangers of child obesity. A paper[1] relying on data from recent National Health and Nutrition Examination Surveys (NHANES) found that less than 1% of US children had an ideal healthy diet score. Type 2 diabetes rates are rising, and another paper[2] found that long-term complications and mortality were worse in these children than their counterparts with type 1 diabetes. New data show that sweetened beverages, including milk products, are a major contributor to obesity.[3] Yet another study, this one conducted in Iran, found that breastfeeding is protective well into childhood.[4] Despite our growing recognition of factors that contribute to obesity, a solution is still elusive and difficult. What are your key take-away messages from the last years’ worth of research, and how do you suggest making it practical and implementable in the primary care setting?

Dr Greene: The study examining NHANES data[1] is striking in that it was looking for a measurable index of cardiovascular (CV) health in kids so that we could see where we are and where we’re going in the future as lifestyle and interventions change. By and large, the researchers found that the overwhelming majority of babies enter the world with pristine CV systems, with hearts and blood vessels that are supple, powerful, and beautiful. However, by the time they are adolescents, under our watch as pediatricians, the great majority of children have already developed significant CV risk factors.

This is a fairly recent phenomenon. When I started in pediatrics, it was very unusual to see a child with elevated blood pressure. Today, there are millions of children in the United States with elevated blood pressure. It used to be unusual to see kids with elevated serum cholesterol or triglycerides or with a waist size of 36 or 40 inches. It was unusual to see kids with elevated glucose unless they had type 1 diabetes.

Today, two thirds of American middle school and high school students already have at least one of those conditions that used to wait until middle age. These data add urgency to the obesity epidemic we currently see. It’s a metabolic ticking time bomb.

The study examining children with young-onset diabetes[2] was equally eye-popping. Traditionally, many of us breathe a sigh of relief when we hear that diabetes is type 2 as opposed to type 1. We know the severity of type 1 diabetes in kids. But this study found that type 2 diabetes in childhood and adolescence actually has more morbidity and greater mortality than type 1, the opposite of that traditional wisdom. We should be even more concerned with kids when they develop type 2 diabetes.

This finding was shocking to me, and I pay close attention to this literature. It lends, again, more urgency to the situation. One little side note from this study is about sweetened beverages as a contributor not just to obesity but to type 2 diabetes. We are already aware of the link between obesity and sugary drinks, sugary sodas, juices, and juice-like beverages. But this study found a strong association with chocolate milk and sweetened milk and type 2 diabetes.

Given this new urgency regarding the risks of diseases comorbid with obesity, what do we do? There are a few things. This is a dominant medical issue of our time, and it belongs as part of every well child visit, something that we’re measuring and tracking over time and helping families to learn key messages with every visit. In early childhood, especially in the first couple of years of life, feeding early and often the flavors and textures that you want kids to learn to love can have a profound trajectory on what kids learn to like and is the key to building good food habits from the start. We need to encourage family meals from the beginning, tell parents to not give up on vegetables, introduce a lot of variety, and serve something green at every lunch and every dinner.

Once kids have really set their initial tastes, by around age 2 or 3 years, one of the most effective ways to get them to like better food is to have them involved in the process, to have family meals at home where everybody is eating some of the same food. In particular, get kids involved in meal prep, go to the farmer’s market to select the foods, and, for families that have the option, get kids involved in growing real food. Cooking classes are one of the most fun things that parents can do with children to get them involved in preparing food they will enjoy and that their bodies will also enjoy.

Medscape: Those are recommendations that are easily implemented and understood by families and provide good advice for clinicians practicing in more resourced areas. But what about those kids who live in stressed, urban environments? Are there practical suggestions for those families that we are missing?

Dr Greene: Smartphones are very prevalent in less advantaged communities. One of the key nutritional barriers these families face, families that reside in food deserts where healthy food is difficult to access, is finding interesting and tasty foods among what is available and learning which foods are the healthiest.

One free Smartphone app that I like is Fooducate. The app allows you to scan any barcode, gives you a letter grade (A, B, or C) for how healthy that food is, and suggests others in the same category that might be healthier. The app ranks foods on both flavor and nutrition and can help lead consumers in a positive direction.

Medscape: This sounds like the kind of thing children would find fun to do at a store.

Dr Greene: Exactly. It’s a great way to eliminate food battles at a grocery store. Parents can tell children they can pick anything that’s a B or better.

Sodium: The Underreported Food Concern for Children

Medscape: Another report,[5] also based on data from NHANES, concluded that US school-aged children, on average, consume sodium in excess of recommended levels regardless of age, sex, race/ethnicity, income, or weight status. Unlike the attention paid to sweetened beverages, sodium doesn’t get as much press. What is the current state of evidence regarding hazards of excessive sodium intake in children?

Dr Greene: Sodium often doesn’t get enough attention. To provide some context, in the early 1970s, Finland had the highest rate of hypertension and one of the highest levels of CV disease, heart attacks, and stroke of any country on the planet. As a country, they decided to take that on and implemented a number of population-wide public health measures, and they were able to get their average national blood pressure down to normal. One of the big ones was that they decreased the average sodium intake by over 25% to reach recommended levels. It had a profound national impact. Very seldom do you see such a major public health advance.

The Centers for Disease Control and Prevention estimates that if we could reach the recommended sodium intake level of 2300 mg/person/day in the United States—perhaps even a generous recommended level—that we would save between 280,000 and 500,000 lives over the next 10 years, not to mention the improved health, brain health, and physical activity that could be had. It’s a big issue. This study published in the MMWR looked at sodium intake among school-aged kids and found that the average daily sodium consumption in children was 3279 mg/day, almost 1000 mg/day above the recommended level of 2300 mg/day. Consumption is even higher among high school students. Most of the sodium intake comes from 10 food categories together: pizza; breads and rolls; cold cuts; savory snacks; sandwiches; cheese; chicken patties, tenders, or nuggets; pasta mix dishes; Mexican mix dishes, and soups.

Becoming more aware of sources of sodium in the average child’s diet and looking for options that are made flavorful can have a profound impact. Sodium, especially in processed foods, is often hidden. People are aware that there is sodium in their fast food French fries. They may not be aware that the milkshake may have more sodium than the French fries.

Sleep: Kids Are Just Not Getting Enough

Medscape: The importance of sufficient sleep as a major contributor to both physical and psychosocial well-being is increasingly recognized. In late 2014, the American Academy of Pediatrics Adolescent Sleep Working Group issued a policy statement[6] urging schools to consider delaying start time in order to allow middle and high school students to achieve sufficient sleep. Dealing with sleep and sleep-related problems, however, can be daunting, particularly in a primary care setting with limited time. Can you summarize the latest research examining brief interventions that can be deployed in the primary care setting to promote healthy sleep?

Dr Greene: I do think that one of the roles of pediatricians is advocacy. The literature would suggest that delaying school start timesto at least 8:30 in the morning would improve health in a variety of ways, including reductions in obesity, hypertension, and attention-deficit/hyperactivity disorder. It would improve mood, decrease depression and suicidal thoughts or actions, and decrease car accidents in teen drivers.

Where this change has been implemented, that is exactly what has been found. This is an intervention that works, but many school districts are reluctant to adopt this change for a variety of practical reasons. It’s a great issue, and pediatricians should get involved by speaking, writing or calling their local school board, and letting their community know that we as a profession are behind this. The Academy of Pediatrics is behind it, but we as local pediatricians must also say clearly that we are behind it.

As far as things to do in the office, one of my favorites is to try to support the circadian rhythm, so named because it’s “circa dian.” It’s about a day. For most of us, it would be about a 25-hour rhythm where not only do we have sleepiness and arousal that rise and fall, but we also have fluctuations in blood pressure, body temperature, and many hormones. It is a profound rhythm that we share with other living beings that is reset daily by certain cues from the environment. We are seasonal creatures. If we were in a cave and had none of these external cues, our circadian rhythm would eventually get completely off from other people in the external world. But for us, that rhythm is reset by something called zeitgebers.

Zeitgebers are our friends. The more they are in line with each other and the more they are consistent, then the better, longer, and deeper sleep we have. The most profound zeitgeber is probably light. We are very light-sensitive creatures. When we look back before the invention of the electric light bulb, kids tended to sleep like a baby—all night long, soundly, profoundly without waking up, even if there was a loud noise. Today sleeping like a baby often means waking up crying every couple of hours. Sleep for teenagers is often something that’s disrupted as well. Childhood sleep is not as peaceful as it used to be.

One thing that we can do is try to keep the environment as dim as possible between sunset and sunrise. That can have a profound impact on sleep. When you’re camping, you tend to get very drowsy a couple of hours after sunset. That’s difficult in our modern, urban, digital life, but the more we can at least remove the wavelengths of light that trigger melatonin suppression, the easier it is to sleep.

That means paying attention to screens. There are now apps for a variety of different computer and smartphone screens that will pull out the blue wavelength of light, about 475 nm. You can get light bulbs that pull out that wavelength of light in the evening or wear blue-blocker sunglasses to get rid of it. There is a pigment in the retina, melanopsin, that responds to a 475-nm signal and suppresses melatonin or disorganizes it for the rest of the night. Eliminating that sunset to sunrise is a rather simple thing that can help people get drowsy earlier. Part of that means not viewing screens in the last hour or so before bed at least.

Another strong zeitgeber is temperature. For most of the history of humanity, we have experienced our evenings and nights as much cooler than daytime; but with central air and central heating, we have compressed our temperature window in a very narrow range. Creating a cooler nighttime environment, 7 degrees cooler or more, helps with falling and staying asleep.

 

Iron Status in Infants: Does It Matter?

Medscape: Delaying cord clamping after birth for approximately 3 minutes has been demonstrated to result in improved iron stores in infants up to 4 months of age.[7] A follow-up paper[8] published earlier this year examined the effects of those increased iron stores on neurodevelopment and concluded that the practice benefits fine motor and social skills in early childhood, particularly among boys. This finding is in contrast to a systematic review[9] that concluded that while there may be some evidence demonstrating that routine iron supplementation in children 6-24 months of age may improve hematologic values, evidence of an improvement in clinical outcomes, including developmental outcomes, is lacking. How should pediatric providers be monitoring—and potentially addressing—iron insufficiency in young children?

Dr Greene: The systematic review[9] article earlier this year did suggest that there is not conclusive evidence that testing for iron deficiency anemia by checking hemoglobin and hematocrit and then supplementing with iron does anything to improve developmental outcomes. You can change the hematologic indices, but we may or may not be able to change the cognitive deficits and behavior problems that we do see with iron deficiency.

That review is still somewhat controversial. These researchers were not able to detect a difference in development with screening and subsequent iron supplementation. The US Preventive Services Task Force also now thinks that there is insufficient evidence to recommend routine iron screening.[10] Of note, the issue of iron supplementation was called into question this year with publication of a very interesting paper[7] suggesting a powerful impact from an easier intervention. That is something I would call optimal cord clamping. It’s often called delayed cord clamping in the literature, but I favor the term “optimal.” I don’t think it’s delayed.

The story here is that at the moment a baby is born, about a third of their blood is still circulating in the placenta and umbilical cord. For most of human history, people would watch the cord pulse and pump blood into the baby, largely eliminating iron deficiency anemia. With that blood, the cord would also pump in oxygen, oxygen-carrying capacity in the red blood cells, white blood cells, antibodies, stem cells—a whole host of good things.

But in the early 20th century, the medical community decided to clamp the cord immediately after birth so that we could examine the child. In doing that, we separated ourselves from our history as a species. It’s not just us. There is not one known mammalian species that actively cuts the cord prior to it stopping pulsing.

The idea of waiting an extra maybe 90 seconds to 3 minutes after the baby is born is now supported by published studies looking at the neurodevelopment in kids that had this extra bolus of iron at birth as humans typically had in the past; researchers found improved fine motor and social skills years later, particularly in boys.[11] That’s a zero-cost and easy way to help kids start off with a better iron store.

The American Academy of Pediatrics recommends that exclusively breastfed kids be supplemented with iron.[12] I think that’s a reasonable thing to do, but it kind of raises the question of why? Breast milk is presumably the perfect food, the ideal food for human babies. Why would it not have enough iron? There are two important nutrients that kids seem to need that are not present in breast milk. One of those is vitamin D, and that makes sense because historically we got very little vitamin D from breast milk and a lot of it from the sun. Now that children spend most of their childhood indoors, they need another source.

The second nutrient is iron. Is that because the kids weren’t getting iron supplements or iron-fortified cereals throughout history? I think the reason is that kids historically got a big bolus of iron from a different direction, and restoring that would be a simple way to help improve iron status throughout childhood.

Medscape: You note that the rationale behind earlier cord clamping was to allow examination of the child. Were concerns about maternal-fetal transfusion another reason for implementation of immediate clamping?

Dr Greene: There wasn’t a concern at the time about jaundice or maternal-fetal transfusion. The change happened around 1913. One of the big reasons was a concern about maternal hemorrhage. The thought was that immediate clamping would be safe for the baby and safer for the mom in terms of hemorrhage.

It turns out that earlier clamping did nothing to reduce hemorrhage. And while it did allow quick examination and resuscitation of the child if necessary, you don’t need to clamp the cord to examine and resuscitate a child. The extra blood and oxygen that the infant is getting during that golden minute is exactly what we’d want to be giving them anyway.

 

What About the Microbiome?

Medscape: The microbiome continues to be a fascinating area of research with better recognition that microbiota are ecologically engineered by mothers and breastmilk. Can you review what we’ve learned in the last year, particularly in regard to the influence of breast milk on both fetal and postnatal development?

Dr Greene: There are a number of risk factors that we know influence the odds that a child will end up developing allergies. Examples are type of delivery (caesarean vs vaginal), exposure to smoking in the household, pets or no pets, birth order of the child, urban vs rural residence, and breast-fed vs formula-fed.

The thing that is striking is that all of those seemingly separate risk factors each have a profound influence on the developing microbiome in the baby. The microbiome may be the common pathway in the development of allergic disease, atopic disease, and eczema.

It is surprising to learn that there are more than 200 ingredients in breast milk that are not digestible and do not directly nourish the baby. Why are they there? Well, it turns out that they cultivate a particular microbiome and nourish the bacteria colonizing the infant’s gut.

There are a growing number of studies that provide evidence of a long shadow from the microbiome that colonizes a child. In particular, some of these studies are looking at the relationship between the type of bacteria with which a child is colonized, short-term symptoms like cough, and long-term symptoms like childhood obesity.

One of the things that we have learned is that, in addition to the gut microbiome that is most familiar to us, there is also a genital microbiome. There is a skin microbiome, varying skin microbiomes, an oral microbiome, and the nasal microbiome.

Recently we’ve learned that the placenta, which we used to think was sterile, has its own microbiome. The developing baby is influenced by a community of bacteria as well. It turns out that the placental microbiome that people thought would be similar to mom’s vaginal microbiome is not, nor is it similar to the gut microbiome. It is actually closest to the oral microbiome for reasons we haven’t really learned yet.

Just prior to birth, the infant gut is sterile. However, the gut is colonized early on, and that early colonization depends on two things. First, it depends on what bacteria the baby is exposed to early on. For a caesarean -section baby, the first bacteria may be mom’s skin bacteria. For a vaginally delivered infant, that exposure may be vaginal and gut bacteria. Maternal stool is often involved in delivery, and that may be a nonaccidental part of the system.

The second factor that affects early infant gut colonization is the food that is nourishing the bacteria. Breast milk contains a certain set of bacteria linked to mom’s gut. Formula contains other, often more inflammatory types of bacteria.

Most of us are aware of the alteration in the gut microbiome associated with antibiotics, but as you know, there are many other factors out there that will disrupt the microbiome. Sometimes those disruptions are inevitable. We’re going to have to alter that gut microbiota, so what are the implications? Is that something that should factor into a decision whether or not to treat a child with an antimicrobial? Where does that leave us with probiotics? Is that something that should be initiated or not? Do we have the answers to those questions yet?

There are a number of studies showing hints of long-term problems with antibiotics. We know that in livestock, antibiotics have been used as growth promoters to help fatten up cattle more quickly. There are some suggestions that antibiotics could also produce obesity in kids.

Disruptions in microbiota may also be associated with autoimmune problems. One recent study this year found an association between antibiotic use and development of arthritis in kids.[13] We just have glimpses of what those connections may be and don’t know the full picture. But we do know that as many as 50%, maybe more, of the antibiotics that are given to children for respiratory conditions are not helpful.[14,15] It makes all the sense in the world to reserve antibiotics for when they are most useful and most necessary.

Clearly antibiotics have been one of the greatest discoveries and inventions in the history of humanity, but reserving them for situations where they’re most necessary only makes them more powerful and can help eliminate some of the unintended consequences we don’t even understand yet.

On the probiotic side, there’s also a lot we don’t know. There have been some studies going back more than 100 years showing that yogurt, for instance, led to improved health and longevity. There have been a number of placebo-controlled, double-blinded studies recently showing specific outcomes from specific strains in probacteria, improvement in things like the length of diarrhea, illness, symptoms of abdominal discomfort, eczema, and likelihood of getting respiratory infections including the flu.

But each of those also is a relatively tiny glimpse into the potential benefits of supporting and cultivating a diverse ecosystem within the gut. Probiotics may be helpful. It’s hard to say at this point which ones would be the best or how much. One thing that we can say is that eating a healthy diet is likely to select for bacteria that thrive on the healthy diet and would be a reinforcing virtuous circle. It would help you crave those foods more and help get the most benefit out of those foods.

Is Looking at Glycemic Index Valid?

Medscape: Are there any other recent studies that you would like to discuss?

Dr Greene: I think one very interesting 2015 study, published in November, looked at the glycemic index.[16] The idea behind the glycemic index is to measure the effect of a particular food or type of food on the subsequent blood glucose curve. Foods with a high glycemic index tend to raise blood sugar a lot. Low glycemic index foods have a much more muted effect on blood glucose. Glycemic index provides one way to look at why a food might be healthier or less healthy. You can find tables listing the glycemic index for a wide variety of foods.

In this study, the researchers measured about 50,000 different meals in 800 subjects and found something that in retrospect should have been obvious but was very surprising to me. The authors concluded that, to a large degree, individual foods do not have their own glycemic index. Rather, the glucose response to a particular food depends on the person. For instance, tomato is considered to be a very low glycemic index food, and yet for one subject in the study, tomatoes specifically prompted high blood glucose levels.

Data from a continuous blood glucose monitor worn by another individual demonstrated a glucose level that shot up to 260 mg/dL after a meal that included brown rice, which is reasonable from a glycemic index perspective. Different foods do, in fact, affect different people differently. We’re at the beginning of being able to figure out what that all means. It is probably a combination of an individual’s genetics and microbiome. Different foods really affect us differently, and the same great diet isn’t good for everyone.

References

  1. Ning H, Labarthe DR, Shay CM, et al. Status of cardiovascular health in US children up to 11 years of age: the National Health and Nutrition Examination Surveys 2003-2010. Circ Cardiovasc Qual Outcomes. 2015;8:164-171. Abstract
  2. Constantino MI, Molyneaux L, Limacher-Gisler F, et al. Long-term complications and mortality in young-onset diabetes: type 2 diabetes is more hazardous and lethal than type 1 diabetes. Diabetes Care. 2013;36:3863-3869. Abstract
  3. O’Connor L, Imamura F, Lentjes MA, Khaw KT, Wareham NJ, Forouhi NG. Prospective associations and population impact of sweet beverage intake and type 2 diabetes, and effects of substitutions with alternative beverages. Diabetologia. 2015;58:1474-1483. Abstract
  4. Yan J, Liu L, Zhu Y, Huang G, Wang PP. The association between breastfeeding and childhood obesity: a meta-analysis. BMC Public Health. 2014;14:1267.
  5. Cogswell ME, Yuan K, Gunn JP, et al. Vital signs: sodium intake among U.S. school-aged children – 2009-2010. MMWR Morb Mortal Wkly Rep. 2014;63:789-797. Abstract
  6. AAP Adolescent Sleep Working Group, Committee on Adolescence, and Council on School Health. School start times for adolescents. Pediatrics. 2014;134:642-649. http://pediatrics.aappublications.org/content/134/3/642 Accessed July 20, 2015.
  7. Andersson O, Hellström-Westas L, Andersson D, Domellöf M. Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months: a randomised controlled trial. BMJ. 2011;343:d7157.http://www.bmj.com/content/343/bmj.d7157 Accessed July 20, 2015.
  8. Andersson O, Lindquist B, Lindgren M, Stjernqvist K, Domellöf M, Hellström-Westas L. Effect of delayed cord clamping on neurodevelopment at 4 years of age: a randomized clinical trial. JAMA Pediatr. 2015;169:631-638.
  9. McDonagh MS, Blazina I, Dana T, Cantor A, Bougatsos C. Screening and routine supplementation for iron deficiency anemia: a systematic review. Pediatrics. 2015;135:723-733. Abstract
  10. US Preventive Services Task Force. Iron deficiency anemia in young children: screening.http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/iron-deficiency-anemia-in-young-children-screening Accessed January 4, 2016.
  11. McDonald SJ, Middleton P, Dowswell T, Morris PS. Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes. Cochrane Database Syst Rev. 2013;7:CD004074.http://www.cochrane.org/CD004074/PREG_effect-timing-umbilical-cord-clamping-term-infants-mother-and-baby-outcomesAccessed January 4, 2016.
  12. Baker RD, Greer FR; American Academy of Pediatrics, Committee on Nutrition. Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age). Pediatrics. 2010;126:1040-1050. Abstract
  13. Horton DB, Scott FI, Haynes K, et al. Antibiotic exposure and juvenile idiopathic arthritis: a case-control study. Pediatrics. 2015;136:e333-e343. Abstract
  14. Centre for Clinical Practice at NICE (UK). Respiratory Tract Infections – Antibiotic Prescribing. NICE Clinical Guidelines, No. 69. July 2008. http://www.ncbi.nlm.nih.gov/books/NBK53632/ Accessed January 4, 2016.
  15. Kronman MP, Zhou C, Mangione-Smith R. Bacterial prevalence and antimicrobial prescribing trends for acute respiratory tract infections. Pediatrics. 2014;134:e956-e965. Abstract
  16. Zeevi D, Korem T, Zmora N, et al. Personalized nutrition by prediction of glycemic responses. Cell. 2015;163:1079-1094.Abstract

 

Learn More +
Diabetes Research Connection Logo

Scientists Identify Factor That May Trigger Type 1 Diabetes

Original article provided by University of Colorado Denver on February 11, 2016. Click here to read the original article.

A team of researchers, led by investigators at the University of Colorado School of Medicine, have identified a new class of antigens that may be a contributing factor to type 1 diabetes, according to an article published in the current issue of the journal Science.

In autoimmune disease, the key question is why the immune system attacks the body’s own tissues. Type 1 diabetes is the autoimmune form of diabetes, in which insulin-producing beta cells in the pancreas are destroyed by immune cells, especially those known as T cells. Insulin is the hormone that regulates levels of glucose in the blood and without insulin, a life-threatening disease results. Currently, there is no cure for type 1 diabetes.

“Our lab studies the type of T cell known as a CD4 T cell,” said Kathryn Haskins, PhD, professor of immunology and microbiology and corresponding author of the article. “We have focused on autoreactive CD4 T cells using a mouse model of autoimmune diabetes. We have been especially interested in identifying the antigens that activate these T cells.”

Antigens for T cells are pieces of proteins, or protein fragments (peptides) that have to be taken up and presented to the T cells by antigen-presenting cells. Normally, a CD4 T cell is supposed to respond to “foreign” antigens, like a viral peptide. But in autoimmune disease the T cells respond to antigens that are generated in the body. Such proteins and peptides are called autoantigens.

When an autoreactive T cell sees its antigen, it becomes activated and can initiate disease. By identifying those antigens, scientists may be able to use that information to detect autoreactive T cells early in disease, or better yet, in at-risk individuals. If they are able to use the antigens to turn off destructive T cells, they may be able to prevent the disease.

Haskins and others, including fellow corresponding author Thomas Delong, PhD, assistant professor of immunology and microbiology, conducted experiments to analyze the fractions of beta cells that contain antigen for autoreactive CD4 T cells in order to identify autoantigens in type 1 diabetes. They discovered a new class of antigens that consist of insulin fragments fused to peptides of other proteins present in beta cells. That fusion leads to generation of hybrid insulin peptides that are not encoded in an individual’s genome.

If peptides in the body are modified from their original form, they essentially become “foreign” to the immune system and this may explain why they become targets for the autoreactive T cells. The discovery of hybrid peptides as targets of the immune system provides a plausible explanation of how the immune system is tricked into destroying the body’s own beta cells. The discovery may also lead to a better understanding of other autoimmune diseases.

More Information: “Pathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion,” by T. Delong et al. science.sciencemag.org/cgi/doi/10.1126/science.aad2791

Learn More +
MIT-Diabetes-Stem-1_0

No More Insulin Injections?

Original article written by Anne Trafton for MIT News Office on January 26, 2016. Click here to read the original article.

MIT-Diabetes-Stem-1_0
A stealth material surface, shown here, has been engineered to provide an “invisibility cloak” against the body’s immune system cells. In this electron microscopy image, you can see the material’s surface topography.
Courtesy of the researchers.

In patients suffering from Type 1 diabetes, the immune system attacks the pancreas, eventually leaving patients without the ability to naturally control blood sugar. These patients must carefully monitor the amount of sugar in their blood, measuring it several times a day and then injecting themselves with insulin to keep their blood sugar levels within a healthy range. However, precise control of blood sugar is difficult to achieve, and patients face a range of long-term medical problems as a result.

A better diabetes treatment, many researchers believe, would be to replace patients’ destroyed pancreatic islet cells with healthy cells that could take over glucose monitoring and insulin release. This approach has been used in hundreds of patients, but it has one major drawback — the patients’ immune systems attack the transplanted cells, requiring patients to take immunosuppressant drugs for the rest of their lives.

MIT-Diabetes-Stem-2
Glucose-stimulated insulin-producing cells, derived from stem cells, are protected inside capsules that are engineered to be invisible to the host immune system.
Courtesy of the researchers.

Now, a new advance from MIT, Boston Children’s Hospital, and several other institutions may offer a way to fulfill the promise of islet cell transplantation. The researchers have designed a material that can be used to encapsulate human islet cells before transplanting them. In tests on mice, they showed that these encapsulated human cells could cure diabetes for up to six months, without provoking an immune response.

Although more studies are needed, this approach “has the potential to provide diabetics with a new pancreas that is protected from the immune system, which would allow them to control their blood sugar without taking drugs. That’s the dream,” says Daniel Anderson, the Samuel A. Goldblith Associate Professor in MIT’s Department of Chemical Engineering, a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES), and a research fellow in the Department of Anesthesiology at Boston Children’s Hospital.

Anderson is the senior author of two studies describing this method in the Jan. 25 issues ofNature Medicine and Nature Biotechnology. Researchers from Harvard University, the University of Illinois at Chicago, the Joslin Diabetes Center, and the University of Massachusetts Medical School also contributed to the research.

MIT-Diabetes-Stem-3
Glucose-stimulated insulin-producing cells derived from stem cells.
Courtesy of the researchers.

Encapsulating cells

Since the 1980s, a standard treatment for diabetic patients has been injections of insulin produced by genetically engineered bacteria. While effective, this type of treatment requires great effort by the patient and can generate large swings in blood sugar levels.

At the urging of JDRF director Julia Greenstein, Anderson, Langer, and colleagues set out several years ago to come up with a way to make encapsulated islet cell transplantation a viable therapeutic approach. They began by exploring chemical derivatives of alginate, a material originally isolated from brown algae. Alginate gels can be made to encapsulate cells without harming them, and also allow molecules such as sugar and proteins to move through, making it possible for cells inside to sense and respond to biological signals.

However, previous research has shown that when alginate capsules are implanted in primates and humans, scar tissue eventually builds up around the capsules, making the devices ineffective. The MIT/Children’s Hospital team decided to try to modify alginate to make it less likely to provoke this kind of immune response.

“We decided to take an approach where you cast a very wide net and see what you can catch,” says Arturo Vegas, a former MIT and Boston Children’s Hospital postdoc who is now an assistant professor at Boston University. Vegas is the first author of the Nature Biotechnology paper and co-first author of the Nature Medicine paper. “We made all these derivatives of alginate by attaching different small molecules to the polymer chain, in hopes that these small molecule modifications would somehow give it the ability to prevent recognition by the immune system.”

After creating a library of nearly 800 alginate derivatives, the researchers performed several rounds of tests in mice and nonhuman primates. One of the best of those, known as triazole-thiomorpholine dioxide (TMTD), they decided to study further in tests of diabetic mice. They chose a strain of mice with a strong immune system and implanted human islet cells encapsulated in TMTD into a region of the abdominal cavity known as the intraperitoneal space.

The pancreatic islet cells used in this study were generated from human stem cells using a technique recently developed by Douglas Melton, a professor at Harvard University who is an author of the Nature Medicine paper.

Following implantation, the cells immediately began producing insulin in response to blood sugar levels and were able to keep blood sugar under control for the length of the study, 174 days.

“The really exciting part of this was being able to show, in an immune-competent mouse, that when encapsulated these cells do survive for a long period of time, at least six months,” says Omid Veiseh, a senior postdoc at the Koch Institute and Boston Children’s hospital, co-first author of the Nature Medicine paper, and an author of the Nature Biotechnology paper. “The cells can sense glucose and secrete insulin in a controlled manner, alleviating the mice’s need for injected insulin.”

The researchers also found that 1.5-millimeter diameter capsules made from their best materials (but not carrying islet cells) could be implanted into the intraperitoneal space of nonhuman primates for at least six months without scar tissue building up.

“The combined results from these two papers suggests that these capsules have real potential to protect transplanted cells in human patients,” says Robert Langer, the David H. Koch Institute Professor at MIT, a senior research associate at Boston’s Children Hospital, and co-author on both papers.  “We are so pleased to see this research in cell transplantation reach these important milestones.”

Cherie Stabler, an associate professor of biomedical engineering at the University of Florida, says this approach is impressive because it tackles all aspects of the problem of islet cell delivery, including finding a source of cells, preventing an immune response, and developing a suitable delivery material.

“It’s such a complex, multipronged problem that it’s important to get people from different disciplines to address it,” says Stabler, who was not involved in the research. “This is a great first step towards a clinically relevant, cell-based therapy for Type I diabetes.”

Insulin independence

The researchers now plan to further test their new materials in nonhuman primates, with the goal of eventually performing clinical trials in diabetic patients. If successful, this approach could provide long-term blood sugar control for such patients. “Our goal is to continue to work hard to translate these promising results into a therapy that can help people,” Anderson says.

“Being insulin-independent is the goal,” Vegas says. “This would be a state-of-the-art way of doing that, better than any other technology could. Cells are able to detect glucose and release insulin far better than any piece of technology we’ve been able to develop.”

The researchers are also investigating why their new material works so well. They found that the best-performing materials were all modified with molecules containing a triazole group — a ring containing two carbon atoms and three nitrogen atoms. They suspect this class of molecules may interfere with the immune system’s ability to recognize the material as foreign.

The work was supported, in part, by the JDRF, the Leona M. and Harry B. Helmsley Charitable Trust, the National Institutes of Health, and the Tayebati Family Foundation.

Other authors of the papers include MIT postdoc Joshua Doloff; former MIT postdocs Minglin Ma and Kaitlin Bratlie; MIT graduate students Hok Hei Tam and Andrew Bader; Jeffrey Millman, an associate professor at Washington University School of Medicine; Mads Gürtler, a former Harvard graduate student; Matt Bochenek, a graduate student at the University of Illinois at Chicago; Dale Greiner, a professor of medicine at the University of Massachusetts Medical School; Jose Oberholzer, an associate professor at the University of Illinois at Chicago; and Gordon Weir, a professor of medicine at the Joslin Diabetes Center.

Learn More +
Insulin-Producing Pancreatic Cells

Insulin-Producing Pancreatic Cells Created from Human Skin Cells

Original article written by Dana Smith for Gladstone Institutes on January 6, 2016. Click here to read the original article.

SAN FRANCISCO, CA—Scientists at the Gladstone Institutes and the University of California, San Francisco (UCSF) have successfully converted human skin cells into fully-functional pancreatic cells. The new cells produced insulin in response to changes in glucose levels, and, when transplanted into mice, the cells protected the animals from developing diabetes in a mouse model of the disease.

The new study, published in Nature Communications, also presents significant advancements in cellular reprogramming technology, which will allow scientists to efficiently scale up pancreatic cell production and manufacture trillions of the target cells in a step-wise, controlled manner. This accomplishment opens the door for disease modeling and drug screening and brings personalized cell therapy a step closer for patients with diabetes.

Pancreatic cells

Functioning human pancreatic cells after they’ve been transplanted into a mouse. [Image: Saiyong Zhu]

“Our results demonstrate for the first time that human adult skin cells can be used to efficiently and rapidly generate functional pancreatic cells that behave similar to human beta cells,” says Matthias Hebrok, PhD, director of the Diabetes Center at UCSF and a co-senior author on the study. “This finding opens up the opportunity for the analysis of patient-specific pancreatic beta cell properties and the optimization of cell therapy approaches.”

In the study, the scientists first used pharmaceutical and genetic molecules to reprogram skin cells into endoderm progenitor cells—early developmental cells that have already been designated to mature into one of a number of different types of organs. With this method, the cells don’t have to be taken all the way back to a pluripotent stem cell state, meaning the scientists can turn them into pancreatic cells faster. The researchers have used a similar procedure previously to create heart, brain, and liver cells.

After another four molecules were added, the endoderm cells divided rapidly, allowing more than a trillion-fold expansion. Critically, the cells did not display any evidence of tumor formation, and they maintained their identity as early organ-specific cells.

The scientists then progressed these endoderm cells two more steps, first into pancreatic precursor cells, and then into fully-functional pancreatic beta cells. Most importantly, these cells protected mice from developing diabetes in a model of disease, having the critical ability to produce insulin in response to changes in glucose levels.

“This study represents the first successful creation of human insulin-producing pancreatic beta cells using a direct cellular reprogramming method,” says first author Saiyong Zhu, PhD, a postdoctoral researcher at the Gladstone Institute of Cardiovascular Disease. “The final step was the most unique—and the most difficult—as molecules had not previously been identified that could take reprogrammed cells the final step to functional pancreatic cells in a dish.”

Sheng Ding, PhD, a senior investigator in the Roddenberry Stem Cell Center at Gladstone and co-senior author on the study, adds, “This new cellular reprogramming and expansion paradigm is more sustainable and scalable than previous methods. Using this approach, cell production can be massively increased while maintaining quality control at multiple steps. This development ensures much greater regulation in the manufacturing process of new cells. Now we can generate virtually unlimited numbers of patient-matched insulin-producing pancreatic cells.”

Holger Russ, PhD, was a co-first author on the paper from UCSF. Other Gladstone investigators include Xiajing Wang, Mingliang Zhang, Tianhua Ma, Tao Xu, and Shibing Tang. Funding was provided by the Roddenberry Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, National Eye Institute, National Institute of Child Health and Human Development, National Institute of Mental Health, California Institute of Regenerative Medicine, Prostate Cancer Foundation, and the Leona M. & Harry B. Helmsley Charitable Trust.

About the Gladstone Institutes

To ensure our work does the greatest good, the Gladstone Institutes focuses on conditions with profound medical, economic, and social impact—unsolved diseases of the brain, the heart, and the immune system. Affiliated with the University of California, San Francisco, Gladstone is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease.

Contact Person

Dana Smith
Direct line: 415.734.2532
Mobile: 415.806.6245

Learn More +

Prevalence of Diabetes and Diabetic Nephropathy in a Large U.S. Commercially Insured Pediatric Population, 2002–2013

Original article written by Lin Li, Susan Jick, Stefanie Breitenstein, and Alexander Michel for The Diabetes Journal on August 3, 2015. Click here to read the original article.

Abstract

DiabetesJournalOBJECTIVE To estimate the prevalence of diabetes and diabetic nephropathy in a large population of U.S. commercially insured patients aged <18 years from 2002 to 2013.

 

RESEARCH DESIGN AND METHODS Using the U.S. MarketScan commercial claims database, we identified 96,171 pediatric patients with diabetes and 3,161 pediatric patients with diabetic nephropathy during 2002–2013. We estimated prevalence of pediatric diabetes overall; by diabetes type, age, and sex; and prevalence of pediatric diabetic nephropathy overall; by age, sex, and diabetes type.

 

RESULTS The annual prevalence of diabetes in the whole pediatric population increased from 1.86 to 2.82 per 1,000 during 2002–2013: 1.48 to 2.32 per 1,000 for type 1 diabetes and 0.38 to 0.67 per 1,000 for type 2 diabetes in 2002–2006 and then 0.56 to 0.49 per 1,000 thereafter. The annual prevalence of diabetic nephropathy in pediatric patients with diabetes increased from 1.16 to 3.44% for all cases and 0.83 to 2.32% for probable cases only in 2002–2013. Prevalence of diabetes and diabetic nephropathy was highest in patients aged 12 to <18 years. While prevalence of type 1 diabetes was higher in male than in female youth, prevalence of type 2 diabetes and diabetic nephropathy was higher in female than in male youth. There was no difference in prevalence of diabetic nephropathy by diabetes type.

 

CONCLUSIONS The prevalence of diabetes and diabetic nephropathy increased in the U.S. MarketScan commercially insured pediatric population from 2002 to 2013. The prevalence of diabetes and diabetic nephropathy markedly increased starting at age 12 years.

Learn More +

New Type 4 Diabetes Not Linked To Obesity

DRC-12.29Image
The Salk Institute’s Ron Evans explains how immune cell dysfunction can lead to diabetes. -Salk Institute

Original article written by Bradley J. Fikes for The San Diego Union Tribune on November 18, 2015. Click here to read the original article.

A new type of diabetes that’s not associated with insulin deficiency or obesity has been discovered — in mice.

In a study published Wednesday, researchers led by Salk Institute scientists found that in a mouse model of the disease regarded as predictive of human diabetes, some develop an unusual type that affects old, lean mice.

This disease is caused by overactivity of a certain kind of immune system cell. The researchers call this new form Type 4 diabetes.

The study was published in the journal Nature. Go to j.mp/type4diabetes for the study.

If the study is confirmed in people — a big if — the public health implications would be profound. Diabetes can lead to blindness, kidney and heart disease, and poor blood circulation that can lead to amputation. Diabetes is usually associated with obesity, and a form that is not may escape detection because doctors aren’t looking for it.

The study was led by the Salk’s Ronald Evans and Ye Zheng. Evans said it’s possible that millions of Americans have this type of diabetes.

“Oftentimes people think that if they’re lean, they’re protected from diabetes, and most physicians would think that,” Evans said.

The researchers envision a potential treatment by developing an antibody drug to reduce levels of these overactive immune cells. That will take at least a few years, Evans said.

Evans estimates that about 20 percent of diabetics over 65 have this newly identified version, and may not be getting the proper care. More than 9.4 million diabetic Americans are over 65 as of 2012, according to the Kaiser Family Foundation. And that number doesn’t count those who haven’t been diagnosed.

So the total number of Americans with this new type of diabetes could reach about 2 million, if Evans’ estimate is accurate.

Evans said treatment of lean, elderly diabetics is less effective, because it’s largely focused on reducing consumption of fat or losing weight, which isn’t a factor for these people. Some of the regular diabetes drugs, such as the standby metformin, show some effectiveness, Evans said. Metformin is a good choice because it’s safe.

But even with the many drugs on the market, more are needed.

“Diabetes in general is not a well-managed disease,” Evans said.

Confirmation needed

Announcing a new form of diabetes is a bit premature, said UC San Diego diabetes researcher Alan Saltiel, who was not involved in the study. Confirmation in humans still needs to be done. That means finding evidence in old, lean people of overactivity of these immune cells, called T regulatory cells, Saltiel said. These “Treg” cells suppress inflammation and tamp down the immune response.

Saltiel, who co-authored an accompanying commentary in Nature, said that despite his caution, the study is significant. It indicates that the story of diabetes is much more complicated than previously thought. Suppressing inflammation was supposed to be a good thing, but this study indicates it’s not always the case.

“It’s very surprising,” Saltiel said. “We didn’t expect these Treg cells to play this role. It’s been assumed that diabetes is kind of an inflammatory disease, that obesity begets inflammation, and then inflammation plays a big role in the generation of diabetes.”

While no animal model equals evidence from humans, Saltiel said the mouse model tested in the study is the best one around. But while it’s accurate in imitating many aspects of human diabetes, he cautioned that it’s not perfect in mimicking what diabetes does in people.

Another expert, Scripps Health clinical endocrinologist Athena Philis-Tsimikas, said the findings make sense.

“Clinically we see a wide variety of patient ‘types’ and body habitus that all have similar rises in blood sugar,” she said by email. “The variation is found in individuals that are older, younger, lean, overweight and different racial/ethnic mix. So the findings in this article are definitely interesting and it would seem logical that with so many clinical pictures that there must be different underlying mechanisms such as those described in this article.”

“One exciting outcome of studies like these are that with so many new therapies in diabetes that the discovery of new mechanisms may allow us to tailor a more unique therapeutic regimen for our individual patients,” Philis-Tsimikas said. “I find this kind of work very exciting and look forward to seeing further work in humans.”

Balancing act

All forms of diabetes involve abnormally high levels of blood sugar. This is mainly regulated by two hormones. Insulin lowers blood sugar levels, and glucagon raises them. With this brake and accelerator system, blood sugar levels can be controlled within a narrow range.

Type 1 diabetes is caused by a lack of insulin, and eventually is fatal unless insulin is provided. It’s caused by an autoimmune reaction that destroys the insulin-producing islet cells in the pancreas. Inflammation is believed to be part of the autoimmune response.

Type 2 diabetes, by far the most common, is caused by resistance to insulin. This requires production of larger amounts of insulin to overcome the resistance and drive down blood sugar levels. It’s related to being overweight and obese. Inflammation produced by other immune cells called macrophages drives obesity-associated insulin resistance, which may be a sign of pre-diabetes.

More tentatively, a third type of diabetes has recently been proposed. It’s called Type 3 diabetes and is associated with Alzheimer’s. It’s thought to be caused by the effects of diabetes on the brain.

A fourth type of diabetes, caused by suppressing inflammation, would add another layer of complexity, Saltiel said.

“People have looked at Tregs in obesity, and the idea was that they were protective, that they were lost in the obese state,” Saltiel said. “What this paper is saying that surprisingly, they’re going up in aging, and aging is another condition associated with resistance to insulin.”

More tentatively, a third type of diabetes has recently been proposed. It’s called type 3 diabetes and is associated with Alzheimer’s. It’s thought to be caused by the effects of diabetes on the brain.

A fourth type of diabetes would add another layer of complexity, Saltiel said.

“People have looked at Tregs in obesity, and the idea was that they were protective, that they were lost in the obese state,” Saltiel said. “What this paper is saying that surprisingly, they’re going up in aging, and aging is another condition associated with resistance to insulin.”

Learn More +
Diabetes Shot

End of Daily Injections for Diabetes as Scientists Restore Insulin Production

Diabetes Shot
In future people with diabetes may not need to inject themselves on a daily basis. Photo: Alamy

Original article written by Sarah Knapto, Science Editor, for The Telegraph on November 25, 2015. Click here to read the original article.

The end of daily injections for diabetes sufferers could be in sight after scientists showed it is possible to restore insulin production for up to a year by boosting the immune system.

Hundreds of thousands of people in Britain suffer from Type 1 diabetes and need to inject themselves daily to keep blood sugar levels under control.

The disease attacks insulin-secreting cells in the pancreas. Healthy people have billions of ‘peacekeeping’ cells called ‘T-regs’ which protect insulin-making cells from the immune system but people suffering Type 1 diabetes do not have enough.

“The T-reg intervention frees people like me from the daily grind of insulin therapy and lifelong fear of complication” – Mary Rooney, Type 1 diabetes patient

Now researchers at the University of California and Yale have shown that the ‘T-regs’ can be removed from the body, increased by 1,500x in the laboratory and infused back into the bloodstream to restore normal function.

An initial trial of 14 people has shown that the therapy is safe, and can last up to a year.

“This could be a game-changer,” said Dr Jeffrey Bluestone, Professor in Metabolism and Endocrinology at the University of California, San Francisco (UCSF).

“By using T-regs to ‘re-educate’ the immune system, we may be able to really change the course of this disease.

“We expect T-regs to be an important part of diabetes therapy in the future.”

Insulin Shot
Sufferes of type 1 and type 2 diabetes may have to inject insulin daily  Photo: Alamy

Not only does the treatment stop the need for regular insulin injections, but it prevents the disease progressing which could save sufferers from blindness and amputation in later life.

Diabetes is an autoimmune disease. The immune system usually defends against infections, but in Type 1 diabetes the process goes awry and as well as fighting foreign invaders, it also targets the body’s own cells.

In the new procedure, doctors removed around two cups of blood containing around two to four million ‘T-reg’ cells from 14 patients aged between 18 and 43 who had been recently diagnosed with diabetes. Their ‘T-reg’ cells were separated from other cells and replicated in a growth medium, before being infused back into the blood.

Child psychologist Mary Rooney, 39, who was diagnosed with type diabetes in 2011, was the first trial participant, and said the therapy had ‘freed her from the daily grind’ of injections.

Speaking of her diagnosis she said: “After weeks of losing weight, always being thirsty, having blurry vision that would come and go, and generally feeling run-down, I knew something wasn’t right. Type 1 diabetes was the furthest from my mind, though.

“Initially, I was in a state of shock. I didn’t realize that you could be diagnosed with Type 1 diabetes as an adult

“My first thoughts were “This sucks” and “This can’t possibly be happening,” but I knew I couldn’t just stay in a state of denial and disappointment forever.”

Miss Rooney, who worked as a researcher at the University of California soon learned that the institution was looking for patients for the T-reg trial, and asked to be enrolled.

“By being that first patient, I knew I was taking a chance. And I have to be honest: I was scared,” she added.

“But I liked the fact that this experimental treatment involved using my own regulatory T-cells, which would be expanded in a lab and then re-infused. The theory behind this study really made sense to me.

“The T-reg intervention frees people like me from the daily grind of insulin therapy and lifelong fear of complication.”

The team say that T-Reg treatments also hold promise as treatments for other autoimmune diseases such as rheumatoid arthritis and lupus, and even as therapies for cardiovascular disease, neurological diseases and obesity.

The research was published in the journal Science Translational Medicine.

Learn More +

Can Eye Screening for Diabetic Kids Be Delayed a Bit?

Original article written by Robert Preidt via HealthDay News on September 9, 2015. Click here to read the original article.

Children with type 1 diabetes may not need to start screening for eye disease as early as currently recommended, a new study suggests.Can Eye Screening for Diabetic Kids Be Delayed a Bit?

Most children with type 1 diabetes probably don’t need a yearly exam for diabetes-related eye disease (diabetic retinopathy) until age 15, or 5 years after their diabetes diagnosis, whichever is later, the study authors reported online Sept. 1 in the journal Ophthalmology.

“Many of our young patients with diabetes diligently come in every year for screenings that consistently show no sign of the disease,” study co-author Dr. Gil Binenbaum, attending surgeon in the ophthalmology division at The Children’s Hospital of Philadelphia, said in a journal news release.

“Of course, that’s good news for them, and it is very important to have annual eye exams once the risk of vision loss develops. But, is it worth the burden on the family and the health care system if evidence shows that diabetic retinopathy doesn’t reach a treatable stage until years later?”

Early detection and treatment of diabetic retinopathy reduces vision loss in adults, the researchers said. Some medical groups currently recommend that screening start at age 9, or three to five years after a type 1 diabetes diagnosis.

But, this study found no evidence of diabetic retinopathy in 370 children who had at least one screening. And, that was true regardless of how long they had diabetes. It was also true whether their blood sugar levels were well controlled or not, the research showed. The children were all 18 or younger, and had type 1 or type 2 diabetes.

Children with type 2 diabetes and those at high risk for diabetic complications should begin screening as soon as they are diagnosed with diabetes, the study authors said. Many people with type 2 diabetes live with uncontrolled disease before they are diagnosed, the researchers explained.

Diabetic retinopathy is the leading cause of blindness among working-age Americans, according to the U.S. National Eye Institute (NEI). The eye disease affects nearly 8 million people in the United States, the NEI said.

More information

The U.S. National Eye Institute has more about diabetic retinopathy.

SOURCE: Ophthalmology, news release, Sept. 1, 2015

Learn More +

Drug Prevents Type 1 Diabetes In Mice

Original article written by Bruce Goldman via Stanford Medical on September 14, 2015. Click here to read the original article.

A compound that blocks the synthesis of hyaluronan, a substance generally found in in all body tissue, protected mice from getting type 1 diabetes. The compound is already approved in Europe and Asia for the treatment of gallbladder disease.

The buildup of a substance in the pancreas during the pre-symptomatic stage of Type 1 diabetes is essential to the development of the disease, Stanford University School of Medicine researchers have shown.

Nadine Nagy and Paul Bollyky and their colleagues found that a drug helped prevent the onset of Type 1 diabetes in mice. They hope to find out if the drug will work similarly in humans. Norbert von der Groeben
Nadine Nagy and Paul Bollyky and their colleagues found that a drug helped prevent the onset of Type 1 diabetes in mice. They hope to find out if the drug will work similarly in humans. Norbert von der Groeben

The investigators used a drug to block production of this substance in mouse models, staving off damage to insulin-producing cells and preventing the onset of the autoimmune disorder. The drug, which is currently used in Europe and Asia for treating gallstone-related spasms, has an excellent safety record, the researchers said.

The findings, described in a study published online Sept. 14 in the Journal of Clinical Investigation, suggest that it may be possible to prevent the onset of Type 1 diabetes in humans if a similar treatment is initiated before the insulin-producing cells, or beta cells, are attacked by misguided immune cells. Type 1 diabetes, formerly called juvenile diabetes, afflicts one in 300 people in the United States.

The study is the first to link the progression of Type 1 diabetes to changes in the architecture of the extracellular matrix, the carbohydrate- and protein-rich lattice in which the cells composing our tissues are embedded, said Paul Bollyky, MD, PhD, assistant professor of infectious diseases. Bollyky is the study’s senior author. The lead author is postdoctoral scholar Nadine Nagy, PhD.

Most pancreatic cells are engaged in manufacturing and secreting digestive enzymes. But the pancreas is also studded with tiny, hormone-producing cell clusters called islets. A human pancreas contains thousands of islets, scattered throughout the organ like raisins in a loaf of cinnamon bread.

Inflamed islets

A pancreatic islet is composed of several cell types, each making a different hormone. Beta cells, for example, produce insulin.

“In Type 1 diabetes, only the beta cells get destroyed,” said Bollyky. Why this happens is poorly understood. But it’s known that during the disorder’s early, pre-symptomatic stage, pancreatic islets become inflamed — that is, they get infiltrated by immune cells. At first quiescent, these warrior cells at some point begin attacking beta cells, eventually destroying enough of them to effectively erase insulin output. By the time a person begins to manifest the disease’s hallmark symptom, chronic hyperglycemia, some 90 percent of pancreatic beta cells have been killed off. Neither the cause of immune cells’ initial infiltration of pancreatic islets nor the trigger for their transition from mere passive presence to active aggression is yet understood.

But the new study provides important clues.

In a 2014 study, Bollyky’s team measured the levels of dozens of substances in the extracellular matrix of human postmortem pancreatic tissue. One substance, called hyaluronan, was overly abundant near the pancreatic beta cells of people with Type 1 diabetes. But this was seen only in pancreatic tissue from patients who had been somewhat recently diagnosed, not patients who’d lived with the disease for decades.

9.22Quote1Hyaluronan is usually present at trace concentrations in the extracellular matrix that pervades all tissues. But hyaluronan levels spike markedly at the site of an injury. “If you twist your ankle or stub your toe, that swelling you see afterwards is due to hyaluronan,” Bollyky said. This substance is prone to soaking up water, causing fluid buildup in the injured region, a cardinal feature of inflammation.

Bollyky said the absence of increased hyaluronan in long-term patients’ pancreatic islets didn’t mean much, as these people’s beta cells had long since bit the dust. But finding excessive deposits of hyaluronan near pancreatic beta cells in recent-onset cases was intriguing.

Curious, Bollyky and his colleagues sought to determine whether this association was incidental or whether hyaluronan’s increased presence actually played any causal role. So, they employed a bioengineered strain of laboratory mouse whose immune system is guaranteed to attack its pancreatic beta cells. Essentially 100 percent of these mice eventually develop Type 1 diabetes, and always over about the same period of time, making it easy to study the effects of an experimental manipulation upon the disease’s progression.

The scientists also looked at another mouse strain often afflicted with a version of Type 1 diabetes that more closely parallels the human form of the disease. (These mice are tougher to study because only about half of them contract the disease, and they do so at variable rates.)

In both strains, Bollyky said, hyaluronan accumulated in pancreatic islets, but not in all of them — just in those where inflammatory immune cells had parked themselves. No excessive hyaluronan deposition was seen in the mice’s heart, lung or liver tissue, consistent with the idea that the phenomenon occurs only in inflamed tissues. The islet-associated hyaluronan buildup eventually crescendoed and began tapering off, analogous to the investigators’ observations in recent-onset versus long-established Type 1 diabetes cases in their earlier study of human tissue.

Preventing hyaluronan buildup

“We wondered what would happen if we prevented that buildup,” Bollyky said. “And we knew a drug that does that.” The drug was hymecromone, or 4-methylumbelliferone (4-MU for short). Prescribed in many European and Asian countries for painful, gallstone-associated spasms and sold by about 60 companies worldwide for research purposes, 4-MU inhibits hyaluronan synthesis. It is inexpensive, can be given orally and, over four decades of use, has what Bollyky described as an “extremely boring safety profile”: a very low rate of associated adverse events. “It’s even approved in Europe for kids,” he said. (The Food and Drug Administration has not licensed 4-MU for any indication in the United States.)

In the mice used in the study, as in people, there’s a window of time during which immune cells have infiltrated pancreatic islets but most beta cells are still intact. When the researchers initiated 4-MU treatment before the majority of the mice’s beta cells had been wiped out, none of the mice developed hyperglycemia. Mice that didn’t get 4-MU did. If mice stayed on a 4-MU regimen, they remained diabetes-free for at least a year. But if the regimen was stopped, they quickly became diabetic.

9.22Quote2Tissue analysis revealed the continued presence of immune cells situated close to beta cells even in mice getting 4-MU, but the beta cells themselves seemed normal; the immune cells had evidently refrained from attacking them. The scientists also found reduced hyaluronan levels in 4-MU-treated mice’s pancreatic islets, indicating that the drug was performing as expected.

Further experiments in the mice showed that hyaluronan prevents the induction of a class of regulatory immune cells, known as Tregs, whose job is to rein in their aggressive fellow immune cells and keep them from damaging healthy tissue. Bollyky likened Tregs’ function to that of military police. In the absence of appropriate supervision, immune cells can get trigger-happy, he said. But by impeding hyaluronan synthesis, 4-MU re-establishes the induction of enough Tregs to prevent beta-cell destruction.

No drug has previously been shown to do this in humans, Bollyky said. His group has received preliminary funding from SPARK, a Stanford-based program devoted to fostering drug-development entrepreneurship, and is working with the FDA in preparation for a clinical trial of 4-MU for preventing Type 1 diabetes. The Stanford Office of Technology Licensing has applied for a use patent on associated intellectual property.

The study was performed in collaboration with scientists at the Benaroya Research Institute under the direction of matrix biologist Thomas Wight, PhD, whose group Bollyky was associated with when the work began. Funding for the study came from the Juvenile Diabetes Research Foundation and the National Institutes of Health (grants R01DK096087-01, R01HL113294 and U01AI101984).

Other Stanford-affiliated co-authors are postdoctoral scholar Vivekananda Sunkari, PhD, and basic life science research associates Gernot Kaber, PhD, and Hedwich Kuipers, PhD.

Stanford’s Department of Medicine also supported the work.

Learn More +

Prolonged Antibiotic Treatment Induces A Diabetogenic Intestinal Microbiome That Accelerates Diabetes In NOD Mice

gut-microbiomeOriginal article published by the ISME Journal on August 14, 2015. Click here to read the original article.

Accumulating evidence supports that the intestinal microbiome is involved in Type 1 diabetes (T1D) pathogenesis through the gut-pancreas nexus. Our aim was to determine whether the intestinal microbiota in the non-obese diabetic (NOD) mouse model played a role in T1D through the gut.

To examine the effect of the intestinal microbiota on T1D onset, we manipulated gut microbes by: (1) the fecal transplantation between non-obese diabetic (NOD) and resistant (NOR) mice and (2) the oral antibiotic and probiotic treatment of NOD mice. We monitored diabetes onset, quantified CD4+T cells in the Peyer’s patches, profiled the microbiome and measured fecal short-chain fatty acids (SCFA). The gut microbiota from NOD mice harbored more pathobionts and fewer beneficial microbes in comparison with NOR mice.

Fecal transplantation of NOD microbes induced insulitis in NOR hosts suggesting that the NOD microbiome is diabetogenic. Moreover, antibiotic exposure accelerated diabetes onset in NOD mice accompanied by increased T-helper type 1 (Th1) and reduced Th17 cells in the intestinal lymphoid tissues. The diabetogenic microbiome was characterized by a metagenome altered in several metabolic gene clusters. Furthermore, diabetes susceptibility correlated with reduced fecal SCFAs.

In an attempt to correct the diabetogenic microbiome, we administered VLS#3 probiotics to NOD mice but found that VSL#3 colonized the intestine poorly and did not delay diabetes. We conclude that NOD mice harbor gut microbes that induce diabetes and that their diabetogenic microbiome can be amplified early in life through antibiotic exposure. Protective microbes like VSL#3 are insufficient to overcome the effects of a diabetogenic microbiome.

Learn More +

Bacteria That Prevents Type 1 Diabetes

Original article published by Inserm on May 8, 2015. Click here to read the original article.

Our bodies have ten times the amount of microbes than human cells. This set of bacteria is called microbiota. In some instances, bacteria known as pathogens can cause infectious diseases. However, these micro-organisms can also protect us from certain diseases. Researchers from Inserm, Paris Descartes University and the CNRS (French National Centre for Scientific Research), through collaboration with teams from China and Sweden, have recently shown how microbiota protects against the development of type 1 diabetes. This research is published in the Immunity journal, 4 August 2015.

DIAB7TE
A pancreatic islet of Langerhans expressing the immunoregulator antimicrobial peptide CRAM (in red). The insulin-producting beta-cells are in green and the glucagon-producting alpha-cells are in blue. © Julien Diana

To combat pathogens, the immune system has developed various mechanisms to detect, defend against and even destroy micro-organisms that are harmful to the body. This includes antimicrobial peptides and natural proteins that destroy pathogenic bacteria by disrupting their cellular membrane. Not only are they produced by immune cells, they are also produced by cells whose functions are not immune-related.

A research team coordinated by Julien Diana, an Inserm Research Fellow at Inserm Unit 1151 “Institut Necker-Enfant Malades” [Necker Institute for Sick Children] (Inserm/CNRS/Université Paris Descartes), is focussing on a category of antimicrobial peptides, i.e. cathelicidins. Apart from their protective function, these peptides have also exhibited immunoregulatory abilities against several autoimmune diseases. As such, scientists hypothesise that cathelicidins may be involved in the control of type 1 diabetes, an autoimmune disease where certain cells in the immune system attack beta cells in the pancreas which secrete insulin.

Firstly, they observed that beta pancreatic cells in non-diseased mice produce cathelicidins and that, interestingly, this production is impaired in diabetic mice.

To test this hypothesis, they are injecting diabetic mice with cathelicidins where production is defective.

“Injecting cathelicidins inhibits the development of pancreatic inflammation and, as such, suppresses the development of autoimmune disease in these mice” states Julien Diana.

Given that the production of cathelicidins is controlled by short-chain fatty acids produced by gut bacteria, Julien Diana’s team are studying the possibility that this may by the cause of the cathelicidin deficiency associated with diabetes. Indeed, researchers have observed that diabetic mice have a lower level of short-chain fatty acids than that found in healthy mice.

By transferring part of the gut bacteria from healthy mice to diabetic mice, they are re-establishing a normal level of cathelicidin. Meanwhile, the transfer of micro-organisms reduces the occurrence of diabetes.

For the authors, “this research is further evidence of the undeniable role microbiota plays in autoimmune diseases, particularly in controlling the development of autoimmune diabetes”.

Preliminary data, as well as scientific literature, suggest that a similar mechanism may exist in humans, paving the way for new therapies against autoimmune diabetes.

Learn More +

FDA Approves The Second Phase Of Dr. Denise Faustman’s Clinical Testing Of A Type 1 Diabetes Vaccine

Faustman-BannerPublished 2 weeks ago by Albert McKeon in Diabetes, Donor Recognition, and Medical Research. Click here to read original article.

After nearly 20 years of research, Massachusetts General Hospital researcher Denise Faustman, MD, PhD, has made a promising advance in her quest to cure type 1 diabetes.

Her team recently passed a major threshold by receiving FDA clearance to test a large group of long-term diabetics with an old tuberculosis vaccine that could also combat type 1 diabetes. The phase 2 trial of the bacillus Calmette-Guérin (BCG) vaccine was announced last month at an American Diabetes Association conference in Boston, an exciting next step in Dr. Faustman’s pursuit of a therapy to reverse the disease.

While thrilled about receiving the FDA’s blessing, Dr. Faustman and her staff didn’t celebrate for long. They’re already accepting applications for patients who want to participate in the five-year trial that starts this summer.

We’re in full action mode. The phones are ringing off the hook,” Dr. Faustman says. As many as 100,000 diabetics are expected to volunteer for the clinical trial, but the MGH Immunobiology Laboratory will winnow the number of participants to 150 adults, with some receiving BCG and others taking a placebo.

Old Vaccine, New Promise

The FDA approved the phase 2 trial essentially by certifying MGH’s use of BCG that will be produced by the Japanese government. Academics usually don’t have to look around the world to find a drug supply chain, Dr. Faustman says, but her lab – in collaboration with the Bill & Melinda Gates Foundation and the World Health Organization – searched as far as Japan because it couldn’t land enough BCG from a U.S. drug manufacturer.

BCG was first used as a vaccine against tuberculosis, and it more recently targeted bladder cancer. Dr. Faustman started experimenting with the vaccine in the early 1990s. She was interested in how BCG triggers the immune system to make a protein that kills the abnormal T-cells which hinder the pancreas’ ability to produce insulin.

Her recent advance might not have happened without the insistence and generosity of former Chrysler CEO Lee Iacocca. After losing his wife, Mary, to complications from diabetes, Iacocca’s charitable foundation began supporting Dr. Faustman’s research, and in 1999 he urged her to expand her testing to mice, with the promise of continued funding.

Deserving Diabetes Patients

“We cured a late-stage diabetic mouse and saw pancreatic regeneration. No one had seen that before,” Dr. Faustman recalls. That led to a small phase 1 study in people to see if BCG could destroy the bad T-cells and prompt the good ones to produce a small amount of insulin. That phase succeeded, leading to this next stage: a longer trial on a larger number of people who have had type 1 diabetes for years.

“All type 1 diabetes intervention trials have been only in new onset cases, people only a year out from diagnosis,” Faustman says. Her team’s phase 2 trial will be “remarkable because we’re picking people who are the most deserving to rece