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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 https://diabetesresearchconnection.org.

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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 https://diabetesresearchconnection.org.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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