DRC & Research News

For years, the focus of type 1 diabetes (T1D) research has been on the endocrine pancreas, as that is where the islets of Langerhans reside that secrete insulin, glucagon, and other hormones. The exocrine pancreas is primarily responsible for producing digestive enzymes, bicarbonate, and water to support digestion. However, researchers believe that autoreactive T cells within the exocrine pancreas may contribute to the destruction of insulin-producing beta cells.

A recent study found that preproinsulin (PPI)-reactive CD8+ T cells exist not only within the endocrine pancreas but in the exocrine pancreas as well. While researchers know that these cells exist at high levels in individuals with T1D, they have found that they are also reasonably populous in healthy individuals. It may be possible that in healthy individuals without T1D and those who are not autoantibody-positive (aab+), that these PPI-reactive CD8+ T cells remain undetectable to the immune system, thereby causing no negative response.

If the body should experience an up-regulation of major histocompatibility complex (MHC) class 1, this could trigger a reaction where CD8+ T cells become visible and initiate an immune response leading to the destruction of pancreatic islet cells. In turn, this could result in the development of T1D.

Researchers studied various islet areas of the human pancreas and found that donors with T1D had a greater number of PPI-reactive CD8+ T cells than nondiabetic and aab- donors, but that the cells were present in all donors. The presence becomes more abundant as T1D develops. There were also more PPI-reactive CD8+ T cells in areas close to the islets, as well as within insulin-containing islet (ICI) areas. There were fewer cells in insulin-deficient islet (IDI) areas, which indicates that insulin plays an important role in attracting PPI-specific CD8+ T cells.

According to the researchers’ findings, defective thymic selection, and the failure of systemic peripheral tolerance mechanisms may not be the primary drivers behind the development of T1D. Instead, they note that “it is likely that events leading to islet attraction of autoreactive CD8+ T cells already within the pancreas may be a crucial mechanism in T1D development.”

More research is necessary to determine why the exocrine pancreas contains so many PPI-specific CD8+ T cells and exactly how they are triggered in the development of T1D. However, this recent study sheds more light on changes within the pancreas and responses from the immune system that are involved in this disease. Scientists can continue building on these findings moving forward.

Though not involved with this study, the Diabetes Research Connection (DRC) strives to continue advancing research around T1D by providing critical funding to early-career scientists. Contributions from individuals, corporations, and foundations make it possible for scientists to carry out novel, peer-reviewed studies focused on improving diagnosis, treatment, and management of T1D, as well as one day finding a cure. To learn more about current projects and how to support these efforts, visit https://diabetesresearchconnection.org. 

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During pregnancy, women are tested for gestational diabetes mellitus (GDM) to manage their overall health. Gestational diabetes complications can put both women and their babies at risk if not properly managed. While this type of diabetes typically resolves after childbirth, one study found that the condition may help identify women at risk for diabetes – either type 1 or type 2 – in the future.

A study involving 435 Finnish women who had GDM were compared to a control group of healthy women who were pair-matched for age, parity, delivery date, and no previous history of diabetes. The data was collected over ten years between 1984 and 1994. Researchers found that women who developed GDM were at increased risk of developing type 1 or type 2 diabetes if their GDM required insulin treatment, and they had at least one autoantibody. The more autoantibodies they had, whether islet cell autoantibodies (ICAs), GAD antibodies (GADA), insulin autoantibodies (IAAs), or the protein tyrosine phosphatase-related protein 2 molecule (IA-2As), the more at risk for diabetes.

Out of the 435 women diagnosed with GDM, 20 developed type 1 diabetes (T1D), and 23 developed type 2 diabetes (T2D), while none of the women in the control group developed either type of diabetes. In addition, the women who developed type 1 diabetes were younger than those who developed type 2 diabetes at the time of initial blood sampling and had a shorter diabetes-free period. A follow-up survey to determine whether type 1 or type 2 diabetes occurred was completed an average of about 6 years after they had GDM.

In total, 155 women with GDM required insulin therapy to treat their condition, and that included 18 of the 20 women who later developed T1D and 18 of the 23 women who developed T2D. Interestingly, almost equal percentages of women treated with insulin and those who were not, 16.7% and 16.9% respectively, had reactivity to at least one autoantibody. Overall, the positive predictive value of autoantibodies was higher in women with GDM than in the control group, with a greater number of autoantibodies occurring in those who went on to be diagnosed with T1D or T2D.

This study shows how GDM may indicate an increased risk of impaired glucose tolerance or destruction of insulin-producing beta cells, leading to T2D and T1D. According to the researchers, “The risk of developing type 1 diabetes after GDM is increased if the woman is ≤30 years of age during pregnancy, needs insulin therapy for GDM, and tests positive for ICAs and/or GADAs.” Some discrepancy in results could be due to other gestational diabetes complications that were not included in the study. In general, if a woman fits within these criteria, it may be beneficial to continue closely monitoring her health after pregnancy to detect diabetes early on.

It is these types of studies that help improve understanding of diabetes risk and early detection. The Diabetes Research Connection (DRC), though not involved in this study, supports type 1 diabetes research by providing critical funding to early-career scientists. One hundred percent of funds go directly to scientists for their projects. Learn more about current projects and how to help by visiting https://diabetesresearchconnection.org.

Please DONATE NOW so DRC can keep bringing you credible, peer-reviewed T1D news and research.

Thank you

It is safe to say that 2020 has been unlike any other year. That being said, DRC’s goal for this year has been to find new ways to connect with our community. DRC has had several virtual gatherings ranging from research updates to DRC’s 3rd Annual Dance for Diabetes. If you would like to view them, they will be posted below in order of the date that they took place.

Reducing Stress in Times of Uncertainty with Felise Levine Ph.D. 4/28/2020: View it Here.

Exciting Update on Type 1 Diabetes (T1D) Research with Vincenzo Cirulli Ph.D. 5/19/2020: View it Here. 

Ask Me Anything: Dr. Moore and the Long Road of Type 1 Diabetes (T1D) Care and Discovery with Daniel Moore Ph.D. 6/23/2020: View it Here.

Beyond Stem Cells: A New Paradigm for Regenerative Medicine with Duc Dong Ph.D. 7/14/2020: View it Here.

DRC’s 3rd Annual Dance for Diabetes Virtual Party: View it Here.

Preserving Retinal Cells Survival with Anne Hanneken M.D. and Frans Vinberg Ph.D. 11/10/2020: View it Here.

Although this has been an interesting year, we continue to find creative ways to connect with our community. We are looking forward to 2021 and having these exciting updates and events in person!