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Diabetes research challenges conventional teachings

Sara Buckallew • 12/10/18

Diabetes research challenges conventional teachings

People with Type 1 diabetes depend on daily injections of insulin to manage their blood sugar. That’s because at some point, their immune system destroyed all of the insulin-secreting pancreatic beta cells in their bodies.

Or did it?

In a recent study published in “Diabetes Care,” Indiana University School of Medicine researchers build on existing evidence that challenges the classic understanding that Type 1 diabetes means total destruction of these precious cells.

Carmella Evans-Molina, MD, PhD

“Several lines of evidence suggest that some beta cells in people with long-duration type 1 diabetes are able to survive the immune assault. At present, our understanding of the how they do this is very limited,” said Carmella Evans-Molina, MD, PhD, a lead investigator of the study. “Our research suggests these beta cells are not dead, but they are certainly not normal. We like to think of them as potentially sleeping.”

The idea of the sleepy beta cell stems from an observation that has been shared by investigators around the world. Research has shown that as many as 80 percent of people with diabetes still have low levels of mature insulin molecules in their blood, even many years after diagnosis—suggesting that beta cells are still alive.

But for the other 20 percent who no longer produce traceable amounts of insulin, it remained unclear whether beta cells had the capacity to initiate insulin production. To answer this question, Evans-Molina and Emily Sims, MD partnered with investigators from across the country to test for insulin’s precursor, known as proinsulin, in blood samples collected from more than 300 people with long-term diabetes.

Investigators measured proinsulin and C-peptide, a molecule indicative of insulin production, in the blood of participants, who were followed in the Type 1 Diabetes Exchange Registry over the course of 4 years.

Sims and Evans-Molina said that they were surprised to find that nearly 90 percent of people without measurable insulin in the blood had plenty of proinsulin and that proinsulin levels were stable over 4 years of follow-up. For people without diabetes, very little proinsulin is measurable in the blood, but high levels of this precursor in people with diabetes indicates that the beta cell isn’t able to convert insulin to the fully functional form.

But why?

Emily Sims, MD

That’s the next question that the team hopes to answer. The investigators are already performing studies to better understand the mechanisms of abnormal insulin maturation and processing in islets from people with Type 1 diabetes. They are also studying proinsulin and insulin production in relatives of people with Type 1 diabetes to identify genetic links to this phenomenon.

“Long term, we envision that agents targeting beta cell health may work in combination with immunomodulatory therapies,” Sims said. “This could maximize therapeutic outcomes in people with, or at risk for, Type 1 diabetes.”

Both Evans-Molina and Sims said that they are hopeful their findings could help lead to clinical trials that focus on improving mature insulin secretion.

For patients with the disorder, their discovery could set the alarm that pulls beta cells from their slumber and sends them back to work.

Carmella Evans-Molina, MD, PhD, is the J.O. Ritchey Scholar in Medicine, associate director of Development and Community Engagement for Center for Diabetes and Metabolic Diseases (CDMD) and director of the Diabetes research group in the Herman B Wells Center for Pediatric Research.

Emily Sims, MD, is a pediatric endocrinologist at Riley Hospital for Children at IU Health and an assistant professor of pediatrics at the IU School of Medicine Department of Pediatrics.

Additional IU researchers who contributed to this study include Raghu Mirmira, MD, PhD; Linda DiMeglio, MD; Janice Blum, PhD; Robert Considine, PhD; Teresa Mastracci, PhD; Michele Yip-Schneider, PhD; and C. Max Schmidt.

Author

Sara Buckallew

Sara Buckallew works in the IU School of Medicine Dean's Office of Strategic Communication. As Communications Coordinator, Sara supports internal and external communication needs for the Herman B Wells Center for Pediatric Research and the Center for Diabetes and Metabolic Diseases.