Uncovering the Cause of Smaller Pancreas in Diabetes

Highlights:

People with type 1 diabetes have a smaller pancreas than people without diabetes
Insulin shortage is the primary cause of a much-reduced pancreas
Researchers came to this conclusion after studying four members from a family of eight who had monogenic diabetes caused by a rare mutation in the insulin gene, which results in insulin shortage

Those with type 1 diabetes have a smaller pancreas than those who do not have diabetes. It is remarkable because insulin-producing beta cells make up only a smaller portion of the pancreas. Therefore, beta cell loss in type 1 diabetes would not be expected to diminish pancreas size.

What Causes Smaller Pancreas?

However, Vanderbilt University Medical Center researchers have shown that insulin shortage, rather than the autoimmune associated with type 1 diabetes, is the primary cause contributing to a much smaller pancreas.

Four members of this family of eight have monogenic diabetes caused by a rare mutation in the insulin gene, which results in insulin shortage but is not autoimmune. In diabetics, magnetic resonance imaging (MRI) of the pancreas revealed a smaller size and a different shape. It was comparable to what had previously been reported in type 1 diabetes patients. These new findings were published in Diabetes Care.

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‘We know that people with type 1 diabetes have a smaller pancreas, but there have not been any decent models to explain why. It is the first time researchers could demonstrate in humans that insulin is a fundamental component in determining pancreas size and that its absence results in a much smaller pancreas.’

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“This is a wonderful story about the power of a single-family to inform us about the process of a disease that affects millions of people,” said Daniel Moore, MD, PhD, associate professor of Pediatrics in the Ian Burr Division of Pediatric Endocrinology and Diabetes. “There are not many families, especially not large families, who are known to have exactly this form of diabetes, who could come forward to help us answer this question. But they responded to the call, and they’ve provided a really clear answer to a fundamental biologic question.”

Family Participates in Diabetes Research

David Pursell and his wife, Ellen, agreed around two decades ago that he and three of their six children with diabetes would participate in research in the hope that more may be learned about the disease. It was as simple as donating some blood.

Years later, they were astonished when a researcher from the University of Chicago's Kovler Diabetes Center contacted them to tell them that scientific advances had revealed that the four had monogenic diabetes caused by a mutation in the insulin gene rather than type 1 diabetes.

“We know the pancreas is much smaller in individuals with type 1 diabetes, but there haven’t been good models to understand exactly what’s going on,” said Wright, an instructor in the Division of Diabetes, Endocrinology and Metabolism and first author on the manuscript. “This is the first time we can demonstrate in humans that insulin is a major factor in determining pancreas size and the loss of it leads to a much smaller pancreas.”

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VUMC researchers contacted the Pursells last year while working with Siri Greeley, M.D., Ph.D., and colleagues at the Kovler Diabetes Center's Monogenic Diabetes Registry. The Vanderbilt study team asked if the family might come to Nashville to have their pancreas precisely measured at the Medical Center.

The VUMC study team previously discovered that the reduction in pancreas size existed at the time of Type 1 diabetes diagnosis. The Vanderbilt researchers also convened an international team, the Multicenter Assessment of the Pancreas in type 1 Diabetes (MAP-T1D), to create a standardized MRI imaging methodology for assessing pancreatic volume and microarchitecture.

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David and Ellen, as well as their now-adult children Peggy Rice, Vaughan Spanjer, Chrissy Adolf, Ramsey Nuss, and twin sons Parker and Martin Pursell, had their pancreatic sizes assessed using the Vanderbilt MRI procedure. Monogenic diabetes affects David, Chrissy, Parker, and Martin.

“When we talked to the doctors at Kovler, they asked if we’d be interested in participating in some trials or research and we said, ‘Of course, anything we can do,’” said David Pursell. “When we learned our diabetes was not caused by an immune response due to our islet cells being attacked by antibodies, then we thought maybe we’ve got the chance of getting an islet cell transplant.

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“But also, we’re all in this together. If by our family volunteering for this research we can help anyone else, we felt like it would be worth it.”

Source-Medindia