Individuals with Type 1 diabetes have a smaller pancreas than people without diabetes. That is surprising because insulin-producing beta cells account for only a small fraction of the pancreas, so the lack of beta cells in Type 1 diabetes wouldn’t be expected to cut back pancreas size.

Now, a study of 1 family from Alabama has led Vanderbilt University Medical Center researchers to find that insulin deficiency, independent of the autoimmunity related to Type 1 diabetes, is the principal factor resulting in a markedly smaller pancreas.

4 members of this family of eight have monogenic diabetes from a rare mutation within the insulin gene, resulting in insulin deficiency without autoimmunity. Magnetic resonance imaging (MRI) of the pancreas showed a reduced size and altered shape within the individuals with diabetes. This was just like what had previously been observed in individuals with Type 1 diabetes. These recent findings are published in Diabetes Care, a journal of the American Diabetes Association.

This is a superb story concerning the power of a single family to tell us concerning the means of a disease that affects hundreds of thousands of individuals. There will not be many families, especially not large families, who’re known to have exactly this kind of diabetes, who could come forward to assist us answer this query. But they responded to the decision, and so they’ve provided a very clear answer to a fundamental biologic query.”

Daniel Moore, MD, PhD, Associate Professor of Pediatrics within the Ian Burr Division of Pediatric Endocrinology and Diabetes

About twenty years ago, David Pursell and his wife, Ellen, agreed that he and three of their six children who were diagnosed with diabetes would take part in research with the hope more may very well be learned concerning the disease. It was so simple as giving a bit of blood.

They were surprised years later when a researcher from the University of Chicago’s Kovler Diabetes Center called to inform them that advances in science had revealed that the 4 actually had monogenic diabetes resulting from a mutation within the insulin gene as an alternative of Type 1 diabetes.

Last 12 months, the Pursells were contacted by VUMC researchers who were collaborating with Siri Greeley, MD, PhD, and colleagues on the Kovler Diabetes Center’s Monogenic Diabetes Registry. The Vanderbilt research team asked if the family could travel to Nashville to have precise measurements of their pancreas taken on the Medical Center.

The VUMC research team, which incorporates Moore, Jordan Wright, MD, PhD, Jon Williams, PhD, Melissa Hilmes, MD, and Alvin C. Powers, MD, together with colleague Jack Virostko, PhD, at The University of Texas at Austin, had previously found the reduction in pancreas size was present on the time of Type 1 diabetes diagnosis. The Vanderbilt investigators had also organized a world team, the Multicenter Assessment of the Pancreas in Type 1 Diabetes (MAP-T1D), to develop a standardized MRI imaging protocol to evaluate pancreas volume and microarchitecture.

“We all know the pancreas is far smaller in individuals with Type 1 diabetes, but there have not been good models to grasp exactly what is going on on,” said Wright, an instructor within the Division of Diabetes, Endocrinology and Metabolism and first writer on the manuscript. “That is the primary time we are able to actually exhibit in humans that insulin is a significant component in determining pancreas size and the lack of it results in a much smaller pancreas.”

David and Ellen and their now adult children, Peggy Rice, Vaughan Spanjer, Chrissy Adolf, Ramsey Nuss, and twin sons Parker and Martin Pursell, each had their pancreas size measured using the standardized Vanderbilt MRI protocol. David, Chrissy, Parker and Martin have monogenic diabetes.

“After we talked to the doctors at Kovler, they asked if we would be taken with participating in some trials or research and we said, ‘In fact, anything we are able to do,'” said David Pursell. “After we learned our diabetes was not attributable to an immune response resulting from our islet cells being attacked by antibodies, then we thought possibly we have the prospect of getting an islet cell transplant.

“But additionally, we’re obviously all on this together. If, by virtue of our family volunteering for this research we can assist anyone else, we felt like it will be value it.”

Source:

Vanderbilt University Medical Center

Journal reference:

Wright, J.J., et al. (2023) Insulin Deficiency From Insulin Gene Mutation Results in Smaller Pancreas. Diabetes Care. doi.org/10.2337/dc22-2082.