Insulin deficiency reduces the size of the pancreas in type 1 diabetes

People with type 1 diabetes have smaller pancreas than people without diabetes. This is surprising because insulin-producing beta cells represent only a small portion of the pancreas, so loss of beta cells in type 1 diabetes would not be expected to reduce pancreatic volume.

Now, a study of one Alabama family has led researchers at Vanderbilt University Medical Center to discover that insulin deficiency, aside from the autoimmunity associated with type 1 diabetes, is the main factor leading to significantly smaller pancreas.

Four members of this family of eight have monogenic diabetes mellitus from a rare mutation in the insulin gene, which results in insulin deficiency without autoimmunity. Magnetic resonance imaging (MRI) of the pancreas showed a smaller size and an altered shape in individuals with diabetes. This was similar to what was previously observed in individuals with type 1 diabetes. These new findings are published in Diabetes Care, a journal of the American Diabetes Association.

This is a wonderful story about one family’s ability to inform us of the process of a disease affecting millions of people. There are not many families, especially large families, that are known to have this type of diabetes, that can step forward to help us answer this question. But they answered the call, providing a really clear answer to a fundamental biological question.”

Daniel Moore, MD, PhD, Associate Professor of Pediatrics in the Ian Burr Department of Pediatrics, Endocrinology, and Diabetes

Nearly two decades ago, David Purcell and his wife, Elaine, agreed that he and three of their six children diagnosed with diabetes would take part in research in hopes of learning more about the disease. It was as simple as donating a little blood.

They were surprised years later when a researcher from the University of Chicago’s Koffler Diabetes Center called to tell them that advances in science had revealed that all four actually had monogenic diabetes due to a mutation in the insulin gene rather than type 1 diabetes.

Last year, the Pursells were contacted by VUMC researchers who were collaborating with Siri Greeley, MD, PhD, and colleagues at the Kovler Diabetes Center’s Monogenic Diabetes Registry. The Vanderbilt research team asked if the family could travel to Nashville to have accurate measurements of the pancreas at the medical center.

The VUMC research team, which includes Moore, Jordan Wright, MD, PhD, John Williams, PhD, Melissa Helms, MD, and Alvin C. Powers, MD, along with colleague Jack Verostko, PhD, at the University of Texas In Austin, it was previously found that reduced pancreatic volume was present at the time of diagnosis of type 1 diabetes. The Vanderbilt investigators also organized an international team, the Multicenter Evaluation of the Pancreas in Type 1 Diabetes (MAP-T1D), to develop a standard MRI protocol for assessing pancreatic volume and microstructure.

said Wright, an instructor in the Department of Diabetes, Endocrinology, and Metabolism and first author on a manuscript. “This is the first time we can actually demonstrate that insulin is a major factor in determining the size of the pancreas and losing it leads to a much smaller pancreas.”

David and Elaine and their now adult children, Peggy Rice, Vaughan Spanger, Chrissy Adolph, Ramsey Noss, and twin sons Parker and Martin Purcell, each had their pancreatic volume measured using the standard Vanderbilt MRI protocol. David, Chrissie, Parker, and Martin suffer from monogenic diabetes.

“When we spoke to the doctors at Kovler, they asked if we were interested in participating in some trial or research and we said, ‘Of course, anything we can do,'” David Pursell said. “When we learned that the diabetes was not caused by an immune response due to the islet cells being attacked by antibodies, we thought we might have a chance to perform an islet cell transplant.

“But also, we’re obviously all in this together. If, by virtue of our family volunteering in this research, we could help everyone else, we felt it was worth it.”