A person with type 1 diabetes has a smaller pancreas than a person without the disease. This is unexpected because insulin-producing beta-cells make up a very small part of the pancreas, and their loss in type 1 diabetes should not result in a reduction in pancreas size.
Researchers at Vanderbilt University Medical Center have now determined from a study of one Alabama family that the primary cause of a noticeably smaller pancreas is insulin deficiency, not the autoimmune disease associated with type 1 diabetes.
Four members of this family of eight have monogenic diabetes from a rare mutation in the insulin gene that results in insulin deficiency without autoimmunity. Magnetic resonance imaging (MRI) of the pancreas has shown reduced size and 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 an amazing story about the power of one family to inform us about a disease process 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 aren’t many families, especially not large families, that are known to have exactly this form of diabetes that could help us answer that question. But they rose to the challenge and provided a really clear answer to a fundamental biological question.”
About two decades ago, David Pursell and his wife, Ellen, agreed that he and three of their six children who had been diagnosed with diabetes would participate in research in the hope of learning more about the disease. It was as simple as giving some blood.
Years later, they were surprised when a researcher at the Kovler Diabetes Center at the University of Chicago called to tell them that advances in science had revealed that the four actually had monogenic diabetes due to a mutation in the insulin gene instead of type 1 diabetes.
Last year, the Pursells were contacted by VUMC researchers working 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 their pancreas accurately measured at the medical center.
The VUMC research team, which includes Moore, Jordan Wright, MD, PhD, Jon Williams, PhD, Melissa Hilmes, MD, and Alvin C. Powers, MD, along with colleague Jack Virostek, PhD, at the University of Texas at Austin, previously found that reduction in pancreatic size was present at the time of diagnosis of type 1 diabetes. Vanderbilt investigators also organized an international team, the Multicenter Assessment of the Pancreas in Type 1 Diabetes (MAP-T1D), to develop a standardized MRI imaging protocol to assess pancreatic volume and microarchitecture.
“We know that the pancreas is much smaller in individuals with type 1 diabetes, but there aren’t good models to understand exactly what’s going on,” said Wright, an instructor in the Department of Diabetes, Endocrinology and Metabolism and first author of the study. manuscript. “This is the first time we can actually show in humans that insulin is a major factor in determining the size of the pancreas, and that its loss leads to 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 a standardized Vanderbilt MRI protocol. David, Chrissy, Parker and Martin have monogenic diabetes.
“When we talked to the doctors at Kovler, they asked us if we would be interested in participating in any trials or research, and we said, ‘Sure, we can do anything,'” David Pursell said. “When we learned that our diabetes was not caused by an immune response caused by antibodies attacking our islet cells, we thought we might have a chance for an islet cell transplant.
“But we’re also obviously all in this together. If we can help someone else through our family’s voluntary participation in this research, we felt it would be worth it.”
