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Smaller Pancreas Size in People with Type 1 Diabetes Suggests It's More than Just a Beta Cell Problem

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David Harlan, MD (UMass Chan Diabetes Center of Excellence) and Alvin Powers, MD (Vanderbilt Diabetes Center) co-chairing a session at the Network for Pancreatic Organ Donors with Diabetes annual meeting

Several recent studies using x-ray techniques or autopsy samples have reported that individuals with type 1 diabetes (T1D) generally have a smaller pancreas than those without T1D.  David Harlan, MD, co-director of the UMass Chan Diabetes Center of Excellence, collaborated with fellow diabetes experts from Vanderbilt University on a study published May 2020 in Diabetologia that found pancreases from people with both longstanding and recent-onset type 1 diabetes were approximately 45% smaller than pancreases from donors without diabetes.

“In science, it's dangerous and humbling to ever assume anything without data," said Dr. Harlan.  "For decades, the leading hypothesis to explain what goes wrong in individuals destined to develop T1D assumed they started with the same number of pancreatic insulin producing cells as others." 

Dr. Harlan pointed out other longstanding assumptions including how "it was thought that their [people with type 1 diabetes] pancreas was otherwise normal, in other words, that T1D was a beta cell specific disease."

Beta cells are the pancreatic cells that make and secrete insulin, but they represent only a very small portion of the pancreas - only about 1% of its volume.  A healthy adult pancreas is composed primarily of so called “exocrine tissue” (i.e. cells that make enzymes and fluids essential for digestion) and the ducts to deliver those things to the gut. 

This newly published research showed that humans with T1D have far less exocrine tissue than individuals without diabetes, that the exocrine tissue appeared be fibrotic (“scarred”), and that these changes were evident even early after T1D developed.  The actual exocrine cells were not smaller in size, there simply were not as many of them.

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“This data shows that the whole pancreas is affected in the disease process causing T1D, not just the insulin producing beta cells.  We know that the immune system attacks the beta cells in individuals destined to develop T1D, but these data raise the possibility that other pancreatic abnormalities are involved.  Further, we speculate that those abnormalities may play a role in triggering that anti-beta cell immune response,“ added Dr. Harlan.

Decreased pancreatic acinar cell number in type 1 diabetes

Wright JJ, Saunders DC, Dai C, Poffenberger G, Cairns B, Serreze DV, Harlan DM, Bottino R, Brissova M, Powers AC.

Diabetologia. 2020 May 9

March 2023 Update

Dr. Harlan has served a mentoring role to Drs. Wright & Virostko who significantly extend earlier observations in the following Endocrine Society publication.

Longitudinal MRI shows progressive decline in pancreas size and altered pancreas shape in type 1 diabetes 

The Journal of Clinical Endocrinology & Metabolism. 2023 March 20

 

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