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Study Investigates Smaller Pancreases in People Living with Type 1 Diabetes

Date Posted: Thursday, May 14, 2020


Dr. David Harlan participated in this newly published research which revealed new data about exocrine tissue and pancreatic cells in people with and without T1D

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David Harlan, MD (UMass 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

Over the past few years, several studies using x-ray techniques or autopsy samples have been reporting that individuals with type 1 diabetes (T1D) generally have a smaller pancreas than those without T1D.  David Harlan, MD, co-director of the UMass Diabetes Center of Excellence, participated with fellow leading expert diabetes colleagues at Vanderbilt University. The research further characterized pancreases from adult donors with type 1 diabetes compared with similarly aged donors without diabetes.  The data was published in the May 2020 issue of the journal Diabetologia.  The study found pancreases from those 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," says 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 new 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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To explore potential mechanisms which may have altered pancreas size, their research measured pancreases in three mouse models of insulin deficiency.  Data from all three models found that insulin deficiency did not appear to alter the animals’ pancreas size compared to control mice.  The mouse data suggests that the smaller pancreas size in T1D is not directly caused by insulin deficiency, however, reasons for the structural changes are still unclear.

“This new 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.

diabetologia-pancreas-type-1-diabetes-study-david-harlan.jpgThe full publication of the study can be read by clicking on the link below.

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. doi: 10.1007/s00125-020-05155-

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