The evidence is clear: Being overweight increases the risk of diabetes – or at least type 2 diabetes. Now, new research has given an odd and unexpected twist to the link between weight and diabetes risk – this time for the juvenile-onset version of the disease, known as type 1.

John Kaddis (Photo by Jann Ingmire/JAMA)

In a report published today by the Journal of the American Medical Association, researchers from City of Hope and the University of Florida, Gainesville, found that people with type 1 diabetes and those at higher risk of the disease appear to have lighter-than-normal pancreases.

Unlike type 2 diabetes, which is strongly linked to obesity, type 1 diabetes is an autoimmune disease. The immune system attacks and destroys the cells that produce the hormone insulin, which the body needs to process the sugar glucose.

Diabetes can lead to life-threatening damage to the kidneys, heart, nerves and other organs.

Looking for clues to how type 1 diabetes arises, the researchers weighed 193 pancreases taken from three types of deceased organ donors:

• Those who had type 1 diabetes
• Those who had slightly increased, but still low, risk of type 1 diabetes
• Those who had no signs of diabetes

“This is the first time anyone has looked at pancreases in this way from at-risk donors,” said John Kaddis, Ph.D., staff scientist in the Department of Research Information Sciences at City of Hope and the study’s senior author.

The researchers found that the diabetic and at-risk pancreases were significantly lighter than the normal organs. Pancreases from donors who had type 1 diabetes came in at half the weight of normal organs, while at-risk donors’ pancreases weighed only 25 percent of normal.

The researchers say the findings hint that previously unsuspected parts of the pancreas might be involved in type 1 diabetes.

“The at-risk donors could still produce insulin, so their beta cells were functional,” said Martha Campbell-Thompson, Ph.D., D.V.M., of the University of Florida, Gainesville, and first author on the report. “Yet their pancreases were smaller than normal, so something else in the organ is going awry.”

The human pancreas has two major parts: the endocrine compartment and the exocrine compartment. The endocrine compartment includes special cells that produce insulin. This part is known to be damaged in people with type 1 diabetes. The exocrine compartment produces enzymes that help the body digest foods and absorb nutrients.

“Our findings suggest a potentially unnoticed role for the exocrine portion of the pancreas in the development of type 1 diabetes,” said Kaddis. A lot of research has focused on the cells that produce insulin, but “there may be important factors in the exocrine gland that also contribute to the disease.”

The researchers hope the findings might one day lead to ways of predicting and even preventing type 1 diabetes.

“At City of Hope, the Department of Information Sciences has been involved in supporting human islet research for over a decade,” said Joyce Niland, Edward and Estelle Alexander Chair in Information Sciences. “This paper highlights a critical finding that Dr. Kaddis has helped to surface, one that could have critical implications in the treatment of type 1 diabetes.”

The scientists note that, before any preventive measures can be undertaken, more work is needed to understand exactly what causes the weight differences in pancreases of those at risk of developing type 1 diabetes.

The research team also included Clive Wasserfall, M.S., Emily Montgomery and Mark Atkinson, Ph.D., from the University of Florida, Gainesville.

The Network for Pancreatic Organ Donors with Diabetes program, funded by the Juvenile Diabetes Research Foundation International, supported the study.