Study offers clues to potential treatments for preserving, restoring insulin-producing cells

Joslin Diabetes CenterAug 12 2010

In type 1 diabetes, the body relentlessly attacks and destroys its own insulin-producing pancreatic beta cells. But a study by Joslin Diabetes Center scientists now has firmly established that some of these cells endure for many decades in a small group of people with the disease—offering clues to potential treatments for preserving and even restoring the crucial cell population.

Joslin has been awarding 50-Year Medals to people with insulin-dependent diabetes since 1972. The finding comes from the Joslin 50-Year Medalist Study, which examines this select cohort to discover protective factors for their long-term survival.

Published online by Diabetes this week, the research analyzed pancreatic function in 411 Medalists and examined nine pancreases from Medalist organ donors.

Blood samples showed that many in this group exhibit C-peptide molecules (a marker of insulin production), blood glucose levels that rise less after a meal than would be expected in the absence of insulin, and signs of autoimmune attack.

Moreover, all of the donated pancreases displayed active insulin-producing beta cells, with some of the cells scattered individually and others clumped with different kinds of hormone-producing cells in the normal pancreatic structures called islets. Most strikingly, some of the beta cells showed signs of cell proliferation, cell death and autoimmune attack.

"We've clearly demonstrated that functional beta cells are still in the pancreas," says Hillary Keenan, Ph.D., Joslin research associate and first author on the paper.

"The evidence that these insulin-producing cells are both growing and dying is very important from a treatment point of view," says George King, M.D., senior author on the paper and head of the Dianne Nunnally Hoppes Laboratory for Diabetes Complications. "If we could increase the rate of growth and decrease the rate of death, we potentially could build up more insulin-producing cells and lead to a treatment or a cure."

Another major component to the Medalist study is the pursuit of factors that protect against diabetic complications. The Medalists provide an extraordinary opportunity for this research due to the high proportion who are free from complications. This search for protective rather than risk factors is part of a paradigm shift in Joslin's diabetes complications studies, says Dr. King, who also is Joslin's chief scientific officer and a professor of medicine at Harvard Medical School.

One impetus for the study of pancreatic insulin production in the Medalist cohort came in 2004 from an insight by Medalist Elizabeth Saalfeld, a Virginia resident who then had lived with diabetes for almost 60 years. Mrs. Saalfeld noted that at times her insulin requirements were so low that she believed her body was still making the hormone. She mentioned her observation to Dr. King, and follow-up lab analyses suggested that she was right.