Preventing pancreatic cell death in type 1 diabetes

Beta cells produce the hormone insulin, which regulates glucose levels in the body. Cell death occurs silently until the loss of insulin secretion capacity overwhelms the pancreas and the patient begins to show symptoms of hyperglycemia - excessive blood glucose levels. This process can take years, but until now there has been no way to detect the rate of beta cell destruction early, before hyperglycemia sets in.

Working with mice, the Yale research team identified a way to measure epigenetic changes in the expression of insulin DNA during ongoing beta cell destruction. Lead researcher Kevan C. Herold, M.D., professor of immunobiology at Yale School of Medicine and principal investigator of the Yale Autoimmunity Center of Excellence, says, "We have known for more than 40 years that type 1 and type 2 diabetes result from loss of insulin producing cells but we have never been able to detect the loss of these cells until it is too late and blood sugar levels rise."

This method provides the first biomarker for detecting beta cell loss in prediabetic mice, and, Herold says, may do the same for human patients with new-onset type 1 diabetes. "We are very eager to extend our studies to see if we can detect increased rates of beta cell death before the onset of disease as well as the effects of immune therapies on this process," Herold said. "Early detection of cell death may allow for better monitoring and earlier interventions in people at risk for developing type 1 diabetes."

There are implications for type 2 diabetes, as well. Studies in the 1980s showed that there also was loss of insulin production in this more common form of the disease. However, it has not been possible to detect the loss of the insulin-producing cells. If studies in patients prove successful, this approach may help physicians decide on which therapies are optimal for treatment and how they work.

Other authors are Eitan M. Akirav, Jasmin Lebastchi, Eva M. Galvan, Octavian Henegariu, Vitaly Ablamunits and Paul M. Lizardi of Yale, and Michael Akirav of Bar-Ilan University in Israel.

The research was supported by grants from the Juvenile Diabetes Research Foundation, and gifts from the Brehm Foundation and the Howalt family.