Oral Medications May Cause More Harm in Rare Form of Diabetes

Treating a rare genetic form of diabetes with oral medications may do more harm than good.

Maturity-onset diabetes of the young (MODY1) is a rare form of diabetes caused by a range of genetic mutations that interrupt beta cell function. Although it differs from type 2 diabetes, it is often misdiagnosed because symptoms appear similar.

A recent study conducted at Washington University School of Medicine suggests that the oral medications used to stimulate beta cells to release more insulin in type 2 diabetes may actually kill those same cells in people with MODY1 by overstressing them.

"People diagnosed with type 2 diabetes are treated with oral medications that make insulin-secreting beta cells very active," said first author Benjamin D. Moore, PhD, a former postdoctoral fellow at Washington University who is now at Massachusetts General Hospital. "But the MODY1 pathway we've uncovered shows that stimulating those cells with those drugs can lead to beta cell death. That means these patients can become dependent on insulin injections much sooner."

Moore, working under Jason C. Mills, MD, PhD, associate professor of medicine at Washington University and his team identified a pathway in which hepatocyte nuclear factor 4-alpha induces expression of a gene involved in regulating the cells that secrete insulin, and that can cause MODY1 when mutated. MODY affects around 3 to 5 percent of people.

"It's important to diagnose patients as accurately as possible and to attempt to target the correct pathway," Moore said. These patients may benefit from therapies designed to target this pathway that regulates the beta cells. Their findings are published in the March 18 issue of the Journal of Biological Chemistry.

The pathway may also affect the secretion of enzymes in the stomach, liver, kidney, and intestines, and Moore and Mills believe the pathway they have identified may also be important in other disorders involving enzyme-secreting cells.

"Nature doesn't re-invent the wheel," Mills said.

"What these different cells secrete is very different, but the machinery is very similar. As with auto plants, although a BMW is very different from a Volkswagen, the factories where those cars are built are not really that different. It appears the same thing may be true for a number of these cells that secrete key enzymes in the gastrointestinal tract."