Chronic complication in diabetics explained

Most patients with longstanding Type 1 diabetes have chronic gastrointestinal symptoms that significantly reduce their quality of life. And now researchers have a better understanding of why this happens.

These complications, called diabetic enteropathy, include the delayed emptying of food, irritable bowel syndrome, abdominal distension and fecal incontinence. The cause was previously unknown.

Intestinal tissues from diabetic patients and healthy people were compared in a study co-authored by Franco Folli, M.D., Ph.D., professor of medicine in the Diabetes Division of the School of Medicine. The studies were carried out by researchers at Boston Children’s Hospital and Harvard Medical School and San Raffaele Hospital in Milan, Italy, led by Paolo Fiorina, M.D., Ph.D.

“In patients with Type 1 diabetes, the cell lining of the intestine was damaged,” Dr. Folli said. “The stem cells that maintain this lining, called colonic stem cells, were altered. The culprit is found in a protein called insulin-like growth factor binding protein 3, which is produced in the liver and in higher amounts in Type 1 diabetes. It binds to a receptor protein on colonic stem cells, causing their death and, in turn, damaging the intestinal lining.”

The team also experimented with a biopharmaceutical that blocks circulating levels of the protein. Studies in diabetic mice show that the drug can reverse the colon damage.

“This has the potential to result in a new treatment for this chronic complication of longstanding Type 1 diabetes,” Dr. Folli said.

The findings were published in Cell Stem Cell.