Recent research provides a molecular basis for why 80 percent of patients with longstanding type 1 diabetes have chronic gastrointestinal symptoms including gastroparesis (delayed emptying of food), irritable bowel syndrome, abdominal distension and faecal incontinence, significantly reducing their quality of life. These symptoms are collectively called diabetic enteropathy. The cause of diabetic enteropathy was previously unknown.
Altered colonic stem cells
Franco Folli, M.D., Ph.D., professor of medicine in the Diabetes Division of the School of Medicine at The University of Texas Health Science Centre at San Antonio, is co-author on the findings presented in Cell Stem Cell. The studies were carried out by researchers at Boston Children's Hospital and Harvard Medical School in Boston and San Raffaele Hospital in Milan, Italy, led by Paolo Fiorina, M.D., Ph.D.
"Intestinal tissues from diabetic patients and healthy individuals were compared," Dr Folli said. "In patients with type 1 diabetes, the cell lining of the intestine was damaged. 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 (IGFBP3), which is produced in the liver and in higher amounts in type 1 diabetes. IGFBP3 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, also presented in Cell Stem Cell, show that the drug can reverse the colon damage.
"This is a very exciting finding, obtained by studying patients' cells, that has the potential to result in a new treatment for this chronic complication of longstanding type 1 diabetes," Dr Folli said.