Diabetes May Start in the Intestines, Research Suggests

Scientists at Washington University School of Medicine in St. Louis have made a surprising discovery about the origin of diabetes. Their research suggests that problems controlling blood sugar - the hallmark of diabetes - may begin in the intestines.

The new study, in mice, may upend long-held theories about the causes of the disease. Because insulin is produced in the pancreas and sugar is stored in the liver, many scientists have looked to those organs for the underlying causes of diabetes.

The findings are reported Feb. 16 in the journal Cell Host & Microbe.

In the new research, scientists studied mice that are unable to make fatty acid synthase (FAS) in the intestine. FAS, an enzyme crucial for the production of lipids, is regulated by insulin, and people with diabetes have defects in FAS. Mice without the enzyme in the intestines develop chronic inflammation in the gut, a powerful predictor of diabetes.

"Diabetes may indeed start in your gut," says principal investigator Clay F. Semenkovich, MD. "When people become resistant to insulin, as happens when they gain weight, FAS doesn't work properly, which causes inflammation that, in turn, can lead to diabetes."

First author Xiaochao Wei, PhD, and Semenkovich, the Herbert S. Gasser Professor of Medicine, professor of cell biology and physiology and director of the Division of Endocrinology, Metabolism and Lipid Research, collaborated with specialists in gastroenterology and genome sciences to determine what happens in mice that can't make FAS in their intestines.

When it comes to managing diabetes, much of the focus is on insulin and the level of glucose circulating in the blood. Yet diabetes affects many body systems, including the digestion system. Both the disease and a certain class of diabetes drugs cause the movement of food through the digestive tract to slow down. These drugs may also trigger gastrointestinal distress, particularly when first beginning the medication.

Effect of Medications

Certain drugs prescribed for diabetes, called alpha-glucosidase inhibitors, slow down the digestive process. These medications are also known as starch blockers because they inhibit enzymes involved in breaking down carbohydrates. Carbs are a concern for diabetics because they trigger the most dramatic spikes in blood glucose levels in comparison to other macronutrients. Alpha-glucosidase inhibitors limit these drastic increases by slowing down the digestion of both sugar and starches. Blood glucose levels drop after eating and can be be tested about 90 minutes to two hours following a meal.

"The first striking thing we saw was that the mice began losing weight," says Wei, a research instructor in medicine. "They had diarrhea and other gastrointestinal symptoms, and when we looked closely at the tissue in the gut, we found a lot of inflammation."