Science Translational Medicine: Disappearing Diabetes After Gastric Bypass Surgery

Weight loss by gastric bypass surgery alters the metabolism of individuals in ways that are different from the effects of dieting, reports a new study in the 27 April issue of Science Translational Medicine. The results are preliminary but could help researchers find new ways to treat diabetes.

“The rapid reversal of diabetes after gastric bypass surgery points to mechanisms other than weight loss involved in improved glucose levels,” said lead author Blandine Laferrère, assistant professor in medicine at Columbia University College of Physicians and Surgeons.

Already a concern in the West, diabetes is a growing public health issue worldwide. Countries like China, India, and Africa are now seeing an emergence of type 2 diabetes, particularly among children.

To figure out how to develop medications that mimic the diabetes-eliminating effects of gastric bypass surgery, scientists first need to determine why diabetes suddenly disappears after surgery. A couple of theories involve changes in hormones in the gut, as well as in certain metabolic pathways that get switched on after bypass surgery but remain inactivated after dietary weight loss.

Gastric bypass surgery lowers circulating amounts of branched chain amino acids (BCAAs) as compared to a dietary intervention. Potential mechanisms by which BCAAs may lead to glucose intolerance or insulin resistance include their effects on the liver's synthesis of glucose, pancreas function, and intracellular signaling related to metabolism. Image: C. Bickel/Science © 2011 AAAS

Gastric bypass surgery lowers circulating amounts of branched chain amino acids (BCAAs) as compared to a dietary intervention. Potential mechanisms by which BCAAs may lead to glucose intolerance or insulin resistance include their effects on the liver’s synthesis of glucose, pancreas function, and intracellular signaling related to metabolism.
Image: C. Bickel/Science © 2011 AAAS

Laferrère and colleagues looked at two small groups of severely obese, diabetic individuals who either had gastric bypass surgery or went on strict diets. Individuals in both groups lost about 20 pounds. Exercise was not a weight loss factor in the study, as the participants lead sedentary lifestyles.

By analyzing a network of biochemical compounds involved in metabolic reactions in the participants, the team found that unlike dieting, gastric bypass surgery actually changes an individual’s metabolism.

In particular, gastric bypass surgery leads to a dramatic reduction in levels of circulating amino acids in the body. By contrast, these amino acids levels stayed mostly the same in individuals who dieted.

High levels of circulating amino acids are associated with obesity, diabetes, and insulin resistance. These levels vary with the amount of protein from food and the processing of amino acids by the liver and muscle.

“Here we show greater decline of amino acids in blood levels after gastric bypass surgery than after dietary intervention,” Laferrère said. “These data suggest a role for these amino acids in the improved glycemic control after gastric bypass surgery.”

Links

Read the abstract for “Differential Metabolic Impact of Gastric Bypass Surgery Versus Dietary Intervention in Obese Diabetic Subjects Despite Identical Weight Loss.”

Visit Science Translational Medicine.