Role of gut peptide in diabetes remission after Roux-en-Y gastric bypass surgery

Abstract

Roux-en-Y gastric bypass surgery results in the resolution of type 2 diabetes in ∼60% of cases. Pre-surgery beta-cell function, with the large and sustained weight loss resulting from the surgery, are the main predictors of diabetes remission. However, enteric mechanisms, independent of weight loss, have been identified as important players. They include, among others, changes in intestinal metabolism, the gut hormones, the bile acids and the microbiome. The enhanced release of glucagon-like peptide 1 (GLP-1) contribute to the improvement of the incretin effect on insulin secretion during meals. GLP-1 and other gut peptides such as peptide YY and oxyntomodulin, may also contribute to the increased satiety and the decreased reward power of food observed after bypass, both contributing to decreased food intake and sustained weight loss. Although enteric factors are key for the full recovery of beta cell function during meals, the recovery of beta cell function in response to an IV glucose stimulus is more modest in magnitude, even in individual in diabetes remission. This may explain, in part, the long-term diabetes relapse in some patients. With the improvement of gut-mediated improved insulin secretion, RYGB results in large increase in insulin sensitivity and clearance, both contributors to improved glucose metabolism.