Long-Term Effects of Roux-en-Y Gastric Bypass Surgery on Plasma Glucagon-Like Peptide-1 and Islet Function in Morbidly Obese Subjects

Context: An enlarged incretin response after Roux-en-Y gastric bypass (RYGBP) has been proposed to promote excessive beta-cell function and mass. Objective: The objective of the study was to determine whether RYGBP is associated with a steadily increased glucagon-like peptide 1 (GLP-1) response and a disruption of the relationship between insulin sensitivity and insulin secretion required to maintain plasma glucose in the normal range. Design and Patients: This was a cross-sectional study. Twenty-four women divided into three groups according to time after RYGBP (9-15, 21-30, and more than 36 months). Eight normal-weight and eight morbidly obese women served as controls. Main Outcome Measures: GLP-1 was determined after a standardized test meal. Insulin secretion (AIRg) and insulin sensitivity (S(I)) were derived from an iv glucose tolerance test. Postprandial glucose profile was recorded with a continuous glucose monitoring system. Results: Area under the curve(0-120) of GLP-1 was larger after RYGBP compared with controls (P < 0.01) but was comparable among surgical groups (P = 0.314). Time after surgery was not associated with changes in S(I) (P = 0.657), AIRg (P = 0.329), or the disposition index (DI = AIRgS(I), P = 0.915). After surgery, the GLP-1 response and the DI were not significantly correlated (P = 0.304). Glucose less than 50 mg/dl was found in operated subjects, but the proportion did not increase with time after surgery (P = 0.459). Neither the GLP-1 response (P = 0.620) nor the DI (P = 0.457) differed significantly between those with or without hypoglycemic episodes. Conclusions: Although the GLP-1 response to meal intake is steadily elevated after RYGBP, this does not result over time in the development of an inappropriate insulin secretion relative to the prevailing insulin sensitivity or the occurrence of hypoglycemic episodes. (J Clin Endocrinol Metab 94: 884-891, 2009)