Differential effect of gastric bypass versus sleeve gastrectomy on insulinotropic action of endogenous incretins

Objective: Prandial hyperinsulinemia after Roux-en-Y gastric bypass surgery (GB), and to lesser degree after sleeve gastrectomy (SG), has been attributed to rapid glucose flux from the gut and increased insulinotropic gut hormones. However, β-cell sensitivity to exogenous incretin is reduced after GB. This study examines the effect of GB versus SG on prandial glycemia and β-cell response to increasing concentrations of endogenous incretins. Methods: Glucose kinetics, insulin secretion rate (ISR), and incretin responses to 50-g oral glucose ingestion were compared between ten nondiabetic participants with GB versus nine matched individuals with SG and seven nonoperated normal glucose tolerant control individuals (CN) with and without administration of 200 mg of sitagliptin. Results: Fasting glucose and hormonal levels were similar among three groups. Increasing plasma concentrations of endogenous incretins by two- to three-fold diminished prandial glycemia and increased β-cell secretion in all three groups (p < 0.05), but insulin secretion per insulin sensitivity (i.e., disposition index) was increased only in GB (p < 0.05 for interaction). However, plot of the slope of ISR (from premeal to peak values) versus plasma glucagon-like peptide-1 concentration was smaller after GB compared with SG and CN. Conclusions: After GB, increasing incretin activity augments prandial β-cell response whereas the β-cell sensitivity to increasing plasma concentrations of endogenous incretin is diminished. (Figure presented.).