AIMS: The contribution of endogenous GLP-1 to β-cell function after Roux-en-Y gastric bypass surgery (RYGB) is well established in normoglycemic individuals, but not in those with post-operative hyperglycemia. We, therefore, studied the effect of GLP-1 on β-cell function in individuals with varying degrees of type 2 diabetes mellitus (T2D) control after RYGB.

MATERIALS AND METHODS: Glucose, insulin secretion rates, β-cell glucose sensitivity (BCGS), and glucagon were measured during an oral glucose tolerance test before (saline only) and at 3, 12, and 24 months (M) after RYGB with and without infusion of the GLP-1 receptor blocker exendin 9-39 (EX9). The cohort was retrospectively classified based on T2D remission status at the latest study time point: remission (REM, n=5), persistent T2D (P-T2D, n=8), or impaired glucose tolerance (IGT, n=16).

RESULTS: EX9 blunted the increase in BCGS at 3M (- 44.1%, p<0.001) and 12M (- 43.3%, p<0.001), but not at 24M (-12.4%, p=0.243). EX9 enhanced post-prandial glucagon concentrations by 62.0% at 3M (p=0.008), 46.5% at 12M (p=0.055), and 30.4% at 24M (p=0.017). EX9 counterintuitively decreased glucose concentrations at 3M in the entire cohort (p<0.001) but had no effect on glycemia at 12M and 24M in P-T2D and IGT; it minimally worsened glycemia in REM at 12M.

CONCLUSIONS: GLP-1 blockade reversed the improvement in β-cell function observed after RYGB, but this effect varied temporally and by remission status. GLP-1 blockade transiently and minimally worsened glycemia only in REM, and lowered post-prandial glucose values at 3M, regardless of remission status. This article is protected by copyright. All rights reserved.