GLP-1 and the Long-Term Outcome of Type 2 Diabetes Mellitus After Roux-en-Y Gastric Bypass Surgery in Morbidly Obese Subjects

Objective: To evaluate the association between glucagon-like peptide 1 (GLP-1) secretion and the long-term (>2 years) outcome of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass (RYGBP). Methods: Cross-sectional study in 18 T2DM morbidly obese subjects who underwent RYGBP but differed in the long-term outcome of T2DM (remission: G1, n = 6; relapse: G2, n = 6; lack of remission: G3: n = 6). Groups were matched for their sex, age, and body mass index. The GLP-1, glucose, C-peptide, and glucagon responses to a standardized test meal (STM) were evaluated. Insulin secretion and insulin sensitivity were estimated from the STM and by frequently sampling intravenous glucose tolerance test (FSIVGTT). Dual-energy X-ray absorptiometry was used to assess body composition. Results: Patients in G1 presented a lower area under the curve (AUC(0-120)) of glucose in response to the STM as compared with G2, and G3 (P < 0.01). In contrast, the AUC(0-120) of GLP-1 (P = 0.884) and glucagon (P = 0.630) did not differ significantly among the 3 groups. Indices of insulin secretion adjusted by the prevailing insulin sensitivity derived from STM and FSIVGTT, demonstrated larger beta-cell function in subjects in G1 as compared with G2 or G3 (Disposition Index-STM, P = 0.005; DI-FSIVGTT, P = 0.006). Body composition and inflammatory markers did not differ significantly among the 3 study groups. Conclusions: Our data show that in subjects with T2DM an enhanced GLP-1 response to meal intake is not sufficient to maintain normal glucose tolerance in the long term after RYGBP. Our data suggest that beta-cell function is a key determinant of the long-term remission of T2DM after this bariatric surgery technique.