Insulin Sensitivity and Secretion Changes After Gastric Bypass in Normotolerant and Diabetic Obese Subjects

Objective: To elucidate the mechanisms of improvement/reversal of type 2 diabetes after Roux-en-Y gastric bypass (RYGB). Methods: Fourteen morbidly obese subjects, 7 with normal glucose tolerance and 7 with type 2 diabetes, were studied before and 1 month after RYGB by euglycemic hyperinsulinemic clamp (EHC), by intravenous glucose tolerance test (IVGTT) and by oral glucose tolerance test (OGTT) in 3 different sessions. Intravenous glucose tolerance test IVGTT and OGTT insulin secretion rate (ISR) and sensitivity were obtained by the minimal model. Glucose-dependent insulinotropic polypeptide (GIP) and glucagonlike peptide-1 (GLP-1) were measured. Six healthy volunteers were used as controls. Results: Total ISR largely increased in diabetic subjects only when glucose was administered orally (37.8 +/- 14.9 vs 68.3 +/- 22.8 nmol; P < 0.05, pre-operatively vs postoperatively). The first-phase insulin secretion was restored in type 2 diabetic after the IVGTT (Phi(1) x 10(-9): 104 +/- 54 vs 228 +/- 88; P < 0.05, preoperatively vs postoperatively; 242 +/- 99 in controls). Insulin sensitivity by EHC (M x 102) was slightly but significantly improved in both normotolerant and diabetic subjects (1.46 +/- 0.22 vs 1.37 +/- 0.55 mmol.min(-1.)kg(-1); P < 0.05 and 1.53 +/- 0.23 vs 1.28 +/- 0.62 mmol.min(-1).kg(-1); P < 0.05, respectively). Quantitative insulin sensitivity check index was improved in all normotolerant (0.32 +/- 0.02 vs 0.30 +/- 0.02; P < 0.05) and diabetic subjects (0.33 +/- 0.03 vs 0.31 +/- 0.02; P < 0.05). GIP and GLP-1 levels increased both at fast and after OGTT mainly in type 2 diabetic subjects. Conclusions: The large increase of ISR response to the OGTT together with the restoration of the first-phase insulin secretion in diabetic subjects might explain the reversal of type 2 diabetes after RYGB. The large incretin secretion after the oral glucose load might contribute to the increased ISR.