Effects of Gastric Bypass Surgery on Insulin Resistance and Insulin Secretion in Nondiabetic Obese Patients

Roux-en-Y-Gastric-Bypass (RYGB) reduces overall and diabetes-specific mortality by 40% and over 90%. This study aims to gain insight into the underlying mechanisms of this effect. We evaluated time-courses of glucose, insulin, C-peptide, and the incretin glucagon like peptide-1 (GLP-1) following an oral glucose load. Insulin-sensitivity was measured by a hyperinsulinemic-isoglycemic-clamp-test; glucose-turnover was determined using D-[6,6-(2)H(2)] glucose. Examinations were performed in six nondiabetic patients with excess weight before (PRE: BMI: 49.3 +/- 3.2 kg/m(2)) and 7 months after RYGB (POST: BMI: 36.7 +/- 2.9 kg/m(2)), in a lean (CON: BMI: 22.6 +/- 0.6 kg/m(2)) and an obese control group (CONob) without history of gastrointestinal surgery (BMI: 34.7 +/- 1.2 kg/m(2)). RYGB reduced fasting plasma concentrations of insulin and C-peptide (P < 0.01, respectively) whereas fasting glucose concentrations remained unchanged. After RYGB increase of C-peptide concentration following glucose ingestion was significantly higher compared to all other groups (dynamic-area under the curve (Dyn-AUC): 0-90 min: POST: 984 +/- 115 ng.min/ml, PRE: 590 +/- 67 ng.min/ml, CONob: 440 +/- 44 ng.min/ml, CON: 279 +/- 22 ng.min/ml, P < 0.01 respectively). Early postprandial increase of glucose concentration was however not affected. GLP-1 concentrations following glucose ingestion were sixfold higher after RYBG than before (P = 0.01). Insulin-stimulated glucose uptake tended to increase postoperatively (M-value: PRE: 1.8 +/- 0.5, POST: 3.0 +/- 0.3, not significant (n.s.)). Endogenous glucose production (EGP) was unaffected by RYGB. Hepatic insulin resistance index improved after RYGB and was then comparable to both control groups (PRE: 29.2 +/- 4.3, POST: 12.6 +/- 1.1, P < 0.01). RYGB results in hyper-secretion of insulin and C-peptide, whereas improvements of insulin resistance are minor and seem to occur rather in the liver and the adipose tissue than in the skeletal muscle.