The Role of β-Cell Function and Insulin Sensitivity in the Remission of Type 2 Diabetes after Gastric Bypass Surgery

Context: Bariatric surgery can induce remission in a high proportion of severely obese patients with type 2 diabetes mellitus (T2DM). Objective: Our objective was to investigate predictors and mechanisms of surgery-induced diabetes remission. Patients and Setting: Forty-three morbidly obese subjects (body mass index = 45.6 +/- 5.0 kg/m(2)), 32 with T2DM and 11 nondiabetic [normal glucose tolerance (NGT)], participated at a clinical research center. Intervention: Patients underwent Roux-en-Y gastric bypass. Main Outcome Measures: Diabetes remission and beta-cell function were evaluated. Results: Subjects were tested before and 45 d and 1 yr after surgery. Weight decreased similarly in T2DM and NGT(-39 kg at 1 yr, P < 0.0001). Insulin sensitivity improved in both groups in proportion to the changes in body mass index but remained lower in T2DM than NGT (386 +/- 91 vs. 479 +/- 89 ml/min . m(2), P < 0.01). Based on glycosylated hemoglobin and oral glucose testing, diabetes had remitted in nine patients at 45 d and in an additional 16 at 1 yr. In T2DM, beta-cell glucose sensitivity increased early after surgery but was no further improved and still abnormal at 1 yr [median, 48 (coefficient interval, 53) pmol/min . m(2) . mM vs. median, 100 (coefficient interval, 68) of NGT, P < 0.001]. Baseline beta-cell glucose sensitivity was progressively worse in early remitters, late remitters, and nonremitters (median, 54[coefficient interval, 50] vs. median, 22[coefficient interval, 26] vs. median, 4[coefficient interval, 10] pmol/min . m(2) . mM) and, by logistic regression, was the only predictor of failure [odds ratio for bottom tertile = 7.9 (95% confidence interval = 1.2-51.9); P = 0.03]. Conclusions: In morbid obesity, Roux-en-Y gastric bypass causes rapid and profound metabolic adaptations; insulin sensitivity improves in proportion to the weight loss, and beta-cell glucose sensitivity increases independently of weight loss. Over a period of 1 yr after surgery, diabetes remission depends on the starting degree of beta-cell dysfunction. (J Clin Endocrinol Metab 96: E1372-E1379, 2011)