nondiabetic patients following RYGB surgery are typically quite modest compared with the presurgery condition (3). Moreover, there appear to be 2 discrete periods of improvement. The first is immediately after surgery, at which time hepatic, but not peripheral, S I improves in response to acute energy restriction (4-6), while greater, protracted weight loss appears to be more strongly associated with improved peripheral S I (7,8). Even with significant weight loss 1 year following RYBG surgery, peripheral S I is still low compared with that of lean metabolically healthy individuals (3,5,6,9).Exercise is considered a cornerstone for obesity treatment, and while it is not generally viewed to cause substantial body weight reduction (10), it can potently improve peripheral S I and glucose control (11-13) and can reduce the risk of T2D and cardiovascular disease (14,15). There is general consensus that even a single session of moderate intensity exercise can induce an improvement in S I (16). There is also evidence that exercise can BACKGROUND. Roux-en-Y gastric bypass (RYGB) surgery causes profound weight loss and improves insulin sensitivity (S I ) in obese patients. Regular exercise can also improve S I in obese individuals; however, it is unknown whether exercise and RYGB surgery-induced weight loss would additively improve S I and other cardiometabolic factors.
METHODS.We conducted a single-blind, prospective, randomized trial with 128 men and women who recently underwent RYGB surgery (within 1-3 months). Participants were randomized to either a 6-month semi-supervised moderate exercise protocol (EX, n = 66) or a health education control (CON; n = 62) intervention. Main outcomes measured included S I and glucose effectiveness (S G ), which were determined from an intravenous glucose tolerance test and minimal modeling. Secondary outcomes measured were cardiorespiratory fitness (VO 2 peak) and body composition. Data were analyzed using an intention-to-treat (ITT) and per-protocol (PP) approach to assess the efficacy of the exercise intervention (>120 min of exercise/week).RESULTS. 119 (93%) participants completed the interventions, 95% for CON and 91% for EX. There was a significant decrease in body weight and fat mass for both groups (P < 0.001 for time effect). S I improved in both groups following the intervention (ITT: CON vs. EX; +1.64 vs. +2.24 min -1 /μU/ml, P = 0.18 for Δ, P < 0.001 for time effect). A PP analysis revealed that exercise produced an additive S I improvement (PP: CON vs. EX; +1.57 vs. +2.69 min