Beta cell function after weight loss: a clinical trial comparing gastric bypass surgery and intensive lifestyle intervention

Objective: The effects of various weight loss strategies on pancreatic beta cell function remain unclear. We aimed to compare the effect of intensive lifestyle intervention (ILI) and Roux-en-Y gastric bypass surgery (RYGB) on beta cell function. Design: One year controlled clinical trial (ClinicalTrials.gov identifier NCT00273104). Methods: One hundred and nineteen morbidly obese participants without known diabetes from the MOBIL study (mean (S. D.) age 43.6 (10.8) years, body mass index (BMI) 45.5 (5.6) kg/m(2), 84 women) were allocated to RYGB (n=64) or ILI (n=55). The patients underwent repeated oral glucose tolerance tests (OGTTs) and were categorised as having either normal (NGT) or abnormal glucose tolerance (AGT). Twenty-nine normal-weight subjects with NGT (age 42.6 (8.7) years, BMI 22.6 (1.5) kg/m(2), 19 women) served as controls. OGTT-based indices of beta cell function were calculated. Results: One year weight reduction was 30 % (8) after RYGB and 9 % (10) after ILI (P<0.001). Disposition index (DI) increased in all treatment groups (all P<0.05), although more in the surgery groups (both P<0.001). Stimulated proinsulin-to-insulin (PI/I) ratio decreased in both surgery groups (both P<0.001), but to a greater extent in the surgery group with AGT at baseline (P<0.001). Post surgery, patients with NGT at baseline had higher DI and lower stimulated PI/I ratio than controls (both P<0.027). Conclusions: Gastric bypass surgery improved beta cell function to a significantly greater extent than ILI. Supra-physiological insulin secretion and proinsulin processing may indicate excessive beta cell function after gastric bypass surgery. European Journal of Endocrinology 164 231-238