Context: Gastric bypass surgery (GBP) results in rapid weight loss, improvement of type 2 diabetes (T2DM) and increase in incretins levels. Diet-induced weight loss also improves T2DM and may increase incretin levels.

Objective: To determine whether the magnitude of the change of the incretin levels and effect is greater after GBP compared to a low caloric diet, after equivalent weight loss.

Design and Methods: Obese women with T2DM studied before and 1 month after GBP (n=9) or after a diet-induced equivalent weight loss (n=10). Patients from both groups were matched for age, body weight, BMI, diabetes duration and control, and amount of weight loss.

Setting: Outpatient GCRC.

Main Outcome Measures: Glucose, insulin, proinsulin, glucagon, GIP and GLP-1 levels were measured after 50 gr oral glucose. The incretin effect was measured as the difference in insulin levels in response to oral and to an isoglycemic iv glucose load.

Results: At baseline, none of the outcome variables (fasting and stimulated values) were different between the GBP and the diet group. Total GLP-1 levels after oral glucose markedly increased 6 times (peak:17±6 to 112±54 pmol/L, p<0.001) and the incretin effect increased 5 times (9.4±27.5% to 44.8±12.7%, p<0.001) after GBP but not after diet. Post-prandial glucose levels (p=0.001) decreased more after GBP.

Conclusions: These data suggest that early after GBP, the greater GLP-1 and GIP release and improvement of incretin effect are related not to weight loss but rather to the surgical procedure. This could be responsible for better diabetes outcome after GBP.