Insulin resistance and loss of glucose-stimulated acute insulin response (AIR) are the two major and earliest defects in the course of type 2 diabetes. We investigated whether weight loss after bariatric surgery in patients with morbid obesity and type 2 diabetes could restore euglycemia and normal AIR to an intravenous glucose tolerance test (IVGTT). We studied 25 morbidly obese patients-12 with type 2 diabetes, 5 with impaired glucose tolerance, and 8 with normal glucose tolerance (NGT)-before and after a biliopancreatic diversion (BPD) with Roux-en-Y gastric bypass (RYGBP). Twelve individuals with normal BMI served as control subjects. Twelve months after surgery, in the diabetes group, BMI decreased from 53. 2 +/- 2. 0 to 29. 2 +/- 1. 7 kg/m(2), fasting glucose decreased from 9. 5 +/- 0. 83 to 4. 5 +/- 0. 13 mmol/l, and fasting insulin decreased from 168. 4 +/- 25. 9 to 37. 7 +/- 4. 4 pmol/l (mean +/- SE; P < 0. 001). AIR, the mean of insulin concentration at 2, 3, and 5 min over basal in the IVGTT, increased by 770 and 935% at 3 and 12 months after surgery, respectively (from 24. 0 +/- 22. 7 to 209 +/- 43. 4 and 248 +/- 33 VSports手机版. 1 pmol/l, respectively; P < 0,001). Conversely, in the NGT group, the AIR decreased by 40. 5% (from 660 +/- 60 to 393 +/- 93 pmol/l; P = 0. 027) 12 months after surgery. BPD with RYGBP performed in morbidly obese patients with type 2 diabetes leads to significant weight loss, euglycemia, and normal insulin sensitivity; but most importantly, it restores a normal beta-cell AIR to glucose and a normal relationship of AIR to insulin sensitivity. This is the first study to demonstrate that the lost glucose-induced AIR in patients with type 2 diabetes of mild or moderate severity is a reversible abnormality. .