ACUTE EFFECTS OF OCTREOTIDE, A LONG-ACTING SOMATOSTATIN ANALOG, ON THE INSULINEMIC AND GLYCEMIC RESPONSES TO A MIXED MEAL IN PATIENTS WITH ESSENTIAL OBESITY - A DOSE-RESPONSE STUDY

We investigated the effects of single different doses of the long acting somatostatin analog octreotide on the insulinemic and glycemic responses to a mixed meal in eleven patients with essential obesity (10F-1M; age 42.2+/-4.1 years; BMI 38.1+/-1.6 kg/m(2); waist/hip ratio 0.9+/-0.04). They underwent four different tests according to a randomized, single blind design: at 07.30 hr the patients received (a) normal saline (1 ml s.c.); octreotide (b) 25 mu g s.c. or (c) 50 mu g s.c. or (d) 100 mu g s.c. From 08.00 to 08.15 hr the patients were given a fluid mixed meal (375 kcal: 53.3% carbohydrate, 30% fat, 16.7% protein). Mean blood glucose peak after placebo was: 125+/-6 mg/dl, p<0.05 vs baseline (82+/-4 mg/dl). Blood glucose peaks after the meal were increased even if not significantly as compared to placebo either after octreotide 100 mu g (169+/-11 mg/dl) or 50 mu g (167+/-9 mg/dl) or 25 mu g (158+/-10 mg/dl). Mean baseline (07.00 and 07.30 hr samples) fasting insulin levels were significantly lowered with respect to placebo (23+/-4 mu U/ml). by the administration of each dose of octreotide (25 mu g: 1.2+/-0.9; 50 mu g: 1.9+/-0.9; 100 mu g: 1.7+/-0.7 mu U/ml). Following the administration of the mixed meal a highly significant increase in serum insulin levels after saline was observed (peak: 106.9+/-16 mu U/ml). After octreotide serum insulin peaks after the meal were significantly lower as compared to saline either after octreotide 100 mu g (20.3+/-4.1 mu U/ml) or 50 mu g (23+/-3.4 mu U/ml) or 25 mu g (36+/-12 mu U/ml) without significant differences between each regimen. It can be hypothesized that, at least in a part of obese patients, the administration of even low doses of octreotide may result on one side in a direct inhibitory effect on insulin secretion at the pancreatic level and on the other in a facilitatory action on the effects of insulin at the peripheral level.