Impaired growth hormone response to insulin-induced hypoglycaemia in obese patients: restoration blocked by ritanserin after fenfluramine administration

Abstract

The aim of the present study was to test whether the serotoninergic system may be involved in the well known reduced growth hormone (GH) response to insulin-induced hypoglycaemia (IIH) in obese patients. Ten obese women and 10 normal-weight control women underwent three IIH tests, at 14-day intervals: the first in basal conditions, the other two after randomized administration of a serotoninergic drug, fenfluramine (FF, 120 mg/day for 7 days) and FF plus ritanserin (RIT, 30 mg/day for the first 2 days and 20 mg/day on the following days). Ritanserin is a new selective 5-HT2 blocker receptor agent. Both controls and obese patients showed similar normal basal GH levels before each test and insulin administration always effectively reduced glucose levels to values lower than 2.2 mmol/l. In the controls, the expected GH increase to IIH (peak value 56 +/- 13.4 mU/l, AUC 234.4 +/- 55 mU/min/ml) was unaffected by FF administration (peak value 43 +/- 11.4; AUC 216.8 +/- 34.8). In response to the first IIH, the obese patients showed a significantly lower GH increase than in the case of the controls (peak value 21.4 +/- 4.6 mU/l, P less than 0.02; AUC 93.2 +/- 18.6, P less than 0.02). However, in comparison with the basal test, FF administration significantly (P less than 0.001) enhanced GH response to insulin hypoglycaemia (peak value 33.4 +/- 4; AUC 150 +/- 14.6), reaching values not significantly different from those of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)