IMPAIRED GROWTH-HORMONE RESPONSE TO INSULIN-INDUCED HYPOGLYCEMIA IN OBESE PATIENTS - RESTORATION BLOCKED BY RITANSERIN AFTER FENFLURAMINE ADMINISTRATION

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/1. In the controls, the expected GH increase to IIH (peak value 56±13.4 mU/1, AUC 234.4±55 mU/min/m1) 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/1, P<0.02; AUC 93.2±18.6, P<0.02). However, in comparison with the basal test, FF administration significantly (P < 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. This effect was completely antagonized by RIT administration (peak value 18±5; AUC 85.6±21). In conclusion, the reduced GH response to insulin hypoglycaemia in obese women has been confirmed in the present study. However, the restoration of the hormonal response obtained after FF administration in obese patients only, which is effectively antagonized by RIT, strongly suggests the involvement of the serotoninergic system in this impaired secretary pattern and provides indirect evidence of the failure of this system in human obesity. Copyright © 1990, Wiley Blackwell. All rights reserved