Changes in plasma glucose,free fatty acids (FFA), cortisol,immunoreactive human growth hormone (IRHGH) and immunoreactive insulin (IRI) after tolbutamide-induced hypoglycemia in obese subjects

Summary The investigation was carried out on 30 subjects: 21 obese subjects and 9 normal weight controls. Twelve of the obese subjects and the 9 controls received 1 g tolbutamide i.v.; the other 9 obese subjects received 1.5 g tolbutamide, all in fasting condition. Plasma glucose, FFA, cortisol, serum IRI, and IRHGH were measured before and 15, 30, 60, 90 and 120 min after tolbutamide administration. A blunted response of cortisol and IRHGH to the hypoglycemic stimulus was observed in obese subjects receiving 1 g tolbutamide. The blunted response was reversed when 1.5 g tolbutamide was injected. Glucose levels were significantly higher at 60 min in the obese who received 1 g tolbutamide as compared to the controls, and were significantly lower 30, 60 and 90 min after the tolbutamide injection in obese who received 1.5 g tolbutamide. FFA showed significantly higher values 90 and 120 min after the injection in both groups of obese subjects: dose dependency was not observed. Insulin values were significantly higher 15 min after tolbutamide injection in the obese receiving 1.5 g tolbutamide when compared to those receiving 1 g and to the controls. The blunted plasma cortisol and serum IRHGH responses were reversed when larger doses were used. Some possible explanations for the results are discussed: a hypothalamo-pituitary underresponsiveness, a lower ratio of biologically active versus biologically unactive IRI, and peripheric insulin resistance in obesity.