Growth hormone, cortisol, or both are involved in defense against, but are not critical to recovery from, hypoglycemia

We tested the hypotheses that growth hormone, cortisol, or both are involved in defense against but are not critical to recovery from prolonged hypoglycemia and that the putative roles of these hormones in defense against prolonged hypoglycemia are permissive rather than direct. To do so we studied control subjects (n = 10) and patients with growth hormone and cortisol deficiencies resulting from hypopituitarism both in the untreated state (n = 7) and with prestudy and basal intrastudy growth hormone and cortisol replacement (n = 6). Postabsorptive plasma glucose, insulin, glucagon, and epinephrine concentrations were no different in the untreated patients and controls. Twelve-hour insulin infusions, in low doses adjusted over the 1st 2 h to produce plasma glucose concentrations of 3.6 mmol/l (65 mg/dl) and then fixed at that dose, resulted in significantly (P < 0.0001) lower late plasma glucose concentrations in the patients, without and with replacement. The 12-h plasma glucose concentrations were 2.9 ± 0.1 mmol/l (53 ± 1 mg/dl) in the control subjects, 2.4 ± 0.1 mmol/l (43 ± 2 mg/dl; P < 0.001 vs. control) in the deficient patients, and 2.5 ± 0.1 mmol/l (45 ± 2 mg/dl; P < 0.01 vs. control) in the replaced patients. Rates of glucose recovery from hypoglycemia after discontinuation of insulin were identical in all three studies. Thus growth hormone, cortisol, or probably both play a demonstrable role in defense against prolonged, in contrast to short-term, hypoglycemia in humans. This does not appear to be the result of permissive actions of the hormones and is therefore best attributed to their increments during hypoglycemia. On the other hand, neither growth hormone nor cortisol is critical to the prevention of hypoglycemia after an overnight fast or to recovery from even prolonged hypoglycemia.