Counterregulatory hormonal responses to hypoglycaemia in Type 1 (insulin-dependent) diabetes: evidence for diminished hypothalamic-pituitary hormonal secretion

Acute insulin-induced hypoglycaemia in humans provokes autonomic neural activation and counterregulatory hormonal secretion mediated in part via hypothalamic stimulation. Many patients with Type 1 (insulin-dependent) diabetes have acquired deficiencies of counterregulatory hormonal release following hypoglycaemia. To study the integrity of the hypothalamic-pituitary and the sympatho-adrenal systems, the responses of pituitary hormones, beta-endorphin, glucagon and adrenaline to acute insulin-induced hypoglycaemia (0.2 units/kg) were examined in 16 patients with Type 1 diabetes who did not have autonomic neuropathy. To examine the effect of duration of diabetes these patients were subdivided into two groups (Group 1: 8 patients 15 years duration) and were compared with 8 normal volunteers (Group 3). The severity and time of onset of hypoglycaemia were similar in all 3 groups, but mean blood glucose recovery was slower in the diabetic groups (p<0.01). The mean responses of glucagon, adrenaline, adrenocorticotrophic hormone, prolactin and beta-endorphin were similar in all 3 groups, but the mean responses of growth hormone were lower in both diabetic groups than in the normal group (p<0.05). The mean increments of glucagon and adrenaline in the diabetic groups were lower than the normal group, but these differences did not achieve significance; glucagon secretion was preserved in several diabetic patients irrespective of duration of disease. Various hormonal responses to hypoglycaemia were absent or diminished in individual diabetic patients, and multiple hormonal deficiencies could be implicated in delaying blood glucose recovery. The demonstration of subnormal secretion of adrenaline and pituitary hormones following hypoglycaemia in individual patients supports the concept that central (hypothalamic) activation of counterregulation may be diminished in Type 1 diabetes.