Hormonal, Metabolic, and Cardiovascular Responses to Hypoglycemia in Diabetic Autonomic Neuropathy

Abstract

Hormonal, metabolic, and cardiovascular responses to insulin-induced hypoglycemia were investigated in 10 juvenile-onset diabetics who showed signs of autonomic neuropathy, in 8 control patients of similar age and duration of diabetes without neuropathy, and in 6 healthy subjects. In an attempt to normalize intermediary metabolism, the diabetics were treated with soluble insulin only (given subcutaneously and intravenously) for 48 h preceding the study.

Plasma epinephrine concentrations were significantly lower in patients with autonomic neuropathy before the experiment as well as 15 min after serum glucose nadir compared with diabetics without neuropathy (P < 0.05), indicating impaired sympathoadrenal activity. Plasma norepinephrine responses did not differ significantly. No significant increase was found in glucagon concentrations in patients with autonomic neuropathy, whereas a small increment was found in diabetics without neuropathy. Growth hormone and cortisol responses were similar in the two patient groups, and serum free insulin concentrations were also similar. In spite of blunted responses of glucagon and of epinephrine in the patients with autonomic neuropathy, serum glucose responses were similar to those of the diabetics without autonomic neuropathy. Furthermore, rate of lipolysis, as judged from FFA and glycerol concentrations, as well as systolic blood pressure increments were significantly greater (P < 0.05) in patients with autonomic neuropathy than in diabetics without neuropathy.

In conclusion, during insulin-induced hypoglycemia, patients with autonomic neuropathy had impaired activation of the adrenal medulla, probably due to sympathetic neuropathy. Furthermore, they had no increase in glucagon concentrations. Compared with noneuro-pathic diabetics, serum glucose recovery was unaffected and lipolytic responses and blood pressure increments were exaggerated, suggesting increased sensitivity of hepatic glycogenolysis, adipose tissue lipolysis, and the cardiovascular system toward the action of catecholamines in diabetics with autonomic neuropathy.