Bente Tronier

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

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.

Discrepancy Between Plasma C-Peptide and Insulin Response to Oral and Intravenous Glucose

Plasma insulin, proinsulin, and C-peptide responses to 25 g glucose orally and intravenously administered were measured in 10 healthy males. Plasma insulin response was higher during the oral load in accordance with the “incretin” concept. However, the actual amountof insulin secreted, as measured by the plasma C-peptide response, was similar during the two glucose loads. The higher plasma insulin response after oral glucose was not due to crossreactivity with proinsulin in the insulin assay. These results suggest that the higher plasma insulin response during an oral glucose load is due at least partially to a lower hepatic extraction of insulin.

Glucose counterregulation in diabetes secondary to chronic pancreatitis

Glucose counterregulation and hormonal responses after insulin-induced hypoglycemia were investigated in six patients with diabetes mellitus secondary to chronic pancreatitis, in seven with insulin-dependent (type I) diabetes mellitus, and in seven healthy subjects. Glucose counterregulation was identical in type I patients and in the patients with chronic pancreatitis, whereas both groups had impaired glucose recovery compared with the healthy subjects. The patients with chronic pancreatitis had no glucagon response to hypoglycemia, whereas epinephrine increased significantly. In an additional experiment, glucose recovery did not occur after hypoglycemia during concomitant beta-adrenoceptor blockade in these patients. In conclusion, glucose counterregulation is preserved but slightly impaired in patients with diabetes secondary to chronic pancreatitis, and the combination of total glucagon deficiency and pharmacological blockade of the metabolic actions of circulating epinephrine abolishes glucose counterregulation after hypoglycemia.