ABNORMAL ARGININE-VASOPRESSIN RESPONSES TO METOCLOPRAMIDE AND INSULIN-INDUCED HYPOGLYCEMIA IN TYPE-I DIABETES-MELLITUS

Alterations in the control of arginine-vasopressin (AVP) secretion have been described in type I diabetes mellitus. In order to gain a better insight into this problem, we examined whether insulin-dependent diabetics in good metabolic conditions and without diabetic complications had an abnormal AVP responsiveness to metoclopramide (MCP), an AVP-stimulating agent with a central site of action. In addition, we tested the AVP response to insulin-induced hypoglycemia in the same subjects. Twenty insulin-dependent diabetic men without neuropathy or other diabetic complications were divided into two groups according to the duration of their illness (10 patients who had been diabetic for less than 10 years, group 1, and 10 patients who had been diabetic for more than 10 years, group 2). Eleven age- and weight-matched normal men participated as controls. All groups were tested with MCP (20 mg in an intravenous bolus) and. on a different occasion, with insulin-induced (0.15 IU/kg) hypoglycemia. Experiments started after optimization of the metabolic status of the diabetic men by 3 days of treatment with continuous subcutaneous insulin infusion. Basal concentrations of AVP were similar in all groups (diabetics of group 1: 2.2 ± 0.2 pmol/l, mean ± SE; group 2: 2.3 ± 0.2 pmol/l; normal controls: 2.2 ± 0.2 pmol/l). Administration of MCP induced a striking elevation of plasma AVP levels in the normal controls and in the diabetic subjects of groups 1 and 2. All subjects showed a mean peak response at 15 min. However, the AVP rise was significantly higher in the diabetic men (peak, mean ± SE: group 1 = 7.3 ± 0.6; group 2 = 6.9 ± 0.3 pmol/l) than in the control subjects (4.9 ± 0.4 pmol/l). There were no significant differences in the AVP response to MCP between groups 1 and 2. Insulin induced a similar hypoglycemic nadir in all subjects at 30 min; however, the diabetic subjects of groups 1 and 2 had a delayed recovery in blood glucose levels. The hypoglycemic pattern was similar in the diabetics of groups 1 and 2. All subjects showed mean AVP peak responses at 30 min, simultaneously with the blood glucose nadir. Hypoglycemia induced a striking AVP increase in the normal controls (peak levels: 4.3 ± 0.4 pmol/l). However, significantly higher AVP responses to hypoglycemia were observed in the diabetic men of groups 1 and 2 (peak levels: 7.1 ± 0.5 and 7.0 ± 0.4 pmol/l, respectively) than in the normal controls. The AVP response to hypoglycemia was similar in groups 1 and 2. These data indicate that a hypothalamic pituitary disorder affects the AVP response to MCP and insulin-induced hypoglycemia in well-controlled type I diabetic men without diabetic complications. Since cholinergic pathways are involved in the mechanisms of action of both MCP and insulin-induced hypoglycemia on AVP, alterations in cholinergic neurotransmission may be supposed to be involved in insulin-dependent diabetic men. © 1990 S. Karger AG, Basel.