Hypoqlycemia Increases Muscle Sympathetic Nerve Activity in IDDM and Control Subjects

Abstract

OBJECTIVE: The relationship between the increase in adrenomedullary catecholamine secretion and the sympathetic response to hypoglycemia is not well understood in humans. To explore this relationship more closely, we directly recorded muscle sympathetic nerve activity (MSNA) in control subjects and in insulin-dependent diabetes mellitus (IDDM) subjects without clinically evident diabetic complications. RESEARCH DESIGN AND METHODS: Twelve IDDM subjects (22.5 ± 3.9 years of age, diabetes duration of 9.8 ± 8.3 years) and 12 age-matched control subjects were studied. MSNA was measured during insulin infusion (720 pM·m–2 ·min–1) with 30-min periods of 1) euglycemia, 2) hypoglycemia (target plasma glucose, 2.8 mM), and 3) recovery. The effect of increased insulin dose (1,440 pM· m–2 · min–1) was studied in six subjects in each group, and the effect of prolonged hypoglycemia (1 h) was studied in five IDDM subjects and four control subjects. RESULTS: MSNA levels increased in IDDM and control subjects, 31 ± 8 and 29 ± 6%, respectively, above euglycemia during hypoglycemia and returned to euglycemic levels during recovery. MSNA levels during hypoglycemia were lower in IDDM subjects than in control subjects (26 ± 3 vs. 35 ± 2 bursts/min, P < 0.01). Importantly, no relationships were found between the MSNA and epinephrine responses to hypoglycemia in either group. Increasing the insulin infusion rate did not alter the MSNA response to hypoglycemia. During prolonged hypoglycemia, MSNA remained elevated above euglycemic levels throughout hypoglycemia. CONCLUSIONS: These results demonstrate that insulin-induced hypoglycemia increases muscle sympathetic neural outflow in IDDM and control subjects. The lack of correlation between the MSNA and epinephrine responses to hypoglycemia indicates that the adrenomedullary and peripheral sympathetic responses to hypoglycemia are independently mediated.