Diabetes Care, Vol 17, Issue 7 673-680, Copyright © 1994 by American Diabetes Association
Hypoglycemia increases muscle sympathetic nerve activity in IDDM and control subjects
RP Hoffman, CA Sinkey and EA Anderson
Department of Pediatrics, College of Medicine, University of Iowa, Iowa City 52242.
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 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.