MECHANISMS OF ALTERED HEMODYNAMIC AND METABOLIC RESPONSES TO INSULIN IN PATIENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS AND AUTONOMIC DYSFUNCTION

Patients with autonomic neuropathy are more susceptible to insulin-ind uced hypotension than normal subjects, but the mechanisms are unclear. We quantitated the hemodynamic and metabolic effects of two doses of iv insulin (1 and 5 mU/kg.min, 120 min each) and several aspects of au tonomic function in 28 patients with insulin-dependent diabetes mellit us (IDDM) and in 7 matched normal subjects under standardized normogly cemic conditions. The autonomic function tests included those predomin antly assessing the integrity of vagal heart rate control (the expirat ion inspiration ratio during deep breathing and high frequency power o f heart rate variability) and tests measuring sympathetic nervous func tion (reflex vasoconstriction to cold and blood pressure responses to standing and handgrip). During hyperinsulinemia, heart rate increased less (2 +/- 1 vs. 6 +/- 2 beats/min; P < 0.04) and diastolic blood pre ssure fell more (-3.1 +/- 1.2 us. 0.9 +/- 2.1; P = NS) in the patients with IDDM than in the normal subjects. Forearm vascular resistance de creased significantly in the patients with IDDM [by -7.1 +/- 1.4 mm Hg /(mL/dL.min); P < 0.001 for high vs. low dose insulin], but not in the normal subjects (-0.1 +/- 2.5 mm Hg/(mL/dL.min; P = NS). Reflex vasoc onstriction to cold was inversely correlated with the decreases in dia stolic (r = -0.51; P < 0.005) and systolic (r = -0.59; P < 0.001) bloo d pressure and forearm vascular resistance (r = -0.53; P < 0.005), but not with the change in heart rate. The expiration inspiration ratio w as, however, directly correlated with the insulin-induced change in he art rate (r = 0.63; P < 0.001), but not with diastolic or systolic blo od pressure or forearm vascular resistance. Whole body (48 +/- 2 vs. 6 7 +/- 5 mu mol/kg.min; P < 0.005) and forearm (44 +/- 4 vs. 67 +/- 8 m u mol/kg min; P < 0.05) glucose uptake were significantly lower in the IDDM patients than in the normal subjects. The latter could be attrib uted to a defect in the forearm glucose arterio-venous difference (1.5 +/- 0.1 vs. 2.2 +/- 0.2 mmol/L, respectively; P < 0.01), but not in b lood flow. We conclude that both impaired vagal heart rate control and sympathetic nervous dysfunction exaggerate the hemodynamic effects of insulin in patients with IDDM and could contribute to insulin-induced hypotension.