AUTONOMIC AND HEMODYNAMIC-RESPONSES TO INSULIN IN LEAN AND OBESE HUMANS

To study the acute effects of insulin on autonomic control of cardiac function, we performed spectral analysis of heart rate variability and measured cardiac dynamics (by two-dimensional echocardiography) in 18 obese (BMI = 35 +/- 1 kg m(-2)) and 14 lean (BMI = 24 +/- 1 kg m(-2)) subjects in the basal state and in response to physiological hyperins ulinemia(1 mU.min(-1).kg(-1) insulin clamp). In the lean group, insuli n promptly (within 20 min) and consistently depressed spectral powers, both in the low-frequency and high-frequency range. These changes wer e twice as large as accounted for by the concomitant changes in heart rate (68 +/- 2 to 70 +/- 2 beats/min). At the end of the 2-h clamp, st roke volume (67 +/- 4 to 76 +/- 9 ml.min(-1)) and cardiac output (4.45 +/- 0.21 to 5.06 +/- 0.55 l.min(-1)) rose, whereas peripheral vascula r resistance fell. The low-to-high frequency ratio increased from 1.7 +/- 0.2 to 2.3 +/- 0.3 (P < 0.01), indicating sympathetic shift of aut onomic balance. In the obese group, all basal spectral powers were sig nificantly lower (by 40% on average) than in the lean group, and were further reduced by insulin administration. The low-to-high frequency r atio was higher than in controls at baseline (2.4 +/- 0.4, P < 0.03), and failed to increase after insulin (2.2 +/- 0.3, P = ns). Furthermor e, obesity was associated with higher resting stroke volume (89 +/- 5 vs. 67 +/- 4 ml.min(-1), P < 0.01) and cardiac output (6.01 +/- 0.31 v s. 4.45 +/- 0.21 l.min(-1), P = 0.001) but lower peripheral vascular r esistance (15.1 +/- 0.8 vs. 19.2 +/- 1.1 mmHg.min.L-1, P = 0.002), whe reas mean arterial blood pressure was similar to control (90 +/- 2 vs. 86 +/- 2 mmHg, P = not significant). We conclude that physiological h yperinsulinemia causes acute desensitization of sinus node activity to both sympathetic and parasympathetic stimuli, sympathetic shift of au tonomic balance, and a high-output, low-resistance hemodynamic state. In the obese, these changes are already present in the basal state, an d may therefore be linked with chronic hyperinsulinemia.