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Autonomic and Hemodynamic Responses to Insulin in Lean and Obese Humans¹

Metabolism Unit (M.E., L.P., C.C., E.F.) and Coronary Division (E.M., A.N., S.C., A.G., S.B., E.F.), CNR Institute of Clinical Physiology, and the Department of Internal Medicine (E.F.), University of Pisa, Pisa, Italy

Address all correspondence and requests for reprints to: E. Ferrannini, CNR Institute of Clinical Physiology, Via Savi, 8, 56126 Pisa, Italy. E-mail: PISAMET{at}PO.IFC.PI.CNR.IT

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 hyperinsulinemia (1 mU·min^-1·kg^-1 insulin clamp). In the lean group, insulin promptly (within 20 min) and consistently depressed spectral powers, both in the low-frequency and high-frequency range. These changes were 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, stroke 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 vascular 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 autonomic balance. In the obese group, all basal spectral powers were significantly lower (by 40% on average) than in the lean group, and were further reduced by insulin administration. The low-to-high frequency ratio 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). Furthermore, 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 vs. 4.45 ± 0.21 l·min^-1, P = 0.001) but lower peripheral vascular resistance (15.1 ± 0.8 vs. 19.2 ± 1.1 mmHg·min·L^-1, P = 0.002), whereas mean arterial blood pressure was similar to control (90 ± 2 vs. 86 ± 2 mmHg, P = not significant).

We conclude that physiological hyperinsulinemia causes acute desensitization of sinus node activity to both sympathetic and parasympathetic stimuli, sympathetic shift of autonomic balance, and a high-output, low-resistance hemodynamic state. In the obese, these changes are already present in the basal state, and may therefore be linked with chronic hyperinsulinemia.

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