Hyperinsulinemia and autonomic nervous system dysfunction in obesity - Effects of weight loss

Background-Because hyperinsulinemia acutely stimulates adrenergic activity, it has been postulated that chronic hyperinsulinemia may lead to enhanced sympathetic tone and cardiovascular risk. Methods and Results-In 21 obese (body mass index, 35+/-1 kg/m(2)) and 17 le an subjects, we measured resting cardiac output (by 3-dimensional echocardi ography), plasma concentrations and timed (diurnal versus nocturnal) urinar y excretion of catecholamines, and 24-hour heart rate variability (by spect ral analysis of ECG). In the obese versus lean subjects, cardiac output was increased by 22% (P<0.03), and the nocturnal drop in urinary norepinephrin e output was blunted (P=0.01). Spectral power in the low-frequency range wa s depressed throughout 74 hours (P<0.04). During the afternoon and early ni ght, ie, the postprandial phase, high-frequency power was lower, heart rate was higher; and the ratio of low to high frequency. an index of sympathova gal balance, was increased in direct proportion to the degree of hyperinsul inemia independent of body mass index (partial r=0.43. P=0.01). In 9 obese subjects who lost 10% to 18% of their body weight, cardiac output decreased and low-frequency power returned toward normal (P<0.05). Conclusions-in free-living subjects with uncomplicated obesity, chronic hyp erinsulinemia is associated with a high-output, low-resistance hemodynamic state, persistent baroreflex downregulation, and episodic (postprandial) sy mpathetic dominance. Reversal of these changes by weight loss suggests a ca usal role for insulin.