January 30, 2001
View Full PaperHyperinsulinemia and Autonomic Nervous System Dysfunction in Obesity
Key Result
Obesity and chronic hyperinsulinemia were associated with a 22% increase in cardiac output (P<0.03) and altered sympathovagal balance, which partially reversed with weight loss.
Study Design
Type
Observational (n=38)
Structured PICO
Is uncomplicated obesity with chronic hyperinsulinemia associated with autonomic nervous system dysfunction and altered hemodynamics compared to lean subjects?
P
Population
38 subjects (21 obese and 17 lean) evaluated for resting cardiac output, catecholamines, and heart rate variability, with a subset of 9 obese subjects re-evaluated after weight loss.
E
Exposure
Observational comparison of obesity/hyperinsulinemia; a subset of 9 obese subjects underwent 10% to 18% weight loss.
C
Comparator
Lean subjects.
O
Outcome
Resting cardiac output, plasma concentrations and timed urinary excretion of catecholamines, and 24-hour heart rate variability.surrogate
Uncomplicated obesity with chronic hyperinsulinemia is associated with a high-output hemodynamic state and sympathetic dominance, which can be partially reversed by weight loss.
Main Result
Effect estimate: 22% increase
p-value: p=<0.03
Abstract
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 lean subjects, we measured resting cardiac output (by 2-dimensional echocardiography), plasma concentrations and timed (diurnal versus nocturnal) urinary excretion of catecholamines, and 24-hour heart rate variability (by spectral analysis of ECG). In the obese versus lean subjects, cardiac output was increased by 22% ( P <0.03), and the nocturnal drop in urinary norepinephrine output was blunted ( P =0.01). Spectral power in the low-frequency range was depressed throughout 24 hours ( P <0.04). During the afternoon and early night, ie, the postprandial phase, high-frequency power was lower, heart rate was higher; and the ratio of low to high frequency, an index of sympathovagal balance, was increased in direct proportion to the degree of hyperinsulinemia 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 hyperinsulinemia is associated with a high-output, low-resistance hemodynamic state, persistent baroreflex downregulation, and episodic (postprandial) sympathetic dominance. Reversal of these changes by weight loss suggests a causal role for insulin.