Arterial norepinephrine concentration is inversely and independently associated with insulin clearance in obese individuals with metabolic syndrome

Abstract

Context: Impaired insulin clearance contributes to the hyperinsulinemia of obesity, yet relatively little is known concerning the pathophysiological determinants of insulin clearance in obese populations. Objective: To examine the cross-sectional relationship between insulin clearance and resting sympathetic nervous system activity in a cohort of obese subjects with metabolic syndrome. Participants and Methods: Unmedicated, nonsmoking subjects (31 male, 27 female; aged 56 ± 1 year; body mass index 33.7 ± 0.6 kg/m2) underwent euglycemic hyperinsulinemic clamp to determineinsulin sensitivity (M)andinsulin clearance, assessment of norepinephrine kinetics, peripheral arterial tonometry, Doppler echocardiography, and oral glucose tolerance test. Results: Univariate correlation analyses showed inverse associations between insulin clearance and arterial norepinephrine concentration (r=-0.44, P =.0006), calculated norepinephrine spillover rate (r=-0.33, P =.01), augmentation index (AI, r=-0.37, P =.005), and positive associations with M (r = 0.30, P =.02), Matsuda insulin sensitivity index (r = 0.27, P =.04), and cardiac output (r = 0.27, P =.04). Insulin clearance and sensitivity did not differ between genders, however females had higher AI compared to males (35 ± 3% versus 14 ± 2%, P