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Insulin Stimulation Reduces Aortic Wave Reflection in Adults with Metabolic Syndrome

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Abstract

Adults with metabolic syndrome (MetS) have increased fasting arterial stiffness and altered central hemodynamics that contribute, partly, to increased cardiovascular disease (CVD) risk. Although insulin affects aortic wave reflections in healthy adults, the effects in individuals with MetS are unclear. We hypothesized that insulin stimulation would reduce measures of pressure waveforms and hemodynamics in people with MetS. Thirty-five adults with obesity (27 women; 54.2 ± 6.0 yr; 37.1 ± 4.8 kg/m) were selected for MetS (ATP III criteria) following an overnight fast. Pulse wave analysis was assessed using applanation tonometry before and after a 2-h euglycemic-hyperinsulinemic clamp (90 mg/dL, 40 mU/m/min). Deconvolution analysis was used to decompose the aortic waveform [augmentation index corrected to heart rate of 75 beats/min (AIx@75); augmentation pressure (AP)] into backward and forward pressure components. Aerobic fitness (V̇o), body composition (DXA), and blood biochemistries were also assessed. Insulin significantly reduced augmentation index (AIx@75, 28.0 ± 9.6 vs. 23.0 ± 9.9%, < 0.01), augmentation pressure (14.8 ± 6.4 vs. 12.0 ± 5.7 mmHg, < 0.01), pulse pressure amplification (1.26 ± 0.01 vs. 0.03 ± 0.01, = 0.01), and inflammation [high-sensitivity C-reactive protein (hsCRP): = 0.02; matrix metallopeptidase 7 (MMP-7): = 0.03] compared to fasting. In subgroup analyses to understand HTN influence, there were no insulin stimulation differences on any outcome. V̇o, visceral fat, and blood potassium correlated with fasting AIx@75 ( = -0.39, = 0.02;  = 0.41, = 0.03; = -0.53, = 0.002). Potassium levels were also associated with insulin-mediated reductions in AP ( = 0.52, = 0.002). Our results suggest insulin stimulation improves indices of aortic reflection in adults with MetS. This study is one of the first to investigate the effects of insulin on central and peripheral hemodynamics in adults with metabolic syndrome. We provide evidence that insulin infusion reduces aortic wave reflection, potentially through a reduction in inflammation and/or via a potassium-mediated vascular response.

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