Abstract 3005: Angiotensin Receptor Blockade Improves Insulin Sensitivity without Altering Vascular Function in Healthy Overweight Adults
Background: Abdominal obesity is independently associated with insulin resistance and endothelial dysfunction. The purpose of this study was to investigate renin-angiotensin system activation as an underlying cause of this association in humans.
Methods and Results: Healthy overweight adults without any cardiovascular risk factors or disease (BMI>27kg·m−2, 33±10 years,29 women and 6 men) received valsartan 160 mg po QD and matching placebo for 6 weeks each in a randomized, double-blind, cross-over fashion. Endothelial function and smooth muscle function, determined by brachial flow mediated dilatation (FMD) and nitroglycerin mediated dilatation (NMD) of the brachial artery, and arterial compliance (computerized arterial waveform analyses) were determined before and after treatments. Baseline FMD (5.6 ± 5.7%) and NMD (19.9 ± 6.4%) were not significantly altered (both p>0.05) following placebo (FMD 6.2 ± 4.9%, NMD 21.1±6.6%) or valsartan (FMD 7.4 ± 7.0%, NMD 19.8 ± 8.3%). Arterial compliance similarly remained unaltered. However, insulin and insulin/glucose ratio were significantly decreased with valsartan treatment (−4.6 ± 16.0 μU.ml−1 and −0.04 ± 0.15) compared to placebo (−0.4 ± 11.6 μU.ml−1 and −0.00 ± 0.11). All other parameters were not altered by valsartan.
Conclusion: Angiotensin receptor blockade enhances insulin sensitivity even in otherwise healthy overweight adults with normal fasting glucose. However, vascular function was not improved. These findings do not support a central role of angiotensin 2 receptor activation, or insulin resistance, in the etiology of the vascular dysfunctions related solely to obesity.