Valsartan Improves Insulin Sensitivity without Altering Vascular Function in Healthy Overweight Adults without the Metabolic Syndrome

ABSTRACT Background. We investigated hyperactivity of the renin-angiotensin system (RAS) as a cause of endothelial dysfunction in obese humans. Methods. Thirty five healthy overweight (BMI ϭ 33.6 Ϯ 6.6 kg m Ϫ2 ) adults (33 Ϯ 10 years old) without cardiovascular risk factors received valsartan (160 mg) orally daily or a matching placebo for 6 weeks each. Results. Baseline flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) were not altered by placebo or valsartan. However, fasting plasma insulin was significantly decreased by valsartan compared to placebo (Ϫ4.6 Ϯ 16.0 UmL Ϫ1 versus Ϫ0.4 Ϯ 11.6 UmL Ϫ1 , P ϭ 0.032) with no changes in glucose. A secondary analysis in patients with elevated waist to hip ratios (ÿ 0.85, n ϭ 18) showed an increase in FMD with valsartan. Conclusions. Our findings suggest that angiotensin 2 receptor blockade may aid in the prevention of diabetes even at the earliest stages of risk due solely to uncomplicated obesity. The lack of an improvement in FMD does not support a central role of RAS-hyperactivity in the etiology of the vascular dysfunction due solely to obesity. However, it is possible that obese patients with central adiposity may improve FMD with RAS blockade, and future investigation is warranted in this subgroup