Type II diabetes abrogates sex differences in endothelial function in premenopausal women

Background-Obesity is a more potent cardiovascular risk factor (CVRF) in me n than in women. Because traditional CVRFs cannot fully account for this se x difference, we tested the hypothesis that compared with men, women exhibi t more robust endothelial function independent of obesity and that this sex difference is abrogated by diabetes. Methods and Results-We studied leg blood flow (LBF) responses to graded int rafemoral artery infusions of the endothelium-dependent vasodilator methach oline chloride (Mch) and the endothelium-independent vasodilator sodium nit roprusside (SNP) in groups of lean, obese (OB), and type II diabetic (DM) p remenopausal women and age- and body mass index-matched men. LBF response t o intrafemoral administration of L-NMMA, an inhibitor of nitric oxide synth ase, was also assessed in normal men and women. Maximum LBF increments in r esponse to Mch were 347+/-57% versus 231+/-22% in lean women versus men (P< 0.05) and 203+/-25% versus 111+/-17% in OB women versus men (P<0.01), respe ctively. In DM, maximum LBF increments in response to Mch were 104+/-24% an d 138+/-33% in women and men, respectively, (P=NS). LBF decrements in respo nse to L-NMMA were 34.9+/-4.1% and 17.1+/-4.2% in women and men, respective ly (P<0.01). The response to SNP was not different between sexes and groups , Conclusions-Premenopausal nondiabetic women exhibit more robust endothelium -dependent vasodilation owing to higher rates of nitric oxide release than men. Given the protective vascular action of nitric oxide, this difference may partially explain the lower incidence of macrovascular disease in women . In premenopausal women, DM causes impairment of endothelial function beyo nd that observed with obesity alone and leads to endothelial dysfunction si milar to that observed in DM men. These findings may help explain the simil ar rates of coronary artery disease and mortality in diabetic men and women .