Type II Diabetes Abrogates Sex Differences in Endothelial Function in Premenopausal Women

Abstract

Background-Obesity is a more potent cardiovascular risk factor (CVRF) in men than in women. Because traditional CVRFs cannot fully account for this sex difference, we tested the hypothesis that compared with men, women exhibit 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 intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (Mch) and the endothelium-independent vasodilator sodium nitroprusside (SNP) in groups of lean, obese (OB), and type II diabetic (DM) premenopausal women and age-and body mass index-matched men. LBF response to intrafemoral administration of L-NMMA, an inhibitor of nitric oxide synthase, was also assessed in normal men and women. Maximum LBF increments in response to Mch were 347Ϯ57% versus 231Ϯ22% in lean women versus men (PϽ0.05) and 203Ϯ25% versus 111Ϯ17% in OB women versus men (PϽ0.01), respectively. In DM, maximum LBF increments in response to Mch were 104Ϯ24% and 138Ϯ33% in women and men, respectively, (PϭNS). LBF decrements in response to L-NMMA were 34.9Ϯ4.1% and 17.1Ϯ4.2% in women and men, respectively (PϽ0.01). 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 beyond that observed with obesity alone and leads to endothelial dysfunction similar to that observed in DM men. These findings may help explain the similar rates of coronary artery disease and mortality in diabetic men and women.

Vascular function, insulin resistance and fatty acids

“…Interestingly, in obese women, diabetes was associated with further deterioration of endothelial function resulting in LBF responses to MCh (Fig. 6B) comparable to those in obese and diabetic males [60]. These data indicate that premenopausal females have higher NO production in response to MCh than males and that this gender difference is cancelled by Type II diabetes.…”

“…6A). The results of these studies indicated that in males, obesity was associated with impaired response to the endothelium-dependent vasodilator MCh [60]. In contrast, the response to the endothelium-independent vasodilator SNP was not different between healthy obese and lean males.…”

“…Interestingly, we discovered differences in the response to MCh between females and males. Compared to male counterparts, lean and obese females showed greater increments in LBF in response to MCh [60]. Nevertheless, obesity in the women was also associated with impaired endothelial function.…”

Blood flow response in individuals with incomplete spinal cord injuries

“…Abnormal vascular control has not been reported previously in SCI patients. However, abnormal vascular control has been seen in a variety of conditions including: aging, 14,15 race, 16,17 hypercholesterolemia, 18,19 obesity, 20 diabetes 21 ± 24 and examples of muscle deconditioning after 14 ± 20 days of bed rest. 24 ± 27 Furthermore, untrained individuals have been shown to have poor orthostatic tolerance when compared to trained individuals.…”

Lecture 5

“…Baron feels that this is true, even with obesity, but not in women who have type 2 DM. 27 A study from the Joslin Clinic showed that menopause and type 2 DM impaired microvascular reactivity, when studied with acetylcholine and nitroprusside. 28 Hormone replacement therapy improved blood flow but much less in the diabetic women.…”