Context:Patients with polycystic ovary syndrome (PCOS) have an increased prevalence of insulin resistance and display subclinical evidence of early cardiovascular disease. Metformin improves insulin sensitivity and circulating markers of cardiovascular risk in patients with PCOS, but it is unclear whether this translates into improvements in vascular function.Objective: Our objective was to evaluate the effects of metformin on arterial stiffness and endothelial function in women with PCOS. Design and Intervention:Thirty women with PCOS were assigned to consecutive 12-wk treatment periods of metformin or placebo in a randomized, double-blind, crossover design separated by an 8-wk washout. Main Outcome Measures:The primary outcome measures were assessments of arterial stiffness [augmentation index (AIx), central blood pressure, and brachial and aortic pulse wave velocity (PWV)] and endothelial function. Anthropometry, testosterone, and metabolic biochemistry (lipids, homeostasis model of assessment for insulin resistance, high-sensitivity C-reactive protein, adiponectin, and plasminogen activator inhibitor-1) were also assessed.Results: Metformin improved AIx [Ϫ6.1%; 95% confidence interval (CI) for the difference Ϫ8.5 to Ϫ3.5%; P Ͻ 0.001], aortic PWV (Ϫ0.76 m/sec; 95% CI for the difference Ϫ1.12 to Ϫ0.4 m/sec; P Ͻ 0.001), brachial PWV (Ϫ0.73 m/sec; 95% CI for the difference Ϫ1.09 to Ϫ0.38; P Ͻ 0.001), central blood pressure (P Ͻ 0.001), and endothelium-dependent (AIx after albuterol; P ϭ 0.003) and endothelium-independent (AIx after nitroglycerin; P Ͻ 0.001) vascular responses. Metformin also reduced weight (P Ͻ 0.001), waist circumference (P Ͻ 0.001), and triglycerides (P ϭ 0.004) and increased adiponectin (P ϭ 0.001) but did not affect testosterone or other metabolic measures.Conclusions: Short-term metformin therapy improves arterial stiffness and endothelial function in young women with PCOS. (J Clin Endocrinol Metab 95: 722-730, 2010) P olycystic ovary syndrome (PCOS) is the commonest endocrinopathy in women of reproductive age, affecting approximately 7% of the premenopausal population (1). In addition to its effects on reproductive health, it is now well recognized that PCOS is a metabolic disorder, characterized by increased insulin resistance (2), which leads to an excess lifetime risk of type 2 diabetes (3, 4). Patients with this condition display a cluster of metabolic disturbances, including obesity (5), dyslipidemia (6), impaired fibrinolysis (7), and hypertension (8) Abbreviations: AIx, Augmentation index; AMPK, AMP kinase; aPWV, aortic PWV; BMI, body mass index; bPWV, brachial PWV; FAI, free androgen index; HDL, high-density lipoprotein cholesterol; hsCRP, high-sensitivity C-reactive protein; HOMA-IR, homeostasis model assessment method for insulin resistance; LDL, low-density lipoprotein cholesterol; NTG, nitroglycerin; PAI-1, plasminogen activator inhibitor-1; PCOS, polycystic ovary syndrome; PWV, pulse wave velocity; TC, total cholesterol; T R , estimated aortic pulse wave velocity.

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OBJECTIVE -Our objectives were to determine the prevalence of previously undiagnosed abnormal glucose tolerance, i.e., diabetes and impaired glucose tolerance (IGT) in patients with acute coronary syndrome and to assess the utility of admission and fasting glucose in identifying diabetes in these patients.RESEARCH DESIGN AND METHODS -Glycemic status was characterized on the basis of admission plasma glucose (APG), fasting plasma glucose (FPG), and an oral glucose tolerance test (OGTT) in 140 patients admitted to the hospital with acute coronary syndrome, who were not known to have diabetes (mean Ϯ SD age 67.3 Ϯ 13.4 years; 79% men). OGTTs were performed on days 5-7 after admission.RESULTS -The prevalences of diabetes and IGT were 27 and 39%, respectively, according to OGTT criteria. Receiver operating characteristic curves showed that the area under the curve for diagnosing diabetes was 0.83 (P Ͻ 0.001) for FPG, 0.79 (P Ͻ 0.001) for APG, and 0.84 (P Ͻ 0.001) for FPG and APG applied in combination. A FPG cutoff Ն5.6 mmol/l (100 mg/dl) and/or APG Ն7.8 mmol/l (140 mg/dl) yielded a sensitivity of 89.5% and a positive predictive value of 43.6% for detecting diabetes.CONCLUSIONS -A high prevalence of abnormal glucose tolerance was seen in patients with acute coronary syndrome. The combination of FPG Ն5.6 mmol/l (100 mg/dl) and/or APG Ն7.8 mmol/l (140 mg/dl) was highly sensitive for identifying diabetes. Although weakly specific, this simple algorithm could offer a practical initial screening tool at the acute setting in the high-risk population with acute coronary syndrome.

Short-term DHEA supplementation does not significantly affect measures of arterial stiffness or endothelial function in patients with adrenal insufficiency.

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