Generalized impairment of vasodilator reactivity during hyperinsulinemia in patients with obesity-related metabolic syndrome.

Defective insulin-dependent vasodilation might contribute importantly to metabolic and vascular abnormalities of the metabolic syndrome (MetS). However, despite extensive investigation, the precise mechanisms involved in insulin's vasoactive effects have not been fully elucidated. Therefore, this study sought to better characterize insulin's physiological actions on vascular reactivity and their potential derangement in the MetS. Forearm blood flow responses to graded doses of acetylcholine, sodium nitroprusside, and verapamil were assessed by strain-gauge plethysmography in patients with obesity-related MetS (n = 20) and in matched controls (n = 18) before and after intra-arterial infusion of insulin (0.2 mU·kg(-1)·min(-1)). Possible involvement of increased oxidative stress in the impaired insulin-stimulated vasodilator responsiveness of patients with MetS (n = 12) was also investigated using vitamin C (25 mg/min). In control subjects, significant potentiation of the vasodilator responses to acetylcholine, nitroprusside, and verapamil was observed after insulin infusion (all P < 0.05). However, no significant change in vasodilator reactivity to either of these drugs was observed following hyperinsulinemia in patients with MetS (all P > 0.05). Interestingly, administration of vitamin C to patients with MetS during hyperinsulinemia significantly enhanced the vasodilator responsiveness to acetylcholine, nitroprusside, and verapamil (all P < 0.05 vs. hyperinsulinemia alone). In conclusion, insulin exerts a generalized facilitatory action on vasodilator reactivity, and this effect is impaired in patients with MetS likely because of increased oxidative stress. Given the importance of vasodilator reactivity in affecting glucose disposal and vascular homeostasis, this defect may then contribute to the development of metabolic and vascular complications in insulin-resistant states.

Early vascular and metabolic effects of rosuvastatin compared with simvastatin in patients with type 2 diabetes.

OBJECTIVE: To compare the short-term effects of rosuvastatin and simvastatin on insulin-resistance and endothelial dysfunction in middle-aged patients with type 2 diabetes and mild untreated dyslipidemia. METHODS AND DESIGN: 29 Subjects randomly assigned to rosuvastatin 20mg/daily or simvastatin 20mg/daily for 4 weeks. Following data collected both pre- and post-treatment: fasting glucose, lipids, hs CRP, TNF-alpha, insulin sensitivity measured with euglycemic-hyperinsulinemic clamp and flow-mediated dilation with brachial artery reactivity technique. RESULTS: Both treatments markedly reduced LDL cholesterol (p<0.001 for both). Insulin sensitivity did not change from relative baseline values in both groups, as well as fasting glucose and adiponectin. Simvastatin significantly improved flow-mediated dilation (p<0.01), to a greater extent than in patients taking rosuvastatin (p=0.09). We found no association between flow-mediated dilation improvement, LDL reduction and changes in hs CRP levels. CONCLUSION: In type 2 diabetic individuals rosuvastatin was less effective than simvastatin at improving endothelium-dependent vasodilation within one month, without affecting insulin-resistance, adiponectin levels and inflammation.

Fish oil supplementation improves endothelial function in normoglycemic offspring of patients with type 2 diabetes.

OBJECTIVE: Offspring of patients with type 2 diabetes (OPDs) exhibits endothelial dysfunction (ED) associated with a chronic inflammatory state. N-3 polyunsaturated fatty acids (n-3 PUFA) may have antioxidant and anti-inflammatory properties that are beneficial for cardiovascular and metabolic health. Therefore, in the present study, we tested the hypothesis that dietary supplementation with fish oil rich in n-3 PUFA may improve ED in otherwise healthy OPDs. METHODS AND DESIGN: A double-blind, placebo-controlled trial was conducted with 50 OPDs. Participants were randomized to treatment with either placebo or n-3 PUFA (2g/day) for 12 weeks. Before and after treatment we evaluated endothelial function (using flow-mediated dilation (FMD) of the brachial artery), circulating inflammatory markers (adiponectin, TNF-alpha, and high sensitivity-CRP), and insulin resistance (QUICKI). RESULTS: No significant changes were observed in study outcomes in subjects treated with placebo. By contrast, when compared with baseline values, subjects treated with n-3 PUFA had significant improvement in FMD (9.1+/-5.8% vs. 11.7+/-4.4%, p=0.02) that was accompanied by decreased plasma triglycerides (117+/-73mg/dl vs. 86+/-44mg/dl, p=0.001) and TNF-alpha levels (8.9+/-2.3pg/ml vs. 6.8+/-2.7pg/ml, p=0.001), and a trend towards increased plasma adiponectin levels (7.8+/-4.5microg/ml vs. 9.5+/-5.1microg/ml, p=0.09). When data were analyzed by multiple regression analysis, decreased TNF-alpha after treatment with n-3 PUFA predicted increased FMD. CONCLUSION: Dietary supplementation with n-3 PUFA significantly improved endothelial function and reduced pro-inflammatory markers in OPDs. Thus, fish oil consumption may have beneficial cardiovascular and metabolic health effects in otherwise healthy subjects predisposed to diabetes and its vascular complications.