Endothelial function, insulin action and cardiovascular risk factors in young healthy adult offspring of parents with Type 2 diabetes: effect of vitamin E in a randomized double-blind, controlled clinical trial.

BACKGROUND AND AIMS: Endothelial dysfunction, insulin resistance and oxidative stress are believed to be central and associated mechanisms in atherogenesis. We aimed to determine the effect of the antioxidant vitamin E on endothelial function, insulin action and cardiovascular risk markers in young healthy adult offspring of parents with Type 2 diabetes. METHODS: Healthy, glucose-tolerant adults (18-38 years), 14 (12 male/2 female) with at least one parent with Type 2 diabetes, and 14 (12 male/2 female) subjects with no family history of diabetes (controls) were studied. Insulin action was assessed by euglycaemic hyperinsulinaemic clamp (1 mU/kg/min). Endothelial function was assessed by forearm blood flow (FBF) responses to intra-brachial artery infusions of acetylcholine (ACh) (endothelium-dependent vasodilation), sodium nitroprusside (SNP) (endothelium-independent vasodilation) and N(G)-monomethyl L-arginine (LNMMA) (nitric oxide synthase inhibition). Thirteen offspring (18-38 years, 11 male/2 female, BMI < 30 kg/m2) completed a randomized, double-blind, crossover trial (12 weeks vitamin E 800 IU/day or placebo, 6-week washout). RESULTS: Exogenous glucose infusion rates to maintain euglycaemia were positively associated with response to acetylcholine in offspring (r = 0.61, P < 0.05), and were linked with triglycerides. Vitamin E had no effect on endothelial function, insulin action or cardiovascular risk markers in healthy adult offspring of parents with Type 2 diabetes. CONCLUSIONS: Our results support a positive association between insulin action and endothelial-dependent vasodilation in young healthy adult offspring of parents with Type 2 diabetes, but indicate no effect of vitamin E on these parameters.

Vitamin C improves endothelial function in healthy estrogen-deficient postmenopausal women.

OBJECTIVE: Estrogen deficiency is associated with increased cardiovascular risk and endothelial dysfunction. Improvements in endothelial function with antioxidants, including vitamin C, have been reported. We aimed to determine the acute effect of vitamin C on endothelial function in healthy women with established menopause. SUBJECTS: Subjects (aged 47-59 years) were at least 1 year postmenopause. Ten (serum estradiol < 50 pmol/l) were not receiving hormone replacement therapy, while eight hysterectomized subjects received subcutaneous estradiol. DESIGN: Forearm blood flow (FBF; strain-gauge plethysmography) responses to intrabrachial artery infusions of incremental doses of acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation) were determined at baseline, and following 1.5 g vitamin C given intravenously. RESULTS: At baseline, estrogen-treated subjects had a lower index of insulin resistance (homeostasis model assessment, HOMA) and lower fibrinogen than those of estrogen deficient subjects. There was a trend towards higher baseline FBF and larger baseline FBF response to acetylcholine in estrogen-treated subjects. FBF responses to acetylcholine were significantly enhanced after vitamin C in estrogen-deficient subjects (area under the dose-response curve (AUC): estrogen-deficient 9.9 +/- 2.6 vs. 15.1 +/- 3.2 (mean +/- SEM), p = 0.02; estrogen-treated 17.0 +/- 2.9 vs. 21.0 +/- 3.2, p = 0.07). Resting FBF and response to sodium nitroprusside were unchanged in either group by vitamin C. Plasminogen activator inhibitor-1 levels fell after vitamin C in the estrogen-deficient group (17.0 +/- 1.6 vs. 14.7 +/- 0.9 IU/ml, p = 0.03). CONCLUSIONS: These results indicate that endothelial function may be improved acutely by antioxidant treatment in postmenopausal women with established estrogen deficiency.