Effect of oral vitamin E (alpha-tocopherol) supplementation on vascular endothelial function in Type 2 diabetes mellitus. Oral L-arginine and vitamins E and C improve endothelial function in women with type 2 diabetes Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels. Uric Acid Restores Endothelial Function in Patients With Type 1 Diabetes and Regular Smokers A randomised controlled trial evaluating the impact of targeted vitamin D supplementation on endothelial function in type 2 diabetes mellitus: The DIMENSION trial Oral antioxidant therapy improves endothelial function in Type 1 but not Type 2 diabetes mellitus. Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes. Supplementation with vitamins C and E improves arterial stiffness and endothelial function in essential hypertensive patients. The Diabetes and Pre-eclampsia Intervention Trial. Food selection based on high total antioxidant capacity improves endothelial function in a low cardiovascular risk population. Vitamin D 20,000 IU per Week for Five Years Does Not Prevent Progression From Prediabetes to Diabetes. 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.
AIMS Vascular endothelial dysfunction , an early marker of atherosclerosis , has been demonstrated in Type 2 diabetes mellitus ( DM ) .  Vitamin E preserves endothelial function in animal models of diabetes and reduces cardiovascular risk . We examined endothelial function and the effect of vitamin E supplements in uncomplicated Type 2 DM . METHODS Forty-eight subjects with Type 2 DM and 21 controls had endothelial function assessed using forearm venous occlusion plethysmography with endothelium-independent ( sodium nitroprusside ) and dependent ( acetylcholine , bradykinin ) vasodilators . Those with diabetes received 1600 i.u . daily oral alpha-tocopherol or placebo , double-blind for 8 weeks , and had endothelial function reassessed . RESULTS The diabetic group had higher HbA1c ( 6.9+/-1.4 vs 4.8+/-0.6 % ; P<0.01 ) and systolic ( 145+/-15 vs. 130+/-16 mm Hg ; P<0.01 ) but not diastolic blood pressure ( 79+/-8 vs. 76+/-9 mm Hg ; P = 0.15 ) . There was blunted vasodilation to acetylcholine ( 15 microg/min ; P<0.01 ) in subjects with diabetes . Vasodilation to sodium nitroprusside and bradykinin was similar ( all P>0.1 ) . Alpha-tocopherol did not affect vasodilation to nitroprusside ( P>0.1 ) , acetylcholine ( P>0.1 ) or bradykinin ( P>0.1 ) . CONCLUSIONS There may be receptor-specific endothelial dysfunction in subjects with uncomplicated Type 2 DM . This is not improved by treatment with alpha-tocopherol Endothelial dilator function is impaired in people with type 2 diabetes mellitus ( T2DM ) . Prior research indicates that this can be improved with intravenous administration of ascorbate or L-arginine , but whether these agents have this effect when administered by the clinical ly practical oral route is unknown . To investigate this question , 10 premenopausal women with T2DM and 10 healthy , premenopausal , non-diabetic women received , in r and om sequence , a 1-week administration of oral L-arginine ( 9 g daily ) or vitamins E ( 1800 mg ) and C ( 1000 mg ) with an intervening 1-week washout period . Flow-mediated brachial artery dilation ( FMD ) was measured by ultrasonography and forearm blood flow was measured by plethysmography before and following blood pressure cuff-induced forearm ischemia before and after each week of treatment . At baseline , the women with T2DM had lesser FMD responses ( 0.028 ± 0.006 cm vs 0.056 ± 0.008 cm , p , 0.05 ) . Post-ischemic forearm hyperemia was reduced at baseline in T2DM compared with controls ( 16.4 ± 1.8 vs 26.0 ± 1.4 ml 100 ml- 1 min- 1 , p < 0.05 ) . Administration of L-arginine caused a 50 ± 12 % increase in FMD in T2DM ( p < 0.05 ) and raised post-ischemic forearm blood flow by 29 ± 8 % ( p < 0.05 ) . No significant changes were seen in controls . Administration of vitamins E and C in women with T2DM produced an increase in the brachial artery diameter response of 79 ± 15 % ( p < 0.05 ) , but did not significantly increase the hyperemic blood flow response ( p = NS ) . No significant changes in the responses of controls from pre to post vitamin administration were observed . We concluded that administration of two types of oral agents improved measures of endothelial function in people with T2DM AIMS To test whether a single large dose of vitamin D2 can improve endothelial function in patients with Type 2 diabetes mellitus and low serum 25-hydroxyvitamin D levels . METHODS Double-blind , parallel group , placebo-controlled r and omized trial . A single dose of 100,000 IU vitamin D2 or placebo was administered to patients with Type 2 diabetes over the winter , when levels of circulating 25-hydroxyvitamin D were likely to be lowest . Patients were enrolled if their baseline 25-hydroxyvitamin D level was < 50 nmol/l .  Endothelial function and blood pressure were measured and fasting blood sample s were taken at baseline and 8 weeks after administration of vitamin D. RESULTS Forty-nine per cent of subjects screened had 25-hydroxyvitamin D levels < 50 nmol/l . Thirty-four subjects completed the study , with a mean age of 64 years and a baseline 25-hydroxyvitamin D level of 38.3 nmol/l .  Vitamin D supplementation  increased 25-hydroxyvitamin D levels by 15.3 nmol/l relative to placebo and significantly improved flow mediated vasodilatation ( FMD ) of the brachial artery by 2.3 % . The improvement in FMD remained significant after adjusting for changes in blood pressure .  Vitamin D supplementation significantly decreased systolic blood pressure by 14 mmHg compared with placebo ; this did not correlate with change in FMD . CONCLUSIONS Vitamin D insufficiency is common in patients with Type 2 diabetes during winter in Scotl and . A single large dose of oral vitamin D2 improves endothelial function in patients with Type 2 diabetes and vitamin D insufficiency Endothelial dysfunction is a characteristic finding in both patients with type 1 diabetes and in regular smokers and is an important precursor to atherosclerosis . The urate molecule has antioxidant properties , which could influence endothelial function . The impact of acutely raising uric acid concentrations on endothelial function was studied in eight men with type 1 diabetes , eight healthy regular smokers , and eight age-matched healthy control subjects in a r and omized , four-way , double-blind , placebo-controlled study . Subjects received 1,000 mg uric acid i.v . in vehicle , 1,000 mg vitamin C as a control antioxidant , vehicle alone , or 0.9 % saline on separate occasions over 1 h. Forearm blood flow responses to intrabrachial acetylcholine and sodium nitroprusside were assessed using venous occlusion plethysmography . Responses to  acetylcholine  , but not sodium nitroprusside , were impaired in patients with diabetes ( P < 0.001 ) and in smokers ( P < 0.005 ) compared with control subjects . Administration of uric acid and vitamin C selectively improved acetylcholine responses in patients with type 1 diabetes ( P < 0.01 ) and in regular smokers ( P < 0.05 ) . Uric acid administration improved endothelial function in the forearm vascular bed of patients with type 1 diabetes and smokers , suggesting that high uric acid concentrations in vivo might serve a protective role in these and other conditions associated with increased cardiovascular risk We sought to determine if vitamin D supplementation , to target 25(OH)D concentrations of 30–40 ng/mL , improves endothelial function in Singapore ’s multi-ethnic type 2 diabetes mellitus population . We r and omised 64 type 2 diabetes mellitus patients with hypovitaminosis D to cholecalciferol 4000 International Unit/matching placebo [ baseline 25(OH)D < 20 ng/mL ] or cholecalciferol 2000 International Unit/matching placebo [ baseline 25(OH)D : 20–30 ng/mL ] daily for 16 weeks with a down titration at 8 weeks if 25(OH)D > 30 ng/mL. Endothelial function was assessed by peripheral tonometry ( reactive hyperaemia index – endothelial peripheral arterial tonometry ) and vascular biomarkers : E-selectin , von-Willebr and factor and high-sensitivity C-reactive protein . We compared the change from baseline parameters in the two groups using Student ’s t-test or Kruskal – Wallis test . A log-normal multivariate regression analysis was used to adjust for relevant baseline variables . The median reactive hyperaemia index in the vitamin D group increased from 0.65 ( interquartile range : 0.42 ) to 0.73 ( interquartile range : 0.36 ) , whereas it decreased from 0.73 ( interquartile range : 0.65 ) to 0.65 ( interquartile range : 0.38 ) ( p = 0.02 ) in the placebo group . After adjustment for baseline variables , the change was not statistically significant for reactive hyperaemia index ( p = 0.07 ) and for other vascular biomarkers ( p > 0.05 ) . Targeted vitamin D supplementation for 16 weeks result ed in a small but non-significant improvement in endothelial function in a type 2 diabetes mellitus cohort Oxidative stress decreases the bioavailability of endothelium-derived nitric oxide in diabetic patients . We investigated whether impaired endothelium-dependent vasodilation ( EDV ) in diabetes can be improved by long-term administration of oral antioxidants .  Forty-nine diabetic subjects [ 26 Type 1 ( T1 ) and 23 Type 2 ( T2 ) ] and 45 matched healthy control subjects were r and omized to receive oral vitamin C ( 1,000 mg ) and vitamin E ( 800 IU ) daily or matching placebo for 6 mo . Vascular ultrasonography was used to determine brachial artery EDV and endothelium-independent vasodilation ( EIV ) . EDV was decreased in both T1 ( 4.9 + /- 0.9 % , P = 0.015 ) and T2 ( 4.1 + /- 1.0 % , P < 0.01 ) subjects compared with control subjects ( 7.7 + /- 0.7 % ) . EIV was decreased in T2 ( 15.0 + /- 1.2 % , P < 0.01 ) but not T1 subjects ( 18.5 + /- 2.3 % , P = 0.3 ) compared with controls ( 21.8 + /- 1.8 % ) . Administration of antioxidant vitamins increased EDV in T1 ( by 3.4 + /- 1.4 % , P = 0.023 ) but not T2 subjects ( by 0.5 . + /- 0.4 % , P = 0.3 ) . Antioxidant therapy had no significant affect on EIV .  Oral antioxidant therapy improves EDV in T1 but not T2 diabetes . These results are consistent with the lack of clinical benefit in studies that have included primarily T2 diabetic patients BACKGROUND Suboptimal vitamin D status is associated with endothelial dysfunction and an increased risk of cardiovascular diseases but it is unclear whether vitamin D supplementation is beneficial . The aim was to investigate the effect of vitamin D supplementation on endothelial function in patients with type 2 diabetes mellitus ( DM ) . METHODS In a double-blind , placebo-controlled trial , we r and omized 100 type 2 DM patients to vitamin D supplement  ( 5000 IU/day , n = 50 ) or placebo ( controls , n = 50 ) for 12 weeks . Assessment of vascular function with brachial artery flow-mediated dilatation ( FMD ) , circulating levels of endothelial progenitor cells ( EPCs ) and brachial-ankle pulse wave velocity , and metabolic parameter , high-sensitivity C-reactive protein ( hsCRP ) and oxidative stress markers were performed before and after the supplementation . RESULTS After 12 weeks , vitamin D treated patients had significant increases in serum 25-hydroxyvitamin D [ 25(OH)D ] concentration ( treatment effect 34.7 ng/mL , 95 % CI 26.4 - 42.9 , P < 0.001 ) and serum ionized calcium ( treatment effect 0.037 mmol/L , 95 % CI 0.007 - 0.067 , P = 0.018 ) ; decreased serum parathyroid hormone concentration ( treatment effect -0.55 pmol/L , 95 % CI -1.08 to -0.02 , P = 0.042 ) compared to patients who received placebo . Nevertheless , vitamin D supplementation did not improve vascular function as determined by FMD , circulating EPC count or baPWV ( all P > 0.05 ) . Furthermore , hsCRP , oxidative stress markers , low- and high-density lipoprotein and glycated hemoglobin were also similar between two groups ( all P > 0.05 ) . CONCLUSION In patients with type 2 DM , 12 weeks oral supplementation of vitamin D did not significantly affect vascular function or serum biomarkers of inflammation and oxidative stress . CLINICAL TRIAL NUMBER HKCTR-867 , www.hk clinical trials.com BACKGROUND Essential hypertension is characterized by endothelial dysfunction , arterial stiffness , and increased oxidative stress . We evaluated the effect of short-term combined treatment with the antioxidants vitamins C and E on endothelial function , arterial stiffness , and oxidative stress in untreated essential hypertensive patients . METHODS A r and omized , double-blind , placebo-controlled , crossover study design was used to assign 30 male essential hypertensive patients to either vitamin C ( 1 g ) and vitamin E ( 400 IU ) or placebo for 8 weeks . Endothelium-dependent response was assessed as flow-mediated dilation ( FMD ) of the brachial artery . Arterial stiffness was assessed as central pulse wave velocity ( PWV ) and augmentation index ( AIx ) . Plasma markers of oxidative stress and antioxidant status were measured . RESULTS After vitamin supplementation , FMD was significantly improved . Central PWV was significantly reduced , while AIx tended to decrease . Plasma vitamin levels and antioxidant capacity increased significantly . Levels of oxidative stress decreased . Changes in central PWV were related to changes in levels of oxidative stress . CONCLUSIONS Combined treatment with vitamins C and E has beneficial effects on endothelium-dependent vasodilation and arterial stiffness in untreated , essential hypertensive patients . This effect is associated with changes in plasma markers of oxidative stress OBJECTIVE Rates of  pre-eclampsia  in women with type 1 diabetes are two to four times higher than in normal pregnancies . Diabetes is associated with antioxidant depletion and increased free radical production , and an increasing body of evidence suggests that oxidative stress and endothelial cell activation may be relevant to disease pathogenesis in pre-eclampsia . The Diabetes and Pre-eclampsia Intervention Trial ( DAPIT ) aims to establish if pregnant women with type 1 diabetes supplemented with vitamins C and E have lower rates of pre-eclampsia and endothelial activation compared with placebo treatment . METHODS DAPIT is a r and omised multicentre double-blind placebo-controlled trial that will recruit 756 pregnant women with type 1 diabetes from 20 metabolic-antenatal clinics in the UK over 4 years . Women are r and omised to daily vitamin C ( 1000 mg ) and vitamin E ( 400 IU ) or placebo at 8 - 22 weeks of gestation until delivery . Maternal venous blood is obtained at r and omisation , 26 and 34 weeks , for markers of endothelial activation and oxidative stress and to assess glycaemic control . The primary outcome of DAPIT is pre-eclampsia . Secondary outcomes include endothelial activation ( PAI-1/PAI-2 ) and birthweight centile BACKGROUND AND AIMS Oxidative stress has been advocated as a major cause for cardiovascular disease ( CVD ) , and low plasma antioxidant concentrations are associated with endothelial dysfunction , the first step towards atherosclerosis . However , although the antioxidant content in fruits and vegetables may explain at least in part their protective effect against CVD , supplementation with antioxidant vitamins fails to improve endothelial function and reduce CVD risk . The aim of this study was to investigate the impact of a diet rich in antioxidants on endothelial function measured by flow-mediated dilatation ( FMD ) in volunteers at low cardiovascular risk . METHODS AND RESULTS In a crossover trial , 24 subjects ( 13 women , mean age 61 ± 3 years ) , received , in a r and omised order , a 14-day high ( HT ) and a 14-day low ( LT ) antioxidant diets , with a 2-week wash-out ( WO ) in between . Both diets were comparable in daily portions of fruits and vegetables , and in alcohol , fibre and macronutrient intake , but differed in their total antioxidant capacity . Before and after each diet , anthropometrics , blood pressure , fasting plasma glucose , lipid profile , hepatic enzymes , circulating antioxidant concentrations , high sensitivity C-reactive protein ( hs-CRP ) and FMD were assessed . FMD increased significantly during the HT diet compared to the LT ( p < 0.000 ) . FMD values were 2.3 % higher after HT compared with LT ( p < 0.001 ) after adjustment for age , gender and diet order . α-tocopherol increased significantly ( p < 0.05 ) and hs-CRP and of γ-glutamyltranspeptidase decreased significantly ( p < 0.05 and p < 0.01 , respectively ) during the HT diet , compared with the LT diet . CONCLUSIONS A short-term HT diet improves endothelial function in volunteers at low cardiovascular risk , which may further reduce their risk of CVD CONTEXT Vitamin D deficiency is associated with insulin resistance and risk of future diabetes . OBJECTIVE The objective of the study was to test whether supplementation with vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes mellitus ( T2DM ) . DESIGN This was a r and omized controlled trial performed in 2008 through 2015 . SETTING The study was conducted at the clinical research unit at a teaching hospital . PATIENTS Five hundred eleven subjects ( mean age 62 y , 314 males ) with prediabetes diagnosed with an oral glucose tolerance test as part of the Tromsø Study 2007–2008 were included . A total of 256 were r and omized to vitamin D and 255 to placebo .  Twenty-nine subjects in the vitamin D and 24 in the placebo group withdrew because of adverse events . INTERVENTIONS Interventions included vitamin D ( cholecalciferol ) 20 000 IU/wk vs placebo for 5 years . Annual oral glucose tolerance tests were performed . MAIN OUTCOME MEASURE Progression to T2DM was the main outcome measure . Secondary outcomes were change in glucose levels , insulin resistance , serum lipids , and blood pressure . RESULTS The mean baseline serum 25-hydroxyvitamin D level was 60 nmol/L ( 24 ng/mL ) . One hundred three in the vitamin D and 112 in the placebo group developed T2DM ( hazard risk 0.90 ; 95 % confidence interval 0.69–1.18 , Cox regression , P = .45 , intention to treat analysis ) . No consistent significant effects on the other outcomes were seen . Subgroup analyses in subjects with low baseline 25-hydroxyvitamin D yielded similar results . No serious side effects related to the intervention were recorded . CONCLUSIONS In subjects without vitamin D deficiency , vitamin D supplementation is unlikely to prevent progression from prediabetes to diabetes . Very large studies with inclusion of vitamin D-deficient subjects will probably be needed to show such a putative effect . This study tested if supplementation with  vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes ( T2DM ) BACKGROUND AND AIMS Endothelial dysfunction , insulin resistance and oxidative stress are believed to be central and associated mechanisms in atherogenesis . We aim ed 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 r and omized , 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
Prolonged antioxidant vitamin E and /or C supplementation could be effective to improve endothelial function in non-obese T2DM subjects
Controversy exists among trials assessing whether prolonged antioxidant vitamin supplementation improves endothelial function in type 2 diabetes mellitus ( T2DM ) subjects .
The aim of this study was to systematic ally review and quantify the effect of antioxidant vitamin supplementation on endothelial function in T2DM subjects .