human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Vascular disease accounts for the majority of the clinical complications in diabetes mellitus . As an exaggerated oxidative stress degree has been postulated as the link between diabetes mellitus and endothelial function , a possible positive effect of plasma vitamin E ( Vit . E ) administration on brachial reactivity could be postulated . Our study aims at investigating the possible effect of chronic Vit . E administration on brachial reactivity , oxidative stress indexes , and intracellular magnesium and calcium content in type II diabetic patients free of diabetic complications . Forty adult , type II diabetic patients were enrolled in the study , which was deigned as a double blind , r and omized vs. placebo trial . At baseline all patients underwent the following tests : 1 ) anthropometric and metabolic examinations , 2 ) evaluation of oxidative stress indexes , 3 ) intracellular magnesium and calcium measurements , and 4 ) determination of arterial compliance and distensibility . Then , all patients were r and omly assigned to Vit . E treatment at a dose of 600 mg/day ( Evion Forte ; n = 20 ) or placebo ( n = 20 ) over 8 weeks . At the end of this treatment period , a complete reevaluation of the patients was made . Vit . E treatment was associated with a significant improvement in the percent change in brachial artery diameter ( P<0.03 ) and oxidative stress indexes ( P < 0.005 ) . In the Vit . E group , the percent change in brachial artery diameter correlated positively with the percent change in oxidative stress indexes ( oxidized/reduced glutathione , Trolox-equivalent antioxidant capacity , thiobarbituric acid reaction products , lipid peroxides ) and intracellular cation content ( magnesium and calcium ) . After adjustment for age , sex , body mass index , and wait/hip ratio , all of these correlations remained significant ( P<0.03 for all ) . Furthermore , adjusting for glycosylated hemoglobin , plasma total cholesterol , and homeostatic model index , brachial artery diameter was still correlated with the percent change in oxidative stress indexes ( P<0.04 for all ) . Nevertheless , the relationship between the percent change in brachial artery diameter and oxidative stress indexes was no longer significant after adjustment for intracellular Mg and Ca2 + . In conclusion , our study demonstrates that chronic administration of Vit . E improves brachial artery reactivity in patients with type II diabetes mellitus . Such an effect seems mediated by a reduction in oxidative stress and a regulation of intracellular calcium and magnesium contents Manifestations of vascular disease , including microvascular changes , constitute the major part of the morbidity and mortality in diabetic patients . Oxidative stress has been suggested to play an important role in the vascular dysfunction of diabetic patients . Furthermore , epidemiological observations indicate a beneficial effect of an increased dietary intake of antioxidants . The present study tested the hypothesis that the antioxidant ascorbic acid influences microcirculatory function in patients with Type II diabetes . Patients with Type II diabetes were treated with 1 g of ascorbic acid three times a day for 2 weeks in a r and omized placebo-controlled double-blind cross-over design . Microvascular reactivity was assessed by  vital capillaroscopy  and PRH ( post-occlusive reactive hyperaemia ) . hs-CRP ( high-sensitivity C-reactive protein ) , IL-6 ( interleukin-6 ) , IL-1ra ( interleukin-1 receptor antagonist ) and ox-LDL ( oxidized low-density lipoprotein ) were analysed . The results showed no significant change in microvascular reactivity assessed after 2 weeks of ascorbic acid treatment . TtP ( time to peak ) was 12.0+/-3.3 s before and 11.2+/-3.5 s after ascorbic acid ( n=17 ) . In comparison , TtP was 11.5+/-2.9 s before and 10.6+/-2.8 s after placebo ( not significant ) . IL-1ra , IL-6 , hs-CRP and ox-LDL did not change significantly after ascorbic acid , neither as absolute or relative values . In conclusion , in contrast with some studies reported previously , we could not demonstrate an effect of continuous oral treatment with ascorbic acid on microvascular reactivity assessed at the level of individual capillaries . Furthermore , we found no indication of an effect on inflammatory cytokines or ox-LDL Endothelial dysfunction is a hallmark of Type 2 diabetes related to hyperglycemia and oxidative stress . Nitric oxide-dependent vasodilator actions of insulin may augment glucose disposal . Thus endothelial dysfunction may worsen insulin resistance . Intra-arterial administration of vitamin C improves endothelial dysfunction in diabetes . In the present study , we investigated effects of high-dose oral vitamin C to alter endothelial dysfunction and insulin resistance in Type 2 diabetes .  Plasma vitamin C levels in 109 diabetic subjects were lower than healthy ( 36 + /- 2 microM ) levels . Thirty-two diabetic subjects with low plasma vitamin C ( < 40 microM ) were subsequently enrolled in a r and omized , double-blind , placebo-controlled study of vitamin C ( 800 mg/day for 4 wk ) . Insulin sensitivity ( determined by glucose clamp ) and forearm blood flow in response to ACh , sodium nitroprusside ( SNP ) , or insulin ( determined by plethysmography ) were assessed before and after 4 wk of treatment . In the placebo group ( n = 17 subjects ) , plasma vitamin C ( 22 + /- 3 microM ) , fasting glucose ( 159 + /- 12 mg/dl ) , insulin ( 19 + /- 7 microU/ml ) , and SI(Clamp ) [ 2.06 + /- 0.29 x 10(-4 ) dl x kg(-1 ) x min(-1)/(microU/ml ) ] did not change significantly after placebo treatment . In the  vitamin C  group ( n = 15 subjects ) , basal plasma vitamin C ( 23 + /- 2 microM ) increased to 48 + /- 6 microM ( P < 0.01 ) after treatment , but this was significantly less than that expected for healthy subjects ( > 80 microM ) . No significant changes in fasting glucose ( 156 + /- 11 mg/dl ) , insulin ( 14 + /- 2 microU/ml ) , SI(Clamp ) [ 2.71 + /- 0.46 x 10(-4 ) dl x kg(-1 ) x min(-1)/(microU/ml ) ] , or forearm blood flow in response to ACh , SNP , or insulin were observed after vitamin C treatment . We conclude that high-dose oral vitamin C therapy , result ing in incomplete replenishment of vitamin C levels , is ineffective at improving endothelial dysfunction and insulin resistance in Type 2 diabetes OBJECTIVE To examine the effect of vitamin C on forearm vasodilatory response to reactive hyperemia and on plasma level of plasminogen activator inhibitor 1 ( PAI-1 ) , von Willebr and factor ( vWF ) , tissue plasminogen activator ( tPA ) , antithrombin III ( ATIII ) , proteins C and S , and factors V ( fV ) and VII ( fVII ) in patients with both type 2 diabetes and CAD . RESEARCH DESIGN AND METHODS A total of 39 patients with type 2 diabetes and CAD were divided into two groups and received vitamin C ( 2 g/day ) or no antioxidant for 4 weeks . Forearm blood flow was determined using venous occlusion gauge-strain plethysmography at baseline and after treatment . Forearm vasodilatory response to reactive hyperemia ( RH% ) or nitrate ( NTG% ) was defined as the percent change of flow from baseline to the maximum flow during reactive hyperemia or after administration of nitrate , respectively . Biochemical markers were determined by enzyme-linked immunosorbent assay ( ELISA ) or other st and ard methods . RESULTS RH% was significantly increased after treatment with vitamin C ( from 62.4 + /- 7.2 to 83.1 + /- 9.3 % , P = 0.024 ) but remained unaffected in the control group . Vitamin C decreased plasma levels of fV ( from 143 + /- 5.4 to 123 + /- 6.03 % , P = 0.038 ) , vWF ( from 133.5 + /- 14.5 to 109.5 + /- 11.4 % , P = 0.016 ) , and tPA ( from 12.3 + /- 0.99 to 8.40 + /- 0.60 ng/ml , P = 0.001 ) , whereas these levels remained unaffected in the control group . The changes in RH% , vWF , and tPA were significantly greater ( P = 0.028 , 0.036 , and 0.007 , respectively ) in the vitamin C-treated group than in the control group . Levels of ATIII , proteins S and C , fVII , and PAI-1 remained unchanged in all groups . CONCLUSIONS Short-term treatment with high doses of vitamin C improved RH% and decreased plasma levels of tPA and vWF in patients with type 2 diabetes and CAD We examined the effects of high-dosage vitamin E treatment over a 12-month period on the vascular reactivity of micro- and macrocirculation and left ventricular function in diabetic patients . Subjects ( n = 89 ) were r and omized to vitamin E ( 1,800 IU daily ) or placebo and were followed for 12 months . High-resolution ultrasound images were used to measure the flow-mediated dilation ( FMD ; endothelium dependent ) and nitroglycerin-induced dilation ( NID ; endothelium independent ) of the brachial artery . Laser Doppler perfusion imaging was used to measure vascular reactivity in the forearm skin . Left ventricular function was evaluated using transthoracic echocardiogram . At the end of the 6-month period , a worsening in endothelium-dependent skin vasodilation ( P = 0.02 ) and rise in endothelin levels ( P = 0.01 ) were found in the vitamin E compared with the placebo group . At the end of the 12-month period , a worsening was observed in NID ( P = 0.02 ) and a marginal worsening was seen in systolic blood pressure ( P = 0.04 ) and FMD ( P = 0.04 ) in the vitamin E compared with the placebo group . In addition C-reactive protein levels decreased marginally in the vitamin E compared with the placebo group ( P = 0.05 ) . No changes were observed in left ventricular function . We concluded that long-term treatment with 1,800 IU of vitamin E has no beneficial effects on endothelial or left ventricular function in diabetic patients . Because vitamin E-treated patients had a worsening in some vascular reactivity measurements when compared with control subjects , the use of high dosages of vitamin E can not be recommended The aims of the study were to evaluate the short-term effects of a new thermosensitive , vitamin E ( V-E ) mousse on local free radicals ( FR ) and skin flux in diabetic microangiopathy . A group of 40 patients with diabetic microangiopathy was included . The variation in measure ments of skin FR was evaluated by the D-Rom test . Subjects were between 45 and 65 years with type II diabetes and good metabolic control .  E-mousse ® , a thermoactive preparation of acetate vitamin E ( 20 % ) , was applied twice daily on the whole surface of the leg ( below knee ) and foot for 3 weeks . The contralateral leg was untreated acting as control .  Subjects with age between 45 and 65 years with type II diabetes ( diagnosed at least 5 years before ) and good metabolic control ( blood sugar < 180 mg/dL ) were included after informed consent . Patients with uncontrolled diabetes , peripheral vascular disease , and severe lower limbs infec tions were excluded .  Local free radicals ( FR ) and laser Doppler flux including the venoarteriolar response ( VAR ) were evaluated . The tolerability was evaluated by a semiquantitative score . Of the 40 included patients 34 completed the study . The 2 groups were comparable . At 3 weeks there was no decrease in FR in controls ; the decrease in the treatment group was 45.3 % ( p < 0.05 ) . Also in the treatment group RF decreased ( p < 0.05 ) and the VARveno improved from an average of 21 % to an average of 38 % ( p < 0.05 ) . No significant variations were observed in the control group . The variation in symptomatic score was from a total value of 8 to 5 in the control group and from 8 to 1 in the treatment group ( p < 0.02 ) . Their tolerability was good . In conclusion local treatment with E-mousse for 3 weeks in diabetic microangiopathy improves skin microcirculation and the metabolic condition as shown by the decrease in FR BACKGROUND Insulin therapy may influence cardiovascular disease ( CVD ) and lipid metabolism in type 2 diabetes ( T2D ) . Exaggerated postpr and ial 
    Output:
    
agent
Prolonged antioxidant vitamin E and /or C supplementation could be effective to improve endothelial function in non-obese T2DM subjects
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Vascular disease accounts for the majority of the clinical complications in diabetes mellitus . As an exaggerated oxidative stress degree has been postulated as the link between diabetes mellitus and endothelial function , a possible positive effect of plasma vitamin E ( Vit . E ) administration on brachial reactivity could be postulated . Our study aims at investigating the possible effect of chronic Vit . E administration on brachial reactivity , oxidative stress indexes , and intracellular magnesium and calcium content in type II diabetic patients free of diabetic complications . Forty adult , type II diabetic patients were enrolled in the study , which was deigned as a double blind , r and omized vs. placebo trial . At baseline all patients underwent the following tests : 1 ) anthropometric and metabolic examinations , 2 ) evaluation of oxidative stress indexes , 3 ) intracellular magnesium and calcium measurements , and 4 ) determination of arterial compliance and distensibility . Then , all patients were r and omly assigned to Vit . E treatment at a dose of 600 mg/day ( Evion Forte ; n = 20 ) or placebo ( n = 20 ) over 8 weeks . At the end of this treatment period , a complete reevaluation of the patients was made . Vit . E treatment was associated with a significant improvement in the percent change in brachial artery diameter ( P<0.03 ) and oxidative stress indexes ( P < 0.005 ) . In the Vit . E group , the percent change in brachial artery diameter correlated positively with the percent change in oxidative stress indexes ( oxidized/reduced glutathione , Trolox-equivalent antioxidant capacity , thiobarbituric acid reaction products , lipid peroxides ) and intracellular cation content ( magnesium and calcium ) . After adjustment for age , sex , body mass index , and wait/hip ratio , all of these correlations remained significant ( P<0.03 for all ) . Furthermore , adjusting for glycosylated hemoglobin , plasma total cholesterol , and homeostatic model index , brachial artery diameter was still correlated with the percent change in oxidative stress indexes ( P<0.04 for all ) . Nevertheless , the relationship between the percent change in brachial artery diameter and oxidative stress indexes was no longer significant after adjustment for intracellular Mg and Ca2 + . In conclusion , our study demonstrates that chronic administration of Vit . E improves brachial artery reactivity in patients with type II diabetes mellitus . Such an effect seems mediated by a reduction in oxidative stress and a regulation of intracellular calcium and magnesium contents Manifestations of vascular disease , including microvascular changes , constitute the major part of the morbidity and mortality in diabetic patients . Oxidative stress has been suggested to play an important role in the vascular dysfunction of diabetic patients . Furthermore , epidemiological observations indicate a beneficial effect of an increased dietary intake of antioxidants . The present study tested the hypothesis that the antioxidant ascorbic acid influences microcirculatory function in patients with Type II diabetes . Patients with Type II diabetes were treated with 1 g of ascorbic acid three times a day for 2 weeks in a r and omized placebo-controlled double-blind cross-over design . Microvascular reactivity was assessed by  vital capillaroscopy  and PRH ( post-occlusive reactive hyperaemia ) . hs-CRP ( high-sensitivity C-reactive protein ) , IL-6 ( interleukin-6 ) , IL-1ra ( interleukin-1 receptor antagonist ) and ox-LDL ( oxidized low-density lipoprotein ) were analysed . The results showed no significant change in microvascular reactivity assessed after 2 weeks of ascorbic acid treatment . TtP ( time to peak ) was 12.0+/-3.3 s before and 11.2+/-3.5 s after ascorbic acid ( n=17 ) . In comparison , TtP was 11.5+/-2.9 s before and 10.6+/-2.8 s after placebo ( not significant ) . IL-1ra , IL-6 , hs-CRP and ox-LDL did not change significantly after ascorbic acid , neither as absolute or relative values . In conclusion , in contrast with some studies reported previously , we could not demonstrate an effect of continuous oral treatment with ascorbic acid on microvascular reactivity assessed at the level of individual capillaries . Furthermore , we found no indication of an effect on inflammatory cytokines or ox-LDL Endothelial dysfunction is a hallmark of Type 2 diabetes related to hyperglycemia and oxidative stress . Nitric oxide-dependent vasodilator actions of insulin may augment glucose disposal . Thus endothelial dysfunction may worsen insulin resistance . Intra-arterial administration of vitamin C improves endothelial dysfunction in diabetes . In the present study , we investigated effects of high-dose oral vitamin C to alter endothelial dysfunction and insulin resistance in Type 2 diabetes .  Plasma vitamin C levels in 109 diabetic subjects were lower than healthy ( 36 + /- 2 microM ) levels . Thirty-two diabetic subjects with low plasma vitamin C ( < 40 microM ) were subsequently enrolled in a r and omized , double-blind , placebo-controlled study of vitamin C ( 800 mg/day for 4 wk ) . Insulin sensitivity ( determined by glucose clamp ) and forearm blood flow in response to ACh , sodium nitroprusside ( SNP ) , or insulin ( determined by plethysmography ) were assessed before and after 4 wk of treatment . In the placebo group ( n = 17 subjects ) , plasma vitamin C ( 22 + /- 3 microM ) , fasting glucose ( 159 + /- 12 mg/dl ) , insulin ( 19 + /- 7 microU/ml ) , and SI(Clamp ) [ 2.06 + /- 0.29 x 10(-4 ) dl x kg(-1 ) x min(-1)/(microU/ml ) ] did not change significantly after placebo treatment . In the  vitamin C  group ( n = 15 subjects ) , basal plasma vitamin C ( 23 + /- 2 microM ) increased to 48 + /- 6 microM ( P < 0.01 ) after treatment , but this was significantly less than that expected for healthy subjects ( > 80 microM ) . No significant changes in fasting glucose ( 156 + /- 11 mg/dl ) , insulin ( 14 + /- 2 microU/ml ) , SI(Clamp ) [ 2.71 + /- 0.46 x 10(-4 ) dl x kg(-1 ) x min(-1)/(microU/ml ) ] , or forearm blood flow in response to ACh , SNP , or insulin were observed after vitamin C treatment . We conclude that high-dose oral vitamin C therapy , result ing in incomplete replenishment of vitamin C levels , is ineffective at improving endothelial dysfunction and insulin resistance in Type 2 diabetes OBJECTIVE To examine the effect of vitamin C on forearm vasodilatory response to reactive hyperemia and on plasma level of plasminogen activator inhibitor 1 ( PAI-1 ) , von Willebr and factor ( vWF ) , tissue plasminogen activator ( tPA ) , antithrombin III ( ATIII ) , proteins C and S , and factors V ( fV ) and VII ( fVII ) in patients with both type 2 diabetes and CAD . RESEARCH DESIGN AND METHODS A total of 39 patients with type 2 diabetes and CAD were divided into two groups and received vitamin C ( 2 g/day ) or no antioxidant for 4 weeks . Forearm blood flow was determined using venous occlusion gauge-strain plethysmography at baseline and after treatment . Forearm vasodilatory response to reactive hyperemia ( RH% ) or nitrate ( NTG% ) was defined as the percent change of flow from baseline to the maximum flow during reactive hyperemia or after administration of nitrate , respectively . Biochemical markers were determined by enzyme-linked immunosorbent assay ( ELISA ) or other st and ard methods . RESULTS RH% was significantly increased after treatment with vitamin C ( from 62.4 + /- 7.2 to 83.1 + /- 9.3 % , P = 0.024 ) but remained unaffected in the control group . Vitamin C decreased plasma levels of fV ( from 143 + /- 5.4 to 123 + /- 6.03 % , P = 0.038 ) , vWF ( from 133.5 + /- 14.5 to 109.5 + /- 11.4 % , P = 0.016 ) , and tPA ( from 12.3 + /- 0.99 to 8.40 + /- 0.60 ng/ml , P = 0.001 ) , whereas these levels remained unaffected in the control group . The changes in RH% , vWF , and tPA were significantly greater ( P = 0.028 , 0.036 , and 0.007 , respectively ) in the vitamin C-treated group than in the control group . Levels of ATIII , proteins S and C , fVII , and PAI-1 remained unchanged in all groups . CONCLUSIONS Short-term treatment with high doses of vitamin C improved RH% and decreased plasma levels of tPA and vWF in patients with type 2 diabetes and CAD We examined the effects of high-dosage vitamin E treatment over a 12-month period on the vascular reactivity of micro- and macrocirculation and left ventricular function in diabetic patients . Subjects ( n = 89 ) were r and omized to vitamin E ( 1,800 IU daily ) or placebo and were followed for 12 months . High-resolution ultrasound images were used to measure the flow-mediated dilation ( FMD ; endothelium dependent ) and nitroglycerin-induced dilation ( NID ; endothelium independent ) of the brachial artery . Laser Doppler perfusion imaging was used to measure vascular reactivity in the forearm skin . Left ventricular function was evaluated using transthoracic echocardiogram . At the end of the 6-month period , a worsening in endothelium-dependent skin vasodilation ( P = 0.02 ) and rise in endothelin levels ( P = 0.01 ) were found in the vitamin E compared with the placebo group . At the end of the 12-month period , a worsening was observed in NID ( P = 0.02 ) and a marginal worsening was seen in systolic blood pressure ( P = 0.04 ) and FMD ( P = 0.04 ) in the vitamin E compared with the placebo group . In addition C-reactive protein levels decreased marginally in the vitamin E compared with the placebo group ( P = 0.05 ) . No changes were observed in left ventricular function . We concluded that long-term treatment with 1,800 IU of vitamin E has no beneficial effects on endothelial or left ventricular function in diabetic patients . Because vitamin E-treated patients had a worsening in some vascular reactivity measurements when compared with control subjects , the use of high dosages of vitamin E can not be recommended The aims of the study were to evaluate the short-term effects of a new thermosensitive , vitamin E ( V-E ) mousse on local free radicals ( FR ) and skin flux in diabetic microangiopathy . A group of 40 patients with diabetic microangiopathy was included . The variation in measure ments of skin FR was evaluated by the D-Rom test . Subjects were between 45 and 65 years with type II diabetes and good metabolic control .  E-mousse ® , a thermoactive preparation of acetate vitamin E ( 20 % ) , was applied twice daily on the whole surface of the leg ( below knee ) and foot for 3 weeks . The contralateral leg was untreated acting as control .  Subjects with age between 45 and 65 years with type II diabetes ( diagnosed at least 5 years before ) and good metabolic control ( blood sugar < 180 mg/dL ) were included after informed consent . Patients with uncontrolled diabetes , peripheral vascular disease , and severe lower limbs infec tions were excluded .  Local free radicals ( FR ) and laser Doppler flux including the venoarteriolar response ( VAR ) were evaluated . The tolerability was evaluated by a semiquantitative score . Of the 40 included patients 34 completed the study . The 2 groups were comparable . At 3 weeks there was no decrease in FR in controls ; the decrease in the treatment group was 45.3 % ( p < 0.05 ) . Also in the treatment group RF decreased ( p < 0.05 ) and the VARveno improved from an average of 21 % to an average of 38 % ( p < 0.05 ) . No significant variations were observed in the control group . The variation in symptomatic score was from a total value of 8 to 5 in the control group and from 8 to 1 in the treatment group ( p < 0.02 ) . Their tolerability was good . In conclusion local treatment with E-mousse for 3 weeks in diabetic microangiopathy improves skin microcirculation and the metabolic condition as shown by the decrease in FR BACKGROUND Insulin therapy may influence cardiovascular disease ( CVD ) and lipid metabolism in type 2 diabetes ( T2D ) . Exaggerated postpr and ial 
    Output:
    