title: The Effect of Magnesium Supplementation in Increasing Doses on the Control of Type 2 Diabetes Potential Antioxidant Effects of Zinc and Chromium Supplementation in People with Type 2 Diabetes Mellitus Chromium supplementation shortens QTc interval duration in patients with type 2 diabetes mellitus. Beneficial effects of soy phytoestrogen intake in postmenopausal women with type 2 diabetes. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial. Daily magnesium supplements improve glucose handling in elderly subjects. Supplementation with mixed tocopherols increases serum and blood cell gamma-tocopherol but does not alter biomarkers of platelet activation in subjects with type 2 diabetes. Pharmacologic doses of vitamin E improve insulin action in healthy subjects and non-insulin-dependent diabetic patients. The effects of inorganic chromium and brewer's yeast supplementation on glucose tolerance, serum lipids and drug dosage in individuals with type 2 diabetes. Failure of trivalent chromium to improve hyperglycemia in diabetes mellitus. Influence of chromium-enriched yeast on blood glucose and insulin variables, blood lipids, and markers of oxidative stress in subjects with type 2 diabetes mellitus Ascorbic Acid Reduces Blood Pressure and Arterial Stiffness in Type 2 Diabetes Long term effects of oral vitamin E supplement in type II diabetic patients. Oral vitamin C reduces arterial stiffness and platelet aggregation in humans. Effect of ascorbic acid on microcirculation in patients with Type II diabetes: a randomized placebo-controlled cross-over study. Elevated Intakes of Supplemental Chromium Improve Glucose and Insulin Variables in Individuals With Type 2 Diabetes High-dose oral vitamin C partially replenishes vitamin C levels in patients with Type 2 diabetes and low vitamin C levels but does not improve endothelial dysfunction or insulin resistance. Short-term oral folic acid supplementation enhances endothelial function in patients with type 2 diabetes. Chromium treatment has no effect in patients with poorly controlled, insulin-treated type 2 diabetes in an obese Western population: a randomized, double-blind, placebo-controlled trial. Selenium supplementation decreases nuclear factor-kappa B activity in peripheral blood mononuclear cells from type 2 diabetic patients. Effect of oral vitamin E (alpha-tocopherol) supplementation on vascular endothelial function in Type 2 diabetes mellitus. The breakdown of preexisting advanced glycation end products is associated with reduced renal fibrosis in experimental diabetes. How good a marker is insulin level for insulin resistance? Lack of effect of oral vitamin C on blood pressure, oxidative stress and endothelial function in Type II diabetes. Antidiabetic effect of Pycnogenol French maritime pine bark extract in patients with diabetes type II. The effect of vitamin E on blood pressure in individuals with type 2 diabetes: a randomized, double-blind, placebo-controlled trial Beneficial Effect of Chromium Supplementation on Serum Triglyceride Levels in NIDDM Effect of tocopherol on platelet aggregation in non-insulin-dependent diabetes mellitus: ex vivo and in vitro studies. Effects of Vitamin E on Susceptibility of Low-Density Lipoprotein and Low-Density Lipoprotein Subfractions to Oxidation and on Protein Glycation in NIDDM Vitamin C: an aldose reductase inhibitor that normalizes erythrocyte sorbitol in insulin-dependent diabetes mellitus. Experimental and clinical studies on the reduction of erythrocyte sorbitol-glucose ratios by ascorbic acid in diabetes mellitus. Effects of alpha-tocopherol and mixed tocopherol supplementation on markers of oxidative stress and inflammation in type 2 diabetes. The influence of chromium chloride-containing milk to glycemic control of patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Oral zinc in macular degeneration. [Diabetes mellitus--a free radical-associated disease. Results of adjuvant antioxidant supplementation]. Magnesium and ascorbic acid supplementation in diabetes mellitus.
abstract: OBJECTIVE Hypomagnesemia occurs in 25–38 % of patients with type 2 diabetes . Several studies have suggested an association between magnesium ( Mg ) depletion and insulin resistance and /or reduction of insulin secretion in these cases . Our purpose was to evaluate if Mg supplementation ( as magnesium oxide [ MgO ] ) would improve metabolic control in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS We studied 128 patients with type 2 diabetes ( 32 men , 96 women , aged 30–69 years ) , treated by diet or diet plus oral antidiabetic drugs , in the Bahia Federal University Hospital , Brazil . Patients at risk for hypomagnesemia or with reduced renal function were excluded . This study was a clinical r and omized double-blind placebo-controlled trial . Patients received either placebo , 20.7 mmol MgO , or 41.4 mmol MgO daily(elementary Mg ) for 30 days . Mg concentrations were measured in plasma , in mononuclear cells , and in 24-h urine sample s. Fasting blood glucose , HbA1 , and fructosamine were used as parameters of metabolic control . RESULTS Of the patients , 47.7 % had low plasma Mg , and 31.1 % had low intramononuclear Mg levels . Intracellular Mg in patients with diabetes was significantly lower than in the normal population ( 62 blood donors ; 1.4 ± 0.6 vs. 1.7 ± 0.6 μg/mg of total proteins ) . No correlation was found between plasma and intracellular Mg concentrations ( r = −0.179 ; P = 0.15 ) or between Mg concentrations and glycemic control ( r = −0.165 ; P = 0.12 ) . Intracellular Mg levels were lower in patients with peripheral neuropathy than in those without ( 1.2 ± 0.5 vs. 1.5 ± 0.6 μg/mg ) . Similar findings were observed in patients with coronary disease ( 1.0 ± 0.5 vs. 1.5 ± 0.6 μg/mg ) . In the placebo and in the 20.7 mmol Mg groups , neither a change in plasma and intracellular levels nor an improvement in glycemic control were observed . Replacement with 41.4 mmol Mg tended to increase plasma , cellular , and urine Mg and caused a significant fall ( 4.1 ± 0.8 to 3.8 ± 0.7 mmol/1 ) in fructosamine ( normal , 1.87–2.87 mmol/1 ) . CONCLUSIONS Mg depletion is common in poorly controlled patients with type 2 diabetes , especially in those with neuropathy or coronary disease . More prolonged use of Mg in doses that are higher than usual is needed toestablish its routine or selective administration in patients with type 2 diabetes to improve control or prevent chronic complications Objective : To determine the effects of combined zinc ( Zn ) and chromium ( Cr ) supplementation on oxidative stress and glucose homeostasis of people with type 2 diabetes . Design : Tunisian adult subjects with HbA1C > 7.5 % were supplemented for 6 months with 30 mg/d of Zn as Zn gluconate or 400 μg/d of Cr as Cr pidolate or combined Zn/Cr supplementation or placebo . The effects of supplementation on plasma zinc ( Zn ) , copper ( Cu ) , selenium ( Se ) , urinary Zn , Cr , plasma thiobarbituric acid reactive substances ( TBARS ) , Cu-Zn superoxide dismutase ( SOD ) and Se glutathione peroxidase ( GPx ) in red blood cells , blood lipids and lipoproteins , HbA1C and fasting glucose were measured at the beginning of the study and after six months . Results : At the beginning of the study , more than 30 % of the subjects may have been Zn deficient with plasma Zn values less than 10.7 μmol/L , whereas levels of plasma Cu , Se and antioxidant RBC enzyme activities were in the normal ranges . Following supplementation , there were significant decreases of plasma TBARS in the Cr ( 13.6 % ) , Zn ( 13.6 % ) and Zn/Cr ( 18.2 % ) groups with no significant changes in the placebo group . The value for the TBARS of the control healthy Tunisian subjects was 2.08 ± 0.04 μmol/L and that of the Tunisian subjects with diabetes was 3.32 ± 0.05 μmol/L. This difference of 1.24 μmol/L between the control group and the subjects with diabetes was reduced from 36 % to 50 % in the three supplemented groups . Supplementation did not modify significantly HbA1C nor glucose homeostasis . No adverse effects  of Zn supplementation were observed on Cu status , HDL cholesterol nor interactions in Zn or Cr . Conclusions : These data suggest the potential beneficial antioxidant effects of the individual and combined supplementation of Zn and Cr in people with type 2 DM . These results are particularly important in light of the deleterious consequences of oxidative stress in people with diabetes BACKGROUND We investigated the potential effects of chromium supplementation on QTc interval duration in type 2 diabetic patients . METHODS Of 60 patients with type 2 diabetes mellitus , 30 were r and omly assigned to group A , and 30 to group B. Group A received 1000 microg of chromium picolinate ( CrPic ) daily for 3 months , followed by placebo in the next 3 months ; group B was treated with placebo for the first 3 months and CrPic in the next 3 months . At each visit , QT interval was measured on a  st and ard electrocardiogram  by averaging 3 consecutive beats in leads II and V4 and corrected for heart rate with Bazett formula . RESULTS Although baseline QTc interval was similar in both groups ( 422 + /- 34 milliseconds in group A vs 425 + /- 24 milliseconds in group B , P = .77 ) , QTc interval at 3 months was shorter in group A ( 406 + /- 35 milliseconds ) than in group B ( 431 + /- 26 milliseconds , P = .01 ) . In the following 3 months , QTc interval shortened in group B but not in group A , which result ed in a comparable QTc interval duration of both groups at the end of the study ( 414 + /- 28 milliseconds in group A vs 409 + /- 22 milliseconds in group B , P = .50 ) . Apart from body mass index ( 31.4 + /- 4.2 kg/m2 in patients with QTc shortening vs 28.7 + /- 4.2 kg/m2 in patients without QTc shortening , P = .03 ) , none of the clinical and laboratory variables predicted QTc interval shortening in our patient cohort . CONCLUSIONS Short-term chromium supplementation shortens QTc interval in patients with type 2 diabetes mellitus OBJECTIVE Phytoestrogen consumption has been shown to reduce risk factors for cardiovascular disease . Type 2 diabetes confers an adverse cardiovascular risk profile particularly in women after menopause . The aim of this study was to determine whether a dietary supplement with soy protein and isoflavones affected insulin resistance , glycemic control , and cardiovascular risk markers in postmenopausal women with type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 32 postmenopausal women with diet-controlled type 2 diabetes completed a r and omized , double blind , cross-over trial of dietary supplementation with phytoestrogens ( soy protein 30 g/day , isoflavones 132 mg/day ) versus placebo ( cellulose 30 g/day ) for 12 weeks , separated by a 2-week washout period . RESULTS Compliance with the dietary supplementation was > 90 % for both treatment phases . When compared with the mean percentage change from baseline seen after 12 weeks of placebo , phytoestrogen supplementation demonstrated significantly lower mean values for fasting insulin ( mean + /- SD 8.09 + /- 21.9 % , P = 0.006 ) , insulin resistance ( 6.47 + /- 27.7 % , P = 0.003 ) , HbA(1c ) ( 0.64 + /- 3.19 % , P = 0.048 ) , total cholesterol ( 4.07 + /- 8.13 % , P = 0.004 ) , LDL cholesterol ( 7.09 + /- 12.7 % , P = 0.001 ) , cholesterol/HDL cholesterol ratio ( 3.89 + /- 11.7 % , P = 0.015 ) , and free thyroxine ( 2.50 + /- 8.47 % , P = 0.004 ) . No significant change occurred in HDL cholesterol , triglycerides , weight , blood pressure , creatinine , dehydroepi and rosterone sulfate , and rostenedione , and the hypothalamic-pituitary-ovarian axis hormones . CONCLUSIONS These results show that dietary supplementation with soy phytoestrogens favorably alters insulin resistance , glycemic control , and serum lipoproteins in postmenopausal women with type 2 diabetes , thereby improving their cardiovascular risk profile Alpha-lipoic acid ( ALA ) , a naturally occuring compound and a radical scavenger was shown to enhance glucose transport and utilization in different experimental and animal models . Clinical studies described an increase of insulin sensitivity after acute and short-term ( 10 d ) parenteral administration of ALA . The effects of a 4-week oral treatment with alpha-lipoic acid were evaluated in a placebo-controlled , multicenter pilot study to determine see whether oral treatment also improves insulin sensitivity . Seventy-four patients with type-2 diabetes were r and omized to either placebo ( n = 19 ) ; or active treatment in various doses of 600 mg once daily ( n = 19 ) , twice daily ( 1200 mg ; n = 18 ) , or thrice daily ( 1800 mg ; n = 18 ) alpha-lipoic acid . An isoglycemic glucose-clamp was done on days 0 ( pre ) and 29 ( post ) . In this explorative study , analysis was done according to the number of subjects showing an improvement of insulin sensitivity after treatment . Furthermore , the effects of active vs. placebo treatment on insulin sensitivity was compared . All four groups were comparable and had a similar degree of hyperglycemia and insulin sensitivity at baseline . When compared to placebo , significantly more subjects had an increase in insulin-stimulated glucose disposal ( MCR ) after ALA treatment in each group . As there was no dose effect seen in the three different alpha-lipoic acid groups , all subjects receiving ALA were combined in the " active " group and then compared to placebo . This revealed significantly different changes in MCR after treatment ( + 27 % vs. placebo ; p < .01 ) . This placebo-controlled explorative study confirms previous observations of an increase of insulin sensitivity in type-2 diabetes after acute and chronic intravenous administration of ALA . The results suggest that oral administration of alpha-lipoic acid can improve insulin sensitivity in patients with type-2 diabetes . The encouraging findings of this pilot trial need to be substantiated by further investigations We demonstrated similar plasma concentrations and urinary losses but lower erythrocyte magnesium concentrations ( 2.18 + /- 0.04 vs 1.86 + /- 0.03 mmol/L , P less than 0.01 ) in twelve aged ( 77.8 + /- 2.1 y ) vs 25 young ( 36.1 + /- 0.4 y ) , nonobese subjects . Subsequently , aged subjects were enrolled in a double-blind , r and omized , crossover study in which placebo ( for 4 wk ) and chronic magnesium administration ( CMA ) ( 4.5 g/d for 4 wk ) were provided . At the end of each treatment period an intravenous glucose tolerance test ( 0.33 g/kg body wt ) and a euglycemic glucose clamp with simultaneous [D-3H]glucose infusion and indirect calorimetry were performed . CMA vs placebo significantly increased erythrocyte magnesium concentration and improved insulin response and action . Net increase in erythrocyte magnesium significantly and positively correlated with the decrease in erythrocyte membrane microviscosity and with the net increase in both insulin secretion and action . In aged patients , correction of a low erythrocyte magnesium concentration may allow an improvement of glucose h and ling BACKGROUND Some studies have shown potential benefit of vitamin E on platelet function , but several clinical trials failed to show improved cardiovascular outcome with alpha-tocopherol supplementation . Gamma-tocopherol , a major dietary form of vitamin E , may have protective properties different from those of alpha-tocopherol . OBJECTIVE We compared the effects of supplementation with alpha-tocopherol ( 500 mg ) and a gamma-tocopherol-rich compound ( 500 mg , containing 60 % gamma-tocopherol ) on serum and cellular tocopherol concentrations , urinary tocopherol metabolite excretion , and in vivo platelet activation in subjects with type 2 diabetes . DESIGN Fifty-eight subjects were r and omly assigned to receive either 500 mg alpha-tocopherol/d , 500 mg mixed tocopherols/d , or matching placebo .  Serum , erythrocyte , and platelet tocopherol and urinary metabolite concentrations were measured at baseline and after the 6-wk intervention . Soluble CD40 lig and , urinary 11-dehydro-thromboxane B2 , serum thromboxane B2 , soluble P-selectin , and von Willebr and factor were measured as biomarkers of in vivo platelet activation . RESULTS Serum alpha-tocopherol increased with both tocopherol treatments . Serum and cellular gamma-tocopherol increased 4-fold ( P < 0.001 ) in the mixed tocopherol group , whereas red blood cell gamma-tocopherol decreased significantly after alpha-tocopherol supplementation . Excretion of alpha-carboxyethyl-hydroxychroman increased significantly after supplementation with alpha-tocopherol and mixed tocopherols . Excretion of gamma-carboxyethyl-hydroxychroman increased significantly after supplementation with mixed tocopherols and after that with alpha-tocopherol , which may reflect the displacement of gamma-tocopherol by alpha-tocopherol due to incorporation of the latter into lipoproteins in the liver . Neither treatment had any significant effect on markers of platelet activation . CONCLUSIONS Supplementation with alpha-tocopherol decreased red blood cell gamma-tocopherol , whereas mixed tocopherols increased both serum alpha-tocopherol and serum and cellular gamma-tocopherol . Changes in serum tocopherol closely reflect changes in cellular concentrations of tocopherols after supplementation Ten control ( healthy ) subjects and 15 non-insulin-dependent diabetics underwent an oral glucose-tolerance test and a euglycemic hyperinsulinemic glucose clamp before and after vitamin E supplementation ( 900 mg/d for 4 mo ) . In control subjects ( placebo-treated vs vitamin E-supplemented subjects , respectively ) vitamin E reduced the area under the curve for glucose ( 344 + /- 21 vs 287 + /- 13 mmol . L-1 x min-1 ; P < 0.05 ) and increased total body glucose disposal ( 39.0 + /- 0.3 vs 47.6 + /- 0.4 mumol.kg lean body mass-1 x min-1 ; P < 0.05 ) and non-oxidative glucose metabolism ( 23.4 + /- 0.2 vs 30.8 + /- 0.3 mumol.kg lean body mass-1 x min-1 ; P < 0.05 ) . In diabetics ( placebo-treated vs vitamin E-supplemented subjects , respectively ) vitamin E supplementation reduced glucose area under the curve ( 614 + /- 129 vs 544 + /- 98 mmol . L-1 x min-1 ; P < 0.03 ) and increased glucose disappearance ( 19.4 + /- 0.4 vs 26.4 + /- 0.7 mumol.kg lean body mass-1.min-1 ; P < 0.03 ) , total glucose disposal ( 19.0 + /- 0.7 vs 28.1 + /- 0.4 mumol.kg lean body mass-1 x min-1 ; P < 0.02 ) , and nonoxidative glucose metabolism ( 8.5 + /- 0.3 vs 13.9 + /- 0.3 mumol.kg lean body mass-1 x min-1 ; P < 0.02 ) . Therefore we conclude that administration of pharmacologic doses of vitamin E is a useful tool to reduce oxidative stress and improve insulin action OBJECTIVE To study the effects of supplementation with organic and inorganic chromium on glucose tolerance , serum lipids , and drug dosage in type 2 diabetes patients , in the hope of finding a better and more economical method of control . METHODS Seventy eight type 2 diabetes patients were divided r and omly into two groups and given Brewer 's yeast ( 23.3ug Cr/day ) , and CrCl3 ( 200ug Cr/day ) sequentially with placebo in between , in a double blind cross-over design of four stages , each lasting 8 weeks . At the beginning and end of each stage , subjects were weighed , their dietary data and drug dosage recorded , and blood and urine sample s were collected for analysis of glucose ( fasting and 2 hour post 75 g glucose load ) fructosamine , triglycerides , total and HDL-cholesterol , and serum and urinary chromium . RESULTS Both supplements caused a significant decrease in the means of glucose ( fasting and 2 hour post glucose load ) , fructosamine and triglycerides . The means of HDL-cholesterol , and serum and urinary chromium were all increased . The mean drug dosage decreased slightly ( and significantly in case of Glibenclamide ) after both supplements and some patients no longer required insulin . No change was noted in dietary intakes or Body Mass Index . A higher percentage of subjects responded positively to Brewer 's yeast chromium , which was retained more by the body , with effects on fructosamine , triglycerides , and HDL-cholesterol maintained in some subjects when placebo followed it , and mean urinary chromium remaining significantly higher than zero time mean . CONCLUSION Chromium supplementation gives better control of glucose and lipid variables while decreasing drug dosage in type 2 diabetes patients . A larger scale study is needed to help decide on the convenient chemical form , and dosage required to achieve optimal response Abstract Through the use of a double-blind cross-over investigative method , the effect of trivalent chromium supplements on blood sugar concentrations of normal and diabetic human subjects was evaluated . Four normal and 10 diabetic subjects took 50 μg . of trivalent chromium and a chromium-placebo thrice daily by mouth for 16-week periods . Chromium did not improve hyperglycemia in diabetic patients , and there was no difference in diabetic glucose tolerance measured after placebo and chromium treatment . Normal glucose tolerance was also unaffected . Despite evidence that trivalent chromium may be an essential micronutrient for maintenance of normal glucose tolerance in rats , results of this investigation do not support suggestions of a similar role in man The aim of this study was to determine the effect of chromium (Cr)-enriched yeast on blood glucose and insulin variables , blood lipids , and blood markers of oxidative stress in persons with type 2 diabetes mellitus ( median duration : 3.0 yr ) . Thirty-six subjects ( 9 men , 27 women ; mean age : 61.3 yr ; mean body mass index : 34.33 kg/m2 ) were supplemented with 400 μg Cr/d as Cr-enriched yeast ( n=19 ) or placebo ( n=17 ) for 12 wk in a r and omized , double-blind study . The most interesting results were obtained by comparison of the change in the placebo group to the change in the Cr group . The Cr group showed a significantly greater increase in serum Cr compared to the placebo group ( p<0.05 ) . Supplementation with Cr-enriched yeast was associated with a significant decrease in fasting serum glucose compared to placebo ( p<0.01 ) . Blood markers of oxidative stress glutathione peroxidase activity and levels of reduced glutathione were essentially unchanged in the Cr group after 12 wk , but decreased significantly in the placebo group ( p<0.05 , p<0.01 , respectively ) , Serum HbA1c and glycated protein ( fructosamine ) were essentially unchanged in the Cr group , whereas HbA1c tended to increase in the placebo group ( from 6.94 % to 7.11 % ) . Fasting serum insulin decreased in both groups , with a greater tendency in the Cr group ( −16.5 % vs −9.5 % ) . These data suggest that supplementation of well-controlled type 2 diabetics with Cr-enriched yeast is safe and can result in improvements in blood glucose variables and oxidative stress Abstract —Experimental evidence suggests that acute parenteral administration of high-dose ascorbic acid has beneficial vascular effects in type 2 diabetes . We studied the hemodynamic effects of chronic oral supplementation in this condition . Thirty patients , 45 to 70 years of age , with type 2 diabetes , were r and omly assigned in a double-blind manner to receive 500 mg ascorbic acid daily by mouth or placebo . Patients were studied at baseline and after 4 weeks of assigned treatment . The central aortic augmentation index ( AgIx ) and the time to wave reflection ( Tr ) were derived from radial artery pulse wave analysis data . AgIx and Tr were used as measures of systemic arterial stiffness and aortic stiffness , respectively . Ascorbic acid  decreased brachial systolic blood pressure from 142.1±12.6 ( SD ) to 132.3±12.1 mm Hg ( difference [ 95 % CI ] 9.9 [ 4.7 , 15.0];P < 0.01 ) , brachial diastolic pressure from 83.9±4.8 to 79.5±6.0 mm Hg ( 4.4 [ 1.8 , 7.0];P < 0.01 ) , and AgIx from 26.8±5.5 % to 22.5±6.8 % ( 4.3 [ 1.5 , 7.1];P < 0.01 ) . Tr increased from 137.1±12.6 to 143.4±9.2 ms ( −6.3 [ −10.1 , −2.5];P < 0.01 ) . Placebo had no hemodynamic effects , and this difference between treatments was significant ( P < 0.01 for blood pressure and Tr , P = 0.03 for AgIx ) . We have therefore shown that after 1 month , oral ascorbic acid  lowered arterial blood pressure and improved arterial stiffness in patients with type 2 diabetes . As strict control of blood pressure reduces cardiovascular risk in diabetes , ascorbic acid supplementation may potentially be a useful and inexpensive adjunctive therapy . Larger and longer studies now need to be performed This triple-blind , placebo-controlled clinical trial was conducted to determine the effect of the vitamin E on fasting blood sugar ( FBS ) , serum insulin , and glycated hemoglobin ( GHb ) in type 11 diabetic patients ( NIDDM ) . A total of 100 patients , with no complications , aged 20 - 60 years old were chosen from those consulting the Isfahan Social Security Service Diabetes Clinic and divided r and omly into two treated and placebo groups , and matched for age , sex , level of education , and occupation . The treated and placebo groups were given vitamin E tablets ( 200 IU/day ) and placebo respectively .  Serum vitamin E , total cholesterol ( TC ) , triglycerides ( TG ) , FBS , insulin , and GHb were measured at the beginning and at the end of the study ( a period of 27 weeks ) ; FBS , GHb and insulin levels were also determined several times during the period . Blood lipids and FBS were measured using the ELAN 2000 autoanalyzer at the Isfahan Cardiovascular Research Center , while for measuring insulin the enzyme-linked immunosorbent assay ( ELISA ) method was used ; GHb was determined calorimetrically ( thiobarbituric acid ) , and for vitamin E measurements the Hansen and Warwick method was used , by which the vitamin E was determined fluorometrically . The findings of this study show no effect of  vitamin E supplementation in the patients : GHb did not change appreciably , FBS was reduced nonsignificantly ( -4.3 % in the treated group vs. -14.0 % in the placebo group , p < 0.05 ) . In the case of insulin , no increase was seen ; instead , a decrease was observed ( slightly more than 17 % in the two groups , p = 0.15 ) . No changes were observed in the levels of blood lipids . It was concluded that a daily vitamin E supplement of 200 IU for a period of 27 weeks does not affect insulin , GHb , or FBS in type II diabetic patients . However , since this antioxidant vitamin is beneficial in other ways in these patients , it would seem justified to recommend its use . Certainly , more extensive research is necessary to draw definite conclusions Atherosclerosis is associated with stiffening of conduit arteries and increased platelet activation , partly as a result of reduced bioavailability of nitric oxide ( NO ) , a mediator that normally has a variety of protective effects on blood vessels and platelets . Increased levels of oxygen free radicals are a feature of atherosclerosis that contributes to reduced NO bioavailability and might lead to increased arterial stiffness and platelet activation .  Vitamin C is a dietary antioxidant that inactivates oxygen free radicals . This placebo-controlled , double-blind , r and omized study was design ed to establish whether acute oral administration of vitamin C ( 2 g ) , would reduce arterial stiffness and in vitro platelet aggregation in healthy male volunteers .  Plasma vitamin C concentrations increased from 42+/-8 to 104+/-8 microM at 6 h after oral administration , and were associated with a significant reduction in augmentation index , a measure of arterial stiffness ( by 9.6+/-3.0 % ; p = 0.016 ) , and ADP-induced platelet aggregation ( by 35+/-13 % ; p = 0.046 ) . There was no change in these parameters after placebo . Vitamin C , therefore , appears to have beneficial effects , even in healthy subjects . The mechanism responsible is likely to involve protection of NO from inactivation by oxygen free radicals , but this requires confirmation . If similar effects are observed in patients with atherosclerosis or risk factors , vitamin C supplementation might prove an effective therapy in cardiovascular disease 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 Chromium is an essential nutrient involved in normal carbohydrate and lipid metabolism . The chromium requirement is postulated to increase with increased glucose intolerance and diabetes . The objective of this study was to test the hypothesis that the elevated intake of supplemental chromium is involved in the control of type 2 diabetes . Individuals being treated for type 2 diabetes ( 180 men and women ) were divided r and omly into three groups and supplemented with : 1 ) placebo , 2 ) 1.92 μmol ( 100 μg ) Cr as chromium picolinate two times per day , or 3 ) 9.6 μmol ( 500 μg ) Cr two times per day . Subjects continued to take their normal medications and were instructed not to change their normal eating and living habits . HbA1c values improved significantly after 2 months in the group receiving 19.2 pmol ( 1,000 pg ) Cr per day and was lower in both chromium groups after 4 months ( placebo , 8.5 ± 0.2 % ; 3.85 pmol Cr , 7.5 ± 0.2 % ; 19.2 pmol Cr , 6.6 ± 0.1 % ) . Fasting glucose was lower in the 19.2-μmol group after 2 and 4 months ( 4-month values : placebo , 8.8 ± 0.3 mmol/1 ; 19.2 μmol Cr , 7.1 ± 0.2 mmol/1 ) . Two-hour glucose values were also significantly lower for the subjects consuming 19.2 μmol supplemental Cr after both 2 and 4 months ( 4-month values : placebo , 12.3 ± 0.4 mmol/1 ; 19.2 μmol Cr , 10.5 ± 0.2 mmol/1 ) . Fasting and 2-h insulin values decreased significantly in both groups receiving supplemental chromium after 2 and 4 months . Plasma total cholesterol also decreased after 4 months in the subjects receiving 19.2 μmol/day Cr . These data demonstrate that supplemental chromium had significant beneficial effects on HbA1c , glucose , insulin , and cholesterol variables in subjects with type 2 diabetes . The beneficial effects of chromium in individuals with diabetes were observed at levels higher than the upper limit of the Estimated Safe and Adequate Daily Dietary Intake 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 BACKGROUND Endothelial dysfunction and arterial stiffening are commonly observed in type 2 diabetes . These abnormalities might be secondary to increased plasma concentrations of homocysteine . We sought to determine whether oral folic acid supplementation , by lowering homocysteine levels , enhanced endothelial function and reduced arterial stiffness in type 2 diabetes . METHODS Twenty-six type 2 diabetic patients ( age 56.5 + /- 0.9 years , diabetes duration 5.5 + /- 0.6 years , means + /- SEM ) with no history of cardiovascular disease received 5 mg/d of oral folic acid or placebo for 4 weeks in a double-blind , r and omized controlled , parallel group trial . The following parameters were measured before and after treatment : 1 ) endothelial function ( forearm arterial blood flow during local intra-arterial administration of endothelium-dependent [ acetylcholine 1.5 , 4.5 , and 15 microg/min ] and endothelium-independent [ sodium nitroprusside 1 , 2 , and 4 microg/min ] vasodilators ) ; and 2 ) carotid-radial and carotid-femoral pulse wave velocity . RESULTS Folic acid reduced plasma homocysteine concentrations and enhanced endothelium-dependent vasodilatation during each acetylcholine infusion rate ( mean and 95 % confidence interval post versus pretreatment differences in forearm arterial blood flow ratio between the infused and control arm + 0.19 ( 0.03 - 0.35 ) , P < .01 ; + 0.39 ( 0.02 - 0.81 ) , P < .05 ; and + 0.40 ( 0.09 - 0.89 ) , P < .05 , respectively ) . Endothelium-independent vasodilatation and pulse wave velocity were not affected . No significant changes in forearm arterial blood flow and pulse wave velocity were observed in the placebo group . Multiple regression analysis showed that changes in folic acid , but not homocysteine , concentrations independently described changes in maximal endothelium-dependent vasodilatation . CONCLUSIONS Short-term oral folic acid supplementation significantly enhances endothelial function in type 2 diabetic patients , independent of homocysteine lowering OBJECTIVE Chromium treatment has been reported to improve glycemic control and insulin sensitivity in specific population s of patients with type 2 diabetes . The aim of this study was to determine the effect of chromium treatment on glycemic control in a Western population of insulin-dependent patients with type 2 diabetes . RESEARCH DESIGN AND METHODS In this 6-month double-blind study , patients with an HbA(1c ) ( A1C ) > 8 % and insulin requirements of > 50 units/day were r and omly assigned to receive treatment with placebo or 500 or 1,000 mug chromium daily in the form of chromium picolinate . The primary efficacy parameter was a change in A1C . Secondary end points were changes in lipid profile , BMI , blood pressure , and insulin requirements . RESULTS In this per- protocol analysis ( n = 46 ) , the decrease in A1C was approximately equal across the three groups ( 0.4 % ) . All patients had a BMI > 25 kg/m(2 ) . No differences were found in the secondary end points . We found a weak relationship between an increasing serum chromium concentration and improvement of the lipid profile . CONCLUSIONS There is no evidence that high-dose chromium treatment is effective in obese Western patients with type 2 diabetes OBJECTIVE The role of selenium in preventing cardiovascular diseases has been largely described . Oxidative stress and the subsequent activation of nuclear factor-kappa B ( NF-kappaB ) have been linked to the development of vascular complications . We investigated the effects of selenium supplementation in type 2 diabetic patients on several oxidative stress parameters and NF-kappaB activity . METHODS We enrolled 56 type 2 diabetic patients with similar glycaemic control : 21 were supplemented by selenium ( 960 micro g d(-1 ) , 3 months ) and 27 received a placebo  , and 10 nondiabetic subjects formed the control group . To determine NF-kappaB activation , we used an electrophoretic mobility shift assay followed by a semi-quantitative determination of NF-kappaB in peripheral blood mononuclear cells . RESULTS Selenium treatment result ed in a significant increase in plasma selenium and red-cell Se GSH px activity . It had no effect on lipid peroxidation measured by malone-dialdehyde ( MDA ) or on red-cell Cu/Zn SOD . NF-kappaB activity was increased by 80 % in diabetic patients . In patients receiving selenium supplementation , selenium NF-kappaB activity was significantly reduced , reaching the same level as the nondiabetic control group . CONCLUSION In type 2 diabetic patients , activation of NF-kappaB measured in peripheral blood monocytes can be reduced by selenium supplementation , confirming its importance in the prevention of cardiovascular diseases 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 Renal accumulation of advanced glycation end products ( AGEs ) has been linked to the progression of diabetic nephropathy . Cleavage of pre-formed AGEs within the kidney by a cross-link breaker , such as ALT-711 , may confer renoprotection in diabetes . STZ diabetic rats were r and omized into a ) no treatment ( D ) ; b ) treatment with the AGE cross-link breaker , ALT-711 , weeks 16 - 32 ( DALT early ) ; and c ) ALT-711 , weeks 24 - 32 ( DALT late ) . Treatment with ALT-711 result ed in a significant reduction in diabetes-induced serum and renal AGE peptide fluorescence , associated with decreases in renal carboxymethyllysine and RAGE immunostaining . Cross-linking of tail tendon collagen seen in diabetic groups was attenuated only by 16 weeks of ALT-711 treatment . ALT-711 , independent of treatment duration , retarded albumin excretion rate ( AER ) , reduced blood pressure , and renal hypertrophy . It also reduced diabetes-induced increases in gene expression of transforming growth factor beta1 ( TGF-beta1 ) , connective tissue growth factor ( CTGF ) , and collagen IV . However , glomerulosclerotic index , tubulointerstitial area , total renal collagen , nitrotyrosine , protein expression of collagen IV , and TGF-beta1 only showed improvement with early ALT treatment alone . This study demonstrates the utility of a cross-link breaker as a treatment for diabetic nephropathy and describes effects not only on renal AGEs but on putative mediators of renal injury , such as prosclerotic cytokines and oxidative stress Epidemiologic studies have correlated fasting and postload insulin levels with the risk of coronary heart disease , assuming that insulin levels are reliable markers of insulin resistance . However , this assumption has not been systematic ally studied . The author measured insulin response to an oral glucose load and quantitated insulin resistance using the euglycemic hyperinsulinemic clamp technique to evaluate the correlation between insulin level and the degree of insulin resistance in individuals with varying degrees of glucose tolerance . Subjects were r and omly selected from previous population studies done in 1987 - 1989 at the Department of Medicine of the University of Kuopio in east Finl and . Altogether , 50 subjects with normal glucose tolerance , 28 with impaired glucose tolerance , and 54 with non-insulin-dependent diabetes mellitus were studied . Correlations of insulin resistance ( whole-body glucose uptake in clamp studies ) with fasting or postload insulin levels were remarkably consistent , ranging from -0.58 to -0.74 ( p < 0.01 ) in subjects with normoglycemia . In contrast , corresponding correlations were substantially weaker in subjects with impaired glucose tolerance and non-insulin-dependent diabetes . Among these subjects , only the fasting insulin level correlated significantly with insulin resistance ( -0.47 , p < 0.05 and -0.48 , p < 0.01 , respectively ) . The authors conclude that in population studies , only the fasting insulin level should be used as a marker of insulin resistance , particularly in subjects with abnormal glucose tolerance Type II diabetes is characterized by increased oxidative stress , endothelial dysfunction and hypertension . We investigated whether short-term treatment with oral vitamin C reduces oxidative stress and improves endothelial function and blood pressure in subjects with Type II diabetes . Subjects ( n = 35 ) received vitamin C ( 1.5 g daily in three doses ) or matching placebo for 3 weeks in a r and omized , double-blind , parallel-group design . Plasma concentrations of 8-epi-prostagl and in F(2alpha ) ( 8-epi-PGF(2alpha ) ) , a non-enzymically derived oxidation product of arachidonic acid , were used as a marker of oxidative stress . Endothelial function was assessed by measuring forearm blood flow responses to brachial artery infusion of the endothelium-dependent vasodilator acetylcholine ( with nitroprusside as an endothelium-independent control ) and by the pulse wave responses to systemic albuterol ( endothelium-dependent vasodilator ) and glyceryl trinitrate ( endothelium-independent vasodilator ) . Plasma concentrations of vitamin C  increased from 58+/-6 to 122+/-10 micromol/l after vitamin C , but 8-epi-PGF(2alpha ) levels ( baseline , 95+/-4 pg/l ; after treatment , 99+/-5 pg/l ) , blood pressure ( baseline , 141+/-5/80+/-2 mmHg ; after treatment , 141+/-5/81+/-3 mmHg ) and endothelial function , as assessed by the systemic vasodilator response to albuterol and by the forearm blood flow response to acetylcholine , were not significantly different from baseline or placebo . Thus treatment with vitamin C ( 1.5 g daily ) for 3 weeks does not significantly improve oxidative stress , blood pressure or endothelial function in patients with Type II diabetes A double-blind , placebo-controlled , r and omized , multi-center study was performed with 77 diabetes type II patients to investigate anti-diabetic effects of the French maritime pine bark extract , Pynogenol . Supplementation with 100 mg Pycnogenol for 12 weeks , during which a st and ard anti-diabetic treatment was continued , significantly lowered plasma glucose levels as compared to placebo .  HbA1(c ) was also lowered ; however , the difference as compared to placebo was statistically significant only for the first month . In the Pycnogenol-group  endothelin-1 was significantly decreased , while 6-ketoprostagl and in F(1a ) in plasma was elevated compared to placebo . Nitric oxide levels in plasma increased during treatment in both groups , but , differences did not reach statistical significance . Pycnogenol was well-tolerated with ECG , electrolytes , creatinine and blood urea nitrogen remaining unchanged in both groups . Mild and transient unwanted effects were reported for both groups without significant differences . Supplementation of Pycnogenol to conventional diabetes treatment lowers glucose levels and improves endothelial function Objective Oxidative stress has been suggested to play a role in the development of diabetes , hypertension and vascular dysfunction . Vitamin E , a major lipid-soluble dietary antioxidant , has two major dietary forms , α-tocopherol and γ-tocopherol . The potential importance of γ-tocopherol has largely been overlooked . Our aim was to investigate the effect of α-tocopherol and γ-tocopherol supplementation on 24-h ambulatory blood pressure ( BP ) and heart rate , vascular function and oxidative stress in individuals with type 2 diabetes . Method Fifty-eight individuals with type 2 diabetes were r and omized in a double-blind , placebo-controlled trial . Participants were r and omized to a daily dose of 500 mg/day RRR-α-tocopherol , 500 mg/day mixed tocopherols ( 60 % γ-tocopherol ) or placebo for 6 weeks . Primary endpoints were 24-h ambulatory BP and heart rate , endothelium-dependent and independent vasodilation and plasma and urinary F2-isoprostanes . Results Treatment with α-tocopherol significantly increased systolic BP [ 7.0 ( 5.2 , 8.8 ) mmHg , P < 0.0001 ] , diastolic BP [ 5.3 ( 4.0 , 6.5 ) mmHg , P < 0.0001 ] , pulse pressure [ 1.8 ( 0.6 , 3.0 ) mmHg , P < 0.005 ] and heart rate [ 2.0 ( 0.6 , 3.3 ) bpm , P < 0.005 ] versus placebo . Treatment with mixed tocopherols  significantly increased systolic BP [ 6.8 ( 4.9 , 8.6 ) mmHg , P < 0.0001 ] , diastolic BP [ 3.6 ( 2.3 , 4.9 ) mmHg , P < 0.0001 ] , pulse pressure [ 3.2 ( 2.0 , 4.4 ) mmHg , P < 0.0001 ] and heart rate [ 1.8 ( 0.5 , 3.2 ) bpm , P < 0.01 ] versus placebo . Treatment with α-tocopherol or mixed tocopherols  significantly reduced plasma F2-isoprostanes versus placebo , but had no effect on urinary F2-isoprostanes . Endothelium-dependent and independent vasodilation was not affected by either treatment . Conclusion In contrast to our initial hypothesis , treatment with either α- or mixed tocopherols  significantly increased BP , pulse pressure and heart rate in individuals with type 2 diabetes OBJECTIVE To investigate the effect of chromium picolinate supplementation on the lipid profile of the predominantly Hispanic population of non-insulin-dependent diabetes mellitus ( NIDDM ) patients in San Antonio , Texas . RESEARCH DESIGN AND METHODS A prospect i ve , double-blind , placebo-controlled , crossover study was performed on 14 men and 16 women . Initially , each patient was r and omly assigned to receive either chromium picolinate or placebo for 2 months . This initial treatment phase was followed by a 2-month washout period . Subjects were then crossed-over and received the alternate capsule for an additional 2 months . Fasting blood glucose , HbA1c , and serum lipids were compared at the end of each treatment phase . RESULTS Twenty-eight of the originally enrolled 30 patients completed the study . There were no adverse reactions to chromium reported . There were no differences noted between the control and chromium-treated subjects in glucose control , high-density lipoprotein cholesterol levels , or low-density lipoprotein cholesterol levels . Triglyceride ( TG ) levels were reduced significantly ( 17.4 % ; P < 0.05 ) during the 2 months of chromium supplementation . CONCLUSIONS Ours is the first report of a significant reduction in serum TGs in a group of NIDDM patients treated with chromium . The low cost and excellent safety profile of chromium make it an attractive lipid-lowering agent for this population . Long-term studies are needed to determine if the short-term changes in plasma lipids can be sustained Tocopherol has been shown to have antiplatelet effects in insulin-dependent diabetes mellitus . However , its antiplatelet effect in non-insulin-dependent diabetes mellitus ( NIDDM ) remains to be established . In this report , the antiplatelet effect of tocopherol was assessed in a r and omized , double-blind and crossover study of 15 NIDDM subjects . Each subject received tocopherol ( dl-alpha-tocopherol nicotinate , 200 mg , tid ) and a placebo for two six-week treatment periods separated by a three-week period in between for wash-out . The mechanisms of the antiplatelet effect of tocopherol were also studied in vitro . A significant decrease in platelet reactivity was observed after tocopherol treatment as compared with the pretest , and the magnitude of the decrease during tocopherol treatment was significantly evident when compared with that of the placebo treatment , as assessed by collagen ( 5 , 10 micrograms/mL)-induced platelet aggregation of whole blood . A dose-dependent reduction in both ADP- and collagen-induced platelet aggregation was observed with tocopherol from 0.1 to 3.0 mM in vitro . No corresponding changes in ATP secretion and thromboxane synthesis were observed . Tocopherol also significantly inhibited fibrinogen-induced aggregation of elastase-treated platelets at a concentration of 0.1 mM. We demonstrated that platelet aggregation of whole blood ex vivo , among 15 NIDDM subjects was suppressed in tocopherol treatment , so tocopherol may have an antiplatelet effect in NIDDM subjects . The inhibitory effect of the platelet aggregation of tocopherol may be partially accomplished through interference with fibrinogen binding towards its receptor OBJECTIVE To evaluate the effect of vitamin E supplementation on the susceptibility of low-density lipoprotein ( LDL ) and LDL subfractions to oxidation and on protein glycation in non-insulin-dependent diabetes mellitus ( NIDDM ) . RESEARCH DESIGN AND METHODS Twenty-one men with NIDDM ( HbA1c = 6 - 10 % ) , ages 50–70 , were r and omly assigned to either 1,600 IU/day of vitamin E or placebo for 10 weeks after a 4-week placebo period . LDL and LDL subfractions were isolated after 4 weeks of placebo and after 6 and 10 weeks of therapy . Susceptibility of LDL to copper-mediated oxidation was measured by conjugated diene formation ( lag time ) and formation of thiobarbituric acid-reactive substances ( TBARS ) . Fasting serum glucose , mean weekly blood glucose , HbA1c , and glycated plasma protein concentrations were also determined at these time points . RESULTS Vitamin E content in plasma and LDL increased 4.0- and 3.7-fold , respectively , in the vitamin E-treated group . Vitamin E decreased the susceptibility of LDL to oxidation in comparison with placebo ( lag time , 243 ± 46 vs. 151 ± 22 min , P < 0.01 ; 3 h TBARS , 24 ± 12 vs. 66 ± 18 nmol malondialdehyde/mg LDL , P < 0.05 ) . Vitamin E content also increased significantly in both buoyant and dense LDL subfractions , and their oxidation was dramatically reduced . The lag time of LDL oxidation correlated well with the content of vitamin E in both LDL and its subfractions ( r = 0.69–0.92 ) . Glycemic indexes did not change significantly in either group during the study . Protein glycation , including glycated hemoglobin , glycated albumin , glycated total plasma proteins , and glycated LDL were unchanged in the vitamin E group . CONCLUSIONS Supplementation of vitamin E in NIDDM leads to enrichment of LDL and LDL subfractions and reduced susceptibility to oxidation . Despite a greater percentage increase in vitamin E content in small dense LDL , it remained substantially more susceptible to oxidation than was buoyant LDL . This suggests that dense , LDL may gain less protection against oxidation from antioxidant supplementation than does larger , more buoyant LDL . In contrast to previous reports , vitamin E supplementation did not reduce glycation of intracellular or plasma proteins OBJECTIVE Diabetic hyperglycemia promotes sorbitol production from glucose via aldose reductase . Since the intracellular accumulation of sorbitol , or its sequelae , are postulated to contribute to the progression of chronic diabetic complications , aldose reductase inhibitors ( ARI ) offer therapeutic promise . Others have shown that vitamin C at pharmacologic doses decreases erythrocyte ( RBC ) sorbitol . We examined whether smaller , physiologic doses of vitamin C were also effective in individuals with insulin-dependent diabetes mellitus ( IDDM ) and whether vitamin C was an ARI in vitro . METHODS Vitamin C supplements ( 100 or 600 mg ) were taken daily for 58 days by young adults with IDDM and nondiabetic adults in an otherwise free-living design . Diabetic control was monitored by fasting plasma glucose , glycosylated hemoglobin , and glycosuria and was moderate to poor throughout the study . RBC sorbitol was measured at baseline and again at 30 and 58 days . Three-day dietary records and 24-hour urine collection s were performed for each sampling day . RESULTS RBC sorbitol levels were significantly elevated in IDDMs , on average doubled , despite their more than adequate dietary intakes of vitamin C and normal plasma concentrations . Vitamin C supplementation at either dose normalized the RBC sorbitol in IDDMs within 30 days . This correction of sorbitol accumulation was independent of changes in diabetic control . Furthermore , our in vitro studies show that ascorbic acid inhibited aldose reductase activity . CONCLUSIONS Vitamin C supplementation is effective in reducing sorbitol accumulation in the erythrocytes of diabetics . Given its tissue distribution and low toxicity , we suggest a superiority for vitamin C over pharmaceutic ARIs In order to confirm the effect of ascorbic acid ( AA ) on human erythrocyte sorbitol accumulation  and explore its mechanism of action , the effects of ascorbic acid in vitro on the sorbitol ( S ) and glucose ( EG ) content of human erythrocytes and in particular on the S/EG ratio as a marker of aldose reductase ( AR ) activity were carefully observed . The results showed that both the accumulation of erythrocyte sorbitol and the S/EG ratio were strongly reduced by the addition of AA . The sorbitol content in the erythrocyte and the S/EG ratio were reduced by a maximum of 87.3 % and 83.4 % and 93.8 % and 63.9 % when the medium 's AA concentration was at its peak with 5.6 mmol/l and 28 mmol/l glucose in the medium , respectively . The contents of erythrocyte glucose measured coincidentally revealed a positive correlation with the ascorbic acid concentration in the medium during incubation in 5.6 mmol/l glucose while at a higher glucose level ( 28 mmol/l ) in the medium the correlation became negative . These results suggested that the polyol pathway could be inhibited effectively by AA through its direct action on AR . The results of a double-blind cross-over trial using AA tablets or inositol tablets in eight diabetic patients showed that the supplementation of 1000 mg AA/day for 2 weeks result ed in reductions of 12.2 % and 21.8 % in erythrocyte sorbitol and red cell sorbitol/plasma glucose ( S/PG ) ratio , respectively ( P < 0.05 ) , whereas the fasting plasma glucose levels measured coincidentally revealed no changes ( P > 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Vitamin E isomers may protect against atherosclerosis . The aim of this study was to compare the effects of supplementation with either alpha-tocopherol ( alphaT ) or mixed tocopherols rich in gamma-tocopherol ( gammaT ) on markers of oxidative stress and inflammation in patients with type 2 diabetes . METHODS In a double-blind , placebo-controlled trial , 55 patients with type 2 diabetes were r and omly assigned to receive ( 500 mg/day ) ( a ) alphaT , ( b ) mixed tocopherols , or ( c ) placebo for 6 weeks . Cellular tocopherols , plasma and urine F(2)-isoprostanes , erythrocyte antioxidant enzyme activities , plasma inflammatory markers , and ex vivo assessment of eicosanoid synthesis were analyzed pre- and postsupplementation . RESULTS Neutrophil alphaT and gammaT increased ( both P < 0.001 ) with mixed tocopherol supplementation , whereas alphaT ( P < 0.001 ) increased and gammaT decreased ( P < 0.005 ) after alphaT supplementation . Both alphaT and mixed tocopherol supplementation result ed in reduced plasma F(2)-isoprostanes ( P < 0.001 and P = 0.001 , respectively ) but did not affect 24-h urinary F(2)-isoprostanes or erythrocyte antioxidant enzyme activities . Neither alphaT nor mixed tocopherol supplementation affected plasma C-reactive protein , interleukin 6 , tumor necrosis factor-alpha , or monocyte chemoattractant protein-1 . Stimulated neutrophil leukotriene B(4 ) production decreased significantly in the mixed tocopherol group ( P = 0.02 ) but not in the alphaT group ( P = 0.15 ) . CONCLUSIONS The ability of tocopherols to reduce systemic oxidative stress suggests potential benefits of vitamin E supplementation in patients with type 2 diabetes . In population s with well-controlled type 2 diabetes , supplementation with either alphaT or mixed tocopherols rich in gammaT is unlikely to confer further benefits in reducing inflammation The aim of this study is to evaluate the effect and safety of chromium-containing milk powder in patients with type 2 diabetes mellitus . A r and omized , double-blind , placebo-controlled trial was conducted in Taiwan . A total of 60 patients with type 2 diabetes mellitus , aged 30 to 75 years , and on a dose of gliclazide sulfonylurea agent ( < or = 160 mg/d ) for at least 3 months were enrolled . Their glycosylated hemoglobin ranged from 7.5 % to 12 % , fasting plasma glucose ( FPG ) from 140 to 250 mg/dL , and body mass index from 20 to 35 kg/m(2 ) . The subjects were divided into 2 groups , one group to receive chromium-containing milk powder ( chromium 200 microg/20 g milk powder ) and the other to receive placebo twice a day for 16 weeks . Frequently sample d intravenous glucose tolerance test ( IVGTT ) was performed before and after treatment . The chromium group demonstrated a lower FPG and fasting insulin ( -38.1 + /- 9.2 vs 63 + /- 8 . 5 mg/dL and -1.7 + /- 0.2 vs 1.9 + /- 0.3 microU/mL , respectively ; P < .05 ) , especially in male patients ( -41 + /- 9.2 vs 85 + /- 11.7 mg/dL and -2.7 + /- 0.2 vs 3.1 + /- 0.3 microU/mL , respectively ; P < .01 ) , at the end of the study . Lower glycosylated hemoglobin was observed in chromium-treated male patients ( -1.1 + /- 0 . 5 vs 0.7 + /- 0 . 2 ; P < .05 ) . However , there were no significant changes in other metabolic parameters ( lipid profiles including total cholesterol , triglyceride , low-density lipoprotein cholesterol , and high-density lipoprotein cholesterol ) , except improvement of insulin resistance ( homeostasis model assessment for insulin resistance and insulin sensitivity index from frequently sample d intravenous glucose tolerance test ) observed in male patients ( -2.1 + /- 1.1 vs -0.41 + /- 1.12 and 0.18 + /- 0.11 vs -0.15 + /- 0 . 2 , respectively ; P < .05 ) . There were no adverse events in both groups , except for mild complaints in the chromium group on constipation ( 5 % ) and flatulence ( 5 % ) . Intake of milk powder containing 400 microg/d of chromium for 16 weeks in subjects with type 2 diabetes mellitus result ed in lowering of FPG , fasting insulin , and improvement of metabolic control in male patients Macular degeneration associated with age and drusen , an important cause of severe visual loss in older persons , is of unknown cause . The sensory retina and retinal pigment epithelium , which are cell layers in zinc , appear to be prominently involved in the disease process . Because zinc plays a role in the metabolic function of several important enzymes in the chorioretinal complex , we undertook a prospect i ve , r and omized , double-masked , placebo-controlled investigation of the effects of oral zinc administration on the visual acuity outcome in 151 subjects with drusen or macular degeneration . Although some eyes in the zinc-treated group lost vision , this group had significantly less visual loss than the placebo group after a follow-up of 12 to 24 months . This is the first controlled oral intervention study to show a positive , if limited , treatment effect in macular degeneration , a major public health problem . Because of the pilot nature of the study and the possible toxic effects and complications of oral zinc administration , widespread use of zinc in macular degeneration is not now warranted Our investigations carried out in patients with diabetes mellitus revealed oxidative stress loads . The study presented here was to clarify whether a therapy with antioxidants can contribute to an improvement of prognosis .  80 patients affected with a long term diabetic late syndrome were r and omised and arranged to 4 groups of n = 20 each . In contrast to a control group these patients received 600 mg of alpha lipoic acid or 100 micrograms of selenium ( sodium selenite ) daily or 1200 IE of D-alpha-tocopherol respectively for a time of 3 months . In comparison with the control group all groups treated in an antioxidative way showed significantly diminished serum concentrations of thiobarbituric acid reactive substances and of urinary albumin excretion rates . The symptoms of distal symmetric neuropathy measured according to the thermo- and vibration sensitivity also improved in a highly significant manner . The results prove that oxidative stress plays a promoting role in developing of long term diabetic late complications and that a therapy with adjuvant antioxidants may lead to a regression of diabetic late complications The effect of magnesium ( Mg ) and ascorbic acid ( AA ) supplementation on metabolic control was assessed in 56 outpatient diabetics . A 90-day run-in period was followed by two 90-day treatment periods , during which Mg ( 600 mg/day ) and AA ( 2 g/day ) were administered in a r and omized double-blind cross-over fashion . A decrease in systolic and diastolic blood pressure ( 132 + /- 3 vs. 138 + /- 4 and 77 + /- 2 vs. 82 + /- 2 mm Hg ; p < 0.05 ) was observed in insulin-dependent diabetes mellitus subjects during Mg supplementation . No beneficial effect of Mg supplementation was observed on glycemic control , lipids or blood pressure in non-insulin-dependent diabetes mellitus ( NIDDM ) subjects . AA supplementation improved glycemic control among NIDDM subjects and both fasting blood glucose ( 9.1 + /- 0.5 vs. 10.1 + /- 0.6 mmol/l ; p < 0.05 ) and HbA1c ( 8.5 + /- 0.3 vs. 9.3 + /- 0.3 % ; p < 0.05 ) improved . Beneficial effects of AA supplementation on cholesterol ( 5.9 + /- 0.2 vs. 6.2 + /- 0.2 mmol/l ; p < 0.05 ) and triglycerides ( 2.2 + /- 0.2 vs. 2.5 + /- 0.2 ; p < 0.05 ) were also observed in NIDDM subjects . The results suggest that high-dose AA supplementation may have a beneficial effect in NIDDM subjects on both glycemic control and blood lipids
target: The review of trials identifies positive effects of these nutrients on various outcome measures relating to insulin resistance and cardiovascular factors .
  A majority of the trials found a positive effect of chromium on fasting plasma glucose .
  Isoflavones were found to have a positive effect on insulin resistance and cardiovascular outcome measures , but only when combined with soy proteins .
  Vitamin E is reported to reduce oxidative stress at levels of 200 mg day(-1 ) or more
background: The role of nutritional supplementation is of increasing interest with regard to ocular disease .
  R and omised controlled trials have demonstrated the effectiveness of supplementation for age-related macular degeneration , and formulations are now being developed for use by people with diabetes and diabetic retinopathy .
  The aim of this review was to synthesis e the evidence for use of nutritional supplementation in type 2 diabetes .
  The potential role of alpha-lipoic acid , chromium , folic acid , isoflavones , magnesium , Pycnogenol , selenium , vitamin C , vitamin E , and zinc in the treatment of type 2 diabetes is discussed .