title: Effects of zinc and multimineral vitamin supplementation on glycemic and lipid control in adult diabetes Potential Antioxidant Effects of Zinc and Chromium Supplementation in People with Type 2 Diabetes Mellitus Short-term zinc supplementation in women with non-insulin-dependent diabetes mellitus: effects on plasma 5'-nucleotidase activities, insulin-like growth factor I concentrations, and lipoprotein oxidation rates in vitro. Lipid peroxidation in insulin-dependent diabetic patients with early retina degenerative lesions: effects of an oral zinc supplementation. The Impact of Vitamins and/or Mineral Supplementation on Blood Pressure in Type 2 Diabetes Effects of melatonin and zinc on lipid profile and renal function in type 2 diabetic patients poorly controlled with metformin. Effects of combination of zinc and vitamin A supplementation on serum fasting blood sugar, insulin, apoprotein B and apoprotein A-I in patients with type I diabetes Comparison of the effects of vitamins and/or mineral supplementation on glomerular and tubular dysfunction in type 2 diabetes. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. A 5-Year Follow-Up of Antioxidant Supplementation in Type 2 Diabetic Retinopathy Contradicted and initially stronger effects in highly cited clinical research. Antioxidant effect of zinc in humans. Antioxidant Effects of Zinc Supplementation in Tunisians with Type 2 Diabetes Mellitus Serum zinc levels in diabetic patients and effect of zinc supplementation on glycemic control of type 2 diabetics. The impact of vitamin and/or mineral supplementation on lipid profiles in type 2 diabetes. Improving neuropathy scores in type 2 diabetic patients using micronutrients supplementation. Effect of zinc supplementation on microalbuminuria in patients with type 2 diabetes: a double blind, randomized, placebo-controlled, cross-over trial. Oral zinc therapy in diabetic neuropathy. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Effect of zinc supplementation on serum homocysteine in type 2 diabetic patients with microalbuminuria.
abstract: Aims : To evaluate the effects of zinc with or without other antioxidants on blood glucose , lipid profile , and serum creatinine in adult diabetics on long-term follow-up . Material s and methods : Patients ( n = 96 ) were r and omly allocated to three groups : group A ( n = 29 ) was supplemented with oral zinc sulfate ( 22 mg/day ) and multivitamin/mineral ( zinc+MVM ) preparation ; group B ( n = 31 ) was given the same preparation without zinc ( MVM ) ; and group C ( n = 36 ) was given a matching placebo for a period of 4 months in a single-blinded study . Blood sample s were taken at baseline and after 4 months of supplementation to assess blood glucose ( fasting and postpr and ial ) and glycosylated hemoglobin ( HbA1C% ) and serum levels of zinc , creatinine , and lipids . Results : The zinc+MVM group had a mean change of fasting blood sugar −0.33 mmol/L ( st and ard error of the mean 0.21 mmol/L ) and was significant ( P = 0.05 ) when compared with the other two groups ( mean change in the MVM group + 0.19 ( 0.31 ) mmol/L and + 0.43 ( 0.23 ) mmol/L in the control group , respectively ) . The HbA1C% level reduced significantly , irrespective of the baseline level , in zinc+MVM-supplemented individuals . In the other two groups , the change of HbA1C% level was not significant . Serum lipid levels reduced significantly in the zinc+MVM and MVM groups . Conclusions : Zinc+MVM supplementation showed beneficial effects in the metabolic control of adult diabetics in addition to elevating their serum zinc level . Zinc supplementation  improved glycemic control measured by HbA1C% and fasting and postpr and ial glucose . Furthermore , zinc supplementation  lowered serum cholesterol and cholesterol/high-density lipoprotein ratio 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 Non-insulin-dependent diabetes mellitus ( NIDDM ) may cause vulnerability to moderate zinc deficiency . In this study , short-term zinc supplementation ( 30 mg/d as amino acid chelate for 3 wk ) elevated plasma zinc and activities of 5'-nucleotidase , a zinc-dependant enzyme , in 20 postmenopausal women with NIDDM .  Placebo , given to 20 other women with NIDDM , had no effects on these indexes nor on any others taken in this study . Although zinc supplementation doubled the mean value for 5'-nucleotidase activity , values were still significantly lower than those of age-matched control subjects . Plasma insulin-like growth factor I concentrations increased with zinc treatment if starting concentrations were < 165 microg/L but were unchanged if they were > 165 microg/L. Lipoprotein oxidation in vitro , which has abnormal lag times and propagation rates for subjects with NIDDM and for moderately zinc-deficient rats , were unchanged by zinc supplementation . Possibly , this lack of effect occurred because the zinc treatment did not normalize zinc status . In conclusion , this study supports the contention that moderate zinc deficiency occurs frequently in subjects with NIDDM DESIGN Placebo for 3 months , followed by 30 mg/day zinc gluconate in identical capsules . SETTING Diabetic out patients clinic at the University Hospital , Grenoble . SUBJECTS Diabetic patients cared for type I diabetes mellitus . 22 patients began the study , 4 dropped out . 10 patients suffered of an early retinopathy , 8 patients had no retinopathy . INTERVENTIONS In this order : T0 biological measurements , 3 months placebo treatment , T1 biological measurements , 3 months zinc gluconate treatment , T2 biological measurements . Plasma Zn , Cu , Se , thiobarbituric acid reactants and antioxidant enzymes were measured [ plasma and red glutathione peroxidase ( Se-GPx ) , red cell superoxide dismutase ( Cu-Zn-SOD ) ] . RESULTS Lower plasma zinc level in the two groups . An increase in zinc level was observed and was more important in diabetic patients with no retinopathy ( P = 0.05 ) . The thiobarbituric acid reactants were above the reference values in all the patients , and were decreased at T2 ( P < 0.05 ) . Increase of GPx activity after zinc supplementation in patients with retinopathy . CONCLUSIONS Zinc deficiency in insulin-dependent diabetic patients is corrected by a zinc supplementation . Moreover this supplementation decreases lipid peroxidation . The effects of zinc are different in diabetic patients with or without retinopathy . The increase in Se-GPx activity observed in patients with retinopathy could be linked to the protective effect of zinc on the protein itself Objective : The present study design ed to assess the effect of Mg+Zn , vitamin C+E , and combination of these micronutrients on blood pressure in type 2 diabetic patients . Material s and Methods : In a r and omized , double-blind , placebo controlled clinical trial , 69 type 2 diabetic patients were r and omly divided into four groups , each group receiving one of the following daily supplement for three months ; group M : 200 mg Mg and 30 mg Zn ( n = 16 ) , group V : 200 mg vitamin C and 150 mg vitamin E ( n = 18 ) , group MV : minerals plus vitamins ( n = 17 ) , group P : placebo ( n = 18 ) . Blood pressure was measured at the beginning and at the end of the trial . Treatment effects were analyzed by general linear modeling . Results : Results indicate that after three months of supplementation  levels of systolic , diastolic and mean blood pressure decreased significantly in the MV group by 8 mmHg ( 122 ± 16 vs. 130 ± 19 mmHg ) , 6 mmHg ( 77 ± 9 vs. 83 ± 11 mmHg ) , and 7 mmHg ( 92 ± 9 vs. 99 ± 13 mmHg ) , respectively ( p < 0.05 ) . Also combination of vitamin and mineral supplementation had significantly effects in increasing serum potassium ( p < 0.05 ) and in decreasing serum malondialdehyde ( p < 0.05 ) . There was no significant change in the levels of these parameters in the other three groups . Conclusion : The results of the present study indicated that in type 2 diabetic patients  a combination of vitamins and minerals , rather than vitamin C and E or Mg and Zn , might decrease blood pressure Glycemic control and prevention of secondary complications are the most important goals of using pharmacologic treatment of diabetes mellitus ( DM ) . The inadequate responses to oral hypoglycemic agents may be attributed to inadequate postreceptor events even when insulin levels are quite sufficient , and associated with oxidative stress induced by long-term hyperglycemia . The administration of antioxidants such as melatonin and zinc may improve tissue responses to insulin and increase the efficacy of drugs , e.g. metformin , which act through this pathway . This project was design ed to evaluate the effects of melatonin and zinc on the lipid profile and renal function in type 2 DM patients poorly controlled with metformin .  A placebo-controlled , double-blind clinical trial was performed in which 46 type 2 diabetic patients were selected and allocated into three groups . These groups were treated with single daily oral doses of both 10 mg of melatonin and 50 mg of zinc acetate alone : 10 mg of melatonin and 50 mg of zinc acetate in addition to the regularly used metformin or placebo , given at bedtime for 90 days . Fasting lipid profiles and microalbuminuria ( MAU ) were measured before initiating the treatments ( zero time ) and after 30 and 90 days of treatment . Daily administration of melatonin and zinc improved the impaired lipid profile and decreased the level of MAU ; the addition of this treatment regimen in combination with metformin improved the tissue responses to this oral hypoglycemic agent . In conclusion , the combination of melatonin and zinc acetate , when used alone or in combination with metformin , improves DM-related complications such as the impaired lipid profile and MAU in type 2 DM patients Background and aim There is accumulating evidence that shows the metabolism of zinc and vitamin A are altered in diabetes mellitus type I ( DMTI ) , thus the present study was conducted to evaluate the effects of combination of zinc and vitamin A supplementation on serum fasting blood sugar ( FBS ) , insulin , apoprotein B and apoprotein A-I in patients with DMTI . Design Forty-eight , 7-year-old to 20-year-old patients with at least 2 years of DMTI history , without any metabolic condition or medicine intake with insulin treatment , participated in a r and omized double-blind clinical trial for 12 weeks . They were divided into zinc and vitamin A (VAZ)-supplemented ( 10 mg elemental zinc per day and one-half of a 25,000 IU vitamin A tablet every other day ) and /or placebo groups after matching for sex , age and DMTI duration . Nutrient intake was estimated using 24 h recall and was analyzed by food processor program . Serum apoproteins B and A-I , FBS and insulin levels were determined at the beginning and end of the trial . Results There was significant increase in apoprotein A-I ( P < 0.0001 ) and a significant decrease in apoprotein B ( P < 0.0001 ) and apoprotein B/apoprotein A-I ratio ( P < 0.0001 ) at the end of the study compared with baseline values in the VAZ group but apoprotein A-I had a significant increase ( P < 0.0001 ) and the apoprotein B/apoprotein A-I ratio had a significant decrease ( P = 0.02 ) at the end of study in the VAZ group compared with the control group Conclusion It seems that combined zinc and vitamin A supplementation can improve serum apoprotein A-I , apoprotein B and the apoprotein B/apoprotein A-I ratio in patients with DMTI OBJECTIVE The present study was design ed to assess the effect of magnesium plus zinc , vitamins C plus E , and a combination of these micronutrients on nephropathy indexes in type 2 diabetic patients . RESEARCH DESIGN AND METHODS In a r and omized , double-blind , placebo-controlled clinical trial , 69 type 2 diabetic patients were r and omly divided into four groups , each group receiving one of the following daily supplement for 3 months : group M ( n = 16 ) , 200 mg Mg and 30 mg Zn ; group V ( n = 18 ) , 200 mg vitamin C and 100 IU vitamin E ; group MV ( n = 17 ) , minerals plus vitamins ; and group P ( n = 18 ) , placebo .  Urinary albumin excretion and N-acetyl-beta-d-glucosaminidase activity ( NAG ) in urine were determined at the beginning and at the end of the trial . Treatment effects were analyzed by general linear modeling . RESULTS Results indicate that after 3 months of supplementation , levels of urinary albumin excretion decreased in the V and MV groups ( P = 0.034 and P = 0.005 , respectively ) . Urinary NAG activity did not significantly change in any treatment groups . Levels of systolic , diastolic , and mean blood pressure significantly decreased in the MV group ( P = 0.008 , P = 0.017 , and P = 0.009 , respectively ) . Also , combination of vitamin and mineral supplementation had significant effects in decreasing fasting serum glucose ( P = 0.035 ) and malondialdehyde concentrations ( P = 0.004 ) and in increasing HDL cholesterol and apolipoprotein A1 levels ( P = 0.019 ) . There was no significant change in the levels of these parameters in the other three groups . CONCLUSIONS In conclusion , the results of the present study provide evidence for the effects of vitamins C and E and also combination of magnesium , zinc , and vitamins C and E supplementation on improvement of glomerular but not tubular renal function in type 2 diabetic patients OBJECTIVE This study evaluated the effects of exenatide , a novel incretin mimetic , in hyperglycemic patients with type 2 diabetes unable to achieve glycemic control with metformin-sulfonylurea combination therapy .  RESEARCH DESIGN AND METHODS A 30-week , double-blind , placebo-controlled study was performed in 733 subjects ( aged 55 + /- 10 years , BMI 33.6 + /- 5.7 kg/m(2 ) , A1C 8.5 + /- 1.0 % ; means + /- SD ) r and omized to 5 microg subcutaneous exenatide b.i.d . ( arms A and B ) or placebo  for 4 weeks . Thereafter , arm A remained at 5 microg b.i.d . and arm B escalated to 10 microg b.i.d . Subjects continued taking their dose of metformin and were r and omized to either maximally effective ( MAX ) or minimum recommended ( MIN ) doses of sulfonylurea . RESULTS Week 30 A1C changes from baseline ( + /-SE ) were -0.8 + /- 0.1 % ( 10 microg ) , -0.6 + /- 0.1 % ( 5 microg ) , and + 0.2 + /- 0.1 % ( placebo ; adjusted P < 0.0001 vs. placebo ) , yielding placebo-adjusted reductions of -1.0 % ( 10 microg ) and -0.8 % ( 5 microg ) . In the evaluable population , exenatide-treated subjects were more likely to achieve A1C < or = 7 % than placebo-treated subjects ( 34 % [ 10 microg ] , 27 % [ 5 microg ] , and 9 % [ placebo ] ; P < 0.0001 ) . Both exenatide arms demonstrated significant weight loss ( -1.6 + /- 0.2 kg from baseline each exenatide arm , -0.9 + /- 0.2 kg placebo ; P < or = 0.01 vs. placebo ) . Mild or moderate nausea was the most frequent adverse event . The incidence of mild/moderate hypoglycemia was 28 % ( 10 microg ) , 19 % ( 5 microg ) , and 13 % ( placebo ) and appeared lower with MIN than with MAX sulfonylurea treatment . CONCLUSIONS Exenatide significantly reduced A1C in patients with type 2 diabetes unable to achieve adequate glycemic control with maximally effective doses of combined metformin-sulfonylurea therapy . This improvement in glycemic control was associated with no weight gain and was generally well tolerated Purpose This study was design ed to evaluate the effect of antioxidant supplementation on  diabetic retinopathy ( DR )  over a 5-year follow-up period . To our knowledge , this is the first such clinical trial performed . Methods We recruited 105 type 2 diabetic patients with nonproliferative DR . A complete ophthalmic checkup and a plasma determination of oxidative ( malonyldialdehyde [ MDA ] ) and antioxidant parameters ( total antioxidant status [ TAS ] ) were obtained as the baseline . One part of the cohort was r and omly assigned to oral antioxidant supplementation at nutritional doses . The same examinations were performed with 97 diabetic patients who completed the 5-year follow-up period . The best-corrected visual acuity , DR score , MDA , and TAS values were compared at the beginning and the end of the follow-up . Results Best-corrected visual acuity did not change during the follow-up , irrespective of supplementation . However , the retinopathy stage showed a retardation of progression in the subgroup with supplementation , but worsened in the subgroup with no antioxidant supplementation . Furthermore , the antioxidant supplementation group maintained its antioxidant plasma status levels , which was related to decreased oxidative plasma activity . Conclusions Oral antioxidant supplementation could be a useful adjunctive long-term therapy in the treatment of nonproliferative DR CONTEXT Controversy and uncertainty ensue when the results of clinical research on the effectiveness of interventions are subsequently contradicted . Controversies are most prominent when high-impact research is involved . OBJECTIVES To underst and how frequently highly cited studies are contradicted or find effects that are stronger than in other similar studies and to discern whether specific characteristics are associated with such refutation over time . DESIGN All original clinical research studies published in 3 major general clinical journals or high-impact-factor specialty journals in 1990 - 2003 and cited more than 1000 times in the literature were examined . MAIN OUTCOME MEASURE The results of highly cited articles were compared against subsequent studies of comparable or larger sample size and similar or better controlled design s. The same analysis was also performed comparatively for matched studies that were not so highly cited . RESULTS Of 49 highly cited original clinical research studies , 45 cl aim ed that the intervention was effective .  Of these , 7 ( 16 % ) were contradicted by subsequent studies , 7 others ( 16 % ) had found effects that were stronger than those of subsequent studies , 20 ( 44 % ) were replicated , and 11 ( 24 % ) remained largely unchallenged . Five of 6 highly-cited nonr and omized studies had been contradicted or had found stronger effects vs 9 of 39 r and omized controlled trials ( P = .008 ) . Among r and omized trials , studies with contradicted or stronger effects were smaller ( P = .009 ) than replicated or unchallenged studies although there was no statistically significant difference in their early or overall citation impact . Matched control studies did not have a significantly different share of refuted results than highly cited studies , but they included more studies with " negative " results . CONCLUSIONS Contradiction and initially stronger effects are not unusual in highly cited research of clinical interventions and their outcomes . The extent to which high citations may provoke contradictions and vice versa needs more study . Controversies are most common with highly cited nonr and omized studies , but even the most highly cited r and omized trials may be challenged and refuted over time , especially small ones Oxidative stress is known to be an important contributing factor in many chronic diseases . We tested the hypothesis that in healthy normal volunteers zinc acts as an effective anti-inflammatory and antioxidant agent .  Ten normal volunteers were administered daily  oral zinc supplementation ( 45 mg zinc as gluconate ) and 10 volunteers received placebo for 8 weeks . Plasma zinc , MDA , HAE , and 8-OHdG levels ; LPS-induced TNF-alpha and IL-1beta mRNA ; and ex vivo TNF-alpha-induced NF-kappaB activity in mononuclear cells ( MNC ) were determined before and after supplementation . In subjects receiving zinc , plasma levels of lipid peroxidation products and DNA adducts were decreased , whereas no change was observed in the placebo group . LPS-stimulated MNC isolated from zinc-supplemented subjects showed reduced mRNA for TNF-alpha and IL-1beta compared to placebo . Ex vivo , zinc protected MNC from TNF-alpha-induced NF-kappaB activation . In parallel studies using HL-60 , a promyelocytic cell line , we observed that zinc enhances the upregulation of mRNA and DNA-specific binding for A20 , a transactivating factor which inhibits the activation of NF-kappaB. Our results suggest that zinc supplementation may lead to downregulation of the inflammatory cytokines through upregulation of the negative feedback loop A20 to inhibit induced NF-kappaB activation . Zinc administration to human subjects with conditions associated with increased oxidative stress should be explored Objective : To determine the effects of zinc ( Zn ) supplementation on oxidative stress in persons with type 2 diabetes mellitus ( type 2 DM ) . Design : Tunisian adult subjects with HbA1c > 7.5 % were supplemented for six months with 30 mg/day of Zn as Zn gluconate or placebo . The effects of supplementation on plasma zinc ( Zn ) , copper ( Cu ) , urinary Zn , plasma thiobarbituric acid reactive substances ( TBARS ) , Cu-Zn superoxide dismutase ( SOD ) and glutathione peroxidase activities ( GPX ) in red blood cells , blood lipids and lipoproteins , HbA1c and fasting glucose were measured at the beginning of the study and after three and six months . Results : At the beginning of the study , more than 30 % of the subjects exhibited plasma Zn values less than the normal minimum of 10.7 μmol/L , whereas levels of plasma Cu and antioxidant RBC Cu-Zn SOD and GPx enzyme activities were in the normal ranges . Oxidative stress , monitored by plasma TBARS , was increased in individuals with diabetes compared with healthy Tunisian subjects ( 3.32 ± 0.05 μmol/L vs. 2.08 ± 0.04 μmol/L ) and an inverse correlation was found between Zn plasma levels and plasma TBARS . After three and six months of Zn supplementation , all of the subjects exhibited plasma Zn values greater than 10.7 μmol/L. There was a decrease of plasma TBARS in Zn supplemented group after six months ( 15 % ) with no significant changes in the placebo group . Supplementation did not alter significantly HbA1c nor glucose homeostasis . No adverse effects of Zn supplementation were observed on Cu status or HDL cholesterol . Conclusions : These data suggest the potential beneficial antioxidant effects of Zn supplementation in persons with type 2 DM . These results are particularly important in light of the deleterious consequences of oxidative stress in persons with diabetes OBJECTIVE The present study is an attempt to assess serum zinc level in a sample of diabetic patients ( both type 1 and type 2 diabetics ) in comparison with those of apparently healthy controls , and to ascertain the relationship between the levels of serum zinc with some epidemiological variables . Furthermore , a trial of zinc supplementation for 3 months conducted to assess the effect of zinc supplementation on glycemic control of the studied type 2 diabetic patients , and the factors that affect the response to this supplementation . METHODS Collection of data was carried out during the period between November 2002 to February 2003 at the Diabetic Center of Merjan Teaching Hospital in Babil Governorate , Iraq . In the first part of the study ( a case-control study ) , the diabetic group included 133 diabetic patients ( type 1 and 2 ) who were chosen from patients attending the Diabetic Center during the period of the study . The control group included 133 apparently healthy subjects who were selected from the workers of the same hospital . Selection of cases and controls was carried out by using systematic r and om sampling procedure . In the second part of the study ( single blind were intervention study ) , type 2 diabetic patients ( 101 patients ) divided into 2 groups ; the first group included 50 patients supplemented with oral zinc sulfate ( 30 mg of elemental zinc/cap/day ) for 3 months and second group included 51 patients given placebo and design ed as control group . RESULTS The first part of the study shows that the mean value for serum zinc level was significantly lower in diabetic patients than healthy controls ( 64.2 + /- 12.6 microg/dl for type 1 diabetics , and 68.9 + /- 11.9 microg/dl for type 2 diabetics versus 83.4 + /- 12.5 microg/dl for healthy controls ) . Using simple linear regression , significant positive correlation was found between serum zinc level and years of education and significant negative correlation was found between serum zinc level and baseline HbA1c% value , in the diabetic group . While significant positive correlation found between serum zinc level and estimated zinc intake in the control group . Using multiple regression analysis , serum zinc level showed significant positive correlation with gender ( being a male compared with female ) , and estimated zinc intake and significant negative correlation with diabetes state ( diabetic compared with non-diabetic ) , residence ( urban compared with rural residents ) , and plant protein intake . The second part of the study shows that the mean value for HbA1c% concentration of the supplemented group decreased significantly at the end of the 3 months of follow up , while no significant changes were found in the mean value for HbA1c% of the control group . The present study showed that the change in HbA1c% after supplementation had significant negative correlation with baseline HbA1c% value . CONCLUSION Diabetic patients have significantly lower mean serum zinc levels compared with healthy controls . Zinc supplementation for type-2 diabetics has beneficial effects in elevating their serum zinc level , and in improving their glycemic control that is shown by decreasing their HbA1c% concentration OBJECTIVE The purpose of the present study was to assess the impact of Mg + Zn , Vitamins C + E , and combination of these micronutrients on serum lipid and lipoprotein profiles in type 2 diabetic patients . MATERIAL S AND METHODS In a r and omized , double-blind , placebo controlled clinical trial , 69 type 2 diabetic patients were r and omly divided into four groups , each group receiving one of the following daily supplement for 3 months ; group M : 200 mg Mg and 30 mg Zn ( n = 16 ) , group V : 200 mg Vitamin C and 150 mg Vitamin E ( n = 18 ) , group MV : minerals plus vitamins ( n = 17 ) , group P : placebo ( n = 18 ) . Fasting blood and urine sample s were collected at the beginning and at the end of the trial . Serum triglyceride , total cholesterol , high density lipoprotein cholesterol ( HDL-c ) and low density lipoprotein cholesterol ( LDL-c ) were measured enzymatically . Apolipoproteins ( apo ) A1 and B were measured by immunoturbidimetric method . Adjustment for differences in baselines covariates and changes in variables during study were performed by analysis of covariance using general linear models . RESULTS Results indicate that after 3 months of supplementation mean serum levels of HDL-c and apo A1 increased significantly in the MV group by 24 % ( 50.4 + /-19.3 mg/dl versus 40.6 + /- 10.8 mg/dl ) and 8.8 % ( 169.8 + /- 33.8 mg/dl versus 156.1 + /- 23.9 mg/dl ) , respectively ( P < 0.01 ) . There were no significant changes in the levels of these parameters in the other three groups . Serum levels of total cholesterol , LDL-c , triglyceride , and apo B were not altered after supplementation in all four groups . CONCLUSION It is concluded that since co-supplementation of Mg , Zn , Vitamins C and E significantly increases HDL-c and apo A1 , supplementation of these micronutrients could be recommended for the type 2 diabetic patients based on their daily requirements AIM The aim of the present study was to determine if micronutrients supplementation can improve neuropathy indices in type 2 diabetes . MATERIAL S AND METHODS In this r and omized , double-blind , placebo-controlled clinical trial , 75 type 2 diabetes patients were assigned to three treatment groups , receiving one of the following daily supplement for 4 months : Group MV : zinc ( 20 mg ) , magnesium ( 250 mg ) , vitamin C ( 200 mg ) and E ( 100 mg ) ; Group MVB : both of the above mineral and vitamin supplements plus vitamin B1 ( 10 mg ) , B2 ( 10 mg ) , B6 ( 10 mg ) , biotin ( 200 μg ) , B12 ( 10 μg ) and folic acid ( 1 mg ) ; Group P : placebo . RESULTS 67 patients completed the study . Neuropathic symptoms based on the MNSI question naire improved from 3.45 to 0.64 ( p=0.001 ) in group MVB , from 3.96 to 1.0 ( p=0.001 ) in group MV and from 2.54 to 1.95 in placebo group after 4 months . There was no significant difference between three treatment groups in MNSI examinations after 4 months supplementations . Over 4 months of treatment , patients showed no significant changes in glycemic control , capillary blood flow or electrophysiological measures in MV and MVB groups compared with placebo group . CONCLUSIONS These studies suggest that micronutrients supplementation might ameliorate diabetic neuropathy symptoms OBJECTIVES Oxidative stress can contribute to microvascular complications in diabetes . A decisive event associated with this condition may be the decrease in the synthesis of zinc-containing antioxidant enzymes such as superoxide dismutase and glutathione peroxidase . This consideration led us to investigate the effect of zinc supplementation versus placebo on microalbuminuria in diabetic patients in a r and omized double blind clinical trial . METHODS Fifty diabetic patients with microalbuminuria were enrolled .  Fasting plasma glucose , HbA1c , lipid profiles , plasma zinc levels and r and om urine for albumin and creatinine were measured . Patients r and omly received 30 mg elemental zinc ( group 1 ) or placebo ( group 2 ) for 3 months . After a 4 week wash-out period , the groups were crossed over ( i.e. the zinc group were given placebo , and the placebo group were given zinc ) and the protocol was repeated . RESULTS From an initial number of 50 selected patients ( 25 in each of two groups ) , 39 patients ( 21 in group 1 and 18 in group 2 ) completed the study . In group 1 , after zinc supplementation , urinary albumin excretion decreased significantly from 86.5 + /- 57 to 75 + /- 71 mg/g ( p = 0.01 ) . After placebo , patients in group 1 showed no significant reduction in microalbuminuria ( 85 + /- 72 mg/g to 83 + /- 63 mg/g creatinine ) . In group 2 , no change in albumin excretion was observed after placebo treatment ( 90.5 + /- 63 mg/g to 90 + /- 60 mg/g creatinine ) . After zinc supplementation , a significant reduction was observed in albumin excretion , from 90 + /- 60 mg/g to 85 + /- 57 mg/g creatinine ( p = 0.003 ) . CONCLUSIONS Zinc supplementation reduced albumin excretion in microalbuminuric type 2diabetic patients . This outcome may be due to the antioxidant effect of zinc The present double blind r and omized study was conducted on 50 subjects ; 20 age and sex matched healthy controls ( Group -- I ) ; 15 patients of diabetes mellitus with neuropathy who received placebo for 6 weeks ( Group -- IIA ) ; and 15 patients of diabetes mellitus with neuropathy who were given supplemental zinc sulphate ( 660 mg ) for 6 weeks ( Group -- IIB ) .  Serum zinc level , fasting blood sugar ( FBS ) and post pr and ial blood sugar ( PPBS ) levels and motor nerve conduction velocity ( MNCV ) were estimated on day 0 and after 6 weeks in all subjects . Serum zinc levels were significantly low ( p < 0.001 ) in group IIA and IIB as compared to healthy controls ( Group -- I ) at baseline . After 6 weeks the change in pre and post therapy values of FBS , PPBS and MNCV ( median and common peroneal nerve ) were highly significant ( P = < 0.001 ) for group IIB alone with insignificant change ( P = > 0.05 ) in group IIA . No improvement ( P = > 0.05 ) in autonomic dysfunction was observed in either groups . Therefore , oral zinc supplementation helps in achieving better glycemic control and improvement in severity of peripheral neuropathy as assessed by MNCV BACKGROUND Observational and experimental data suggest that antioxidant and /or zinc supplements may delay progression of age-related macular degeneration ( AMD ) and vision loss . OBJECTIVE To evaluate the effect of high-dose vitamins C and E , beta carotene , and zinc supplements on AMD progression and visual acuity . DESIGN The Age-Related Eye Disease Study , an 11-center double-masked clinical trial , enrolled participants in an AMD trial if they had extensive small drusen , intermediate drusen , large drusen , non central geographic atrophy , or pigment abnormalities in 1 or both eyes , or advanced AMD or vision loss due to AMD in 1 eye . At least 1 eye had best-corrected visual acuity of 20/32 or better . Participants were r and omly assigned to receive daily oral tablets containing : ( 1 ) antioxidants ( vitamin C , 500 mg ; vitamin E , 400 IU ; and beta carotene , 15 mg ) ; ( 2 ) zinc , 80 mg , as zinc oxide and copper , 2 mg , as cupric oxide ; ( 3 ) antioxidants plus zinc ; or ( 4 ) placebo . MAIN OUTCOME MEASURES ( 1 ) Photographic assessment of progression to or treatment for advanced AMD and ( 2 ) at least moderate visual acuity loss from baseline ( > or = 15 letters ) . Primary analyses used repeated- measures logistic regression with a significance level of.01 , unadjusted for covariates . Serum level measurements , medical histories , and mortality rates were used for safety monitoring . RESULTS Average follow-up of the 3640 enrolled study participants , aged 55 - 80 years , was 6.3 years , with 2.4 % lost to follow-up . Comparison with placebo demonstrated a statistically significant odds reduction for the development of advanced AMD with antioxidants plus zinc ( odds ratio [ OR ] , 0.72 ; 99 % confidence interval [ CI ] , 0.52 - 0.98 ) . The ORs for zinc alone and antioxidants alone are 0.75 ( 99 % CI , 0.55 - 1.03 ) and 0.80 ( 99 % CI , 0.59 - 1.09 ) , respectively . Participants with extensive small drusen , nonextensive intermediate size drusen , or pigment abnormalities had only a 1.3 % 5-year probability of progression to advanced AMD . Odds reduction estimates increased when these 1063 participants were excluded  ( antioxidants plus zinc : OR , 0.66 ; 99 % CI , 0.47 - 0.91 ; zinc : OR , 0.71 ; 99 % CI , 0.52 - 0.99 ; antioxidants : OR , 0.76 ; 99 % CI , 0.55 - 1.05 ) . Both zinc and antioxidants plus zinc significantly reduced the odds of developing advanced AMD in this higher-risk group . The only statistically significant reduction in rates of at least moderate visual acuity loss occurred in persons assigned to receive antioxidants plus zinc ( OR , 0.73 ; 99 % CI , 0.54 - 0.99 ) . No statistically significant serious adverse effect was associated with any of the formulations . CONCLUSIONS Persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced AMD . Those with extensive intermediate size drusen , at least 1 large druse , non central geographic atrophy in 1 or both eyes , or advanced AMD or vision loss due to AMD in 1 eye , and without contraindications such as smoking , should consider taking a supplement of antioxidants plus zinc such as that used in this study OBJECTIVES Elevated homocysteine levels are considered to be an independent risk factor for cardiovascular complications in diabetic patients . The aim of this study was to find out if zinc supplementation improves homocysteine levels , which may exert vascular-protective effects in type 2 diabetes subjects with microalbuminuria . METHODS In a r and omized , double-blind , controlled , crossover study , 50 type 2 diabetic patients with microalbuminuria were subdivided into two groups and supplemented with 30 mg/d of zinc ( group 1 ) or placebo ( group 2 ) for three months with a four-week wash out period . Serum creatinine , vitamin B(12 ) , folate , fasting plasma glucose , HbA1c , lipid profiles , zinc , homocysteine levels and r and om urine albumin were measured before and after the first and second phase of the study in all participants . RESULTS Mean serum zinc was significantly increased after zinc supplementation ( from 76 + /- 16 mug/dl to 93 + /- 20 microg/dl ; p < 0.05 ) , while there was no change in the placebo group ( 75 + /- 16 microg/dl to 75 + /- 15 microg/dl ) . With  zinc supplementation  , homocysteine levels reduced significantly ( from 13.71 + /- 3.84 mumol/l to 11.79 + /- 3.06 mumol/l ; p < 0.05 ) , which did not occur on placebo ( from 12.59 + /- 2.13 mumol/l to 13.36 + /- 2.03 mumol/l ) . Simple regression was used to show a positive correlation between urine albumin excretion and serum homocysteine ( r = 0.37 , p = 0.023 ) . Vitamin B(12 ) and folate levels increased significantly in patients who received zinc in comparison to those who received placebo . A negative correlation was observed between homocysteine and vitamin B(12 ) concentration ( r = -0.36 , p = 0.025 ) . CONCLUSION Zinc supplementation reduced serum homocysteine and increased vitamin B(12 ) and folate concentrations in type 2 diabetic patients with microalbuminuria
target: Studies have also shown a significant reduction in systolic and diastolic blood pressures after Zinc supplementation .
  This first comprehensive systematic review and meta- analysis on the effects of Zinc supplementation in patients with diabetes demonstrates that Zinc supplementation  has beneficial effects on glycaemic control and promotes healthy lipid parameters .
background: The number of people with diabetes and pre-diabetes are exponentially increasing .
  Studies on humans have shown the beneficial effects of Zinc supplementation in patients with diabetes .
  The present study aims to systematic ally evaluate the literature and meta-analyze the effects of Zinc supplementation on diabetes .