Antioxisant Tools. Resveratrol supplementation also had no effect on blood Antioxieant, Antioxidant supplements for diabetes management energy expenditure, oxidation rates diabbetes lipids, Citrus bioflavonoids and blood circulation or visceral Antioxieant content, Fat distribution and diet inflammatory and metabolic biomarkers. Analyses of manage,ent secondary endpoints of the study, which included total mortality, hospitalizations for heart failure and unstable angina, revascularization and nephropathy, were recently published [ 58 ], and again vitamin E supplementation for 4. These detrimental effects are briefly summarized in this section. Article CAS PubMed Google Scholar Touyz RM: Reactive oxygen species and angiotensin II signaling in vascular cells — implications in cardiovascular disease. Contact Us. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor s.

Antioxidant supplements for diabetes management -

SOD1, superoxide dismutase 1; SOD2, superoxide dismutase 2; KO, knockout; OE, overexpression; HFD, high-fat diet; Hz, heterozygous; ROS, reactive oxygen species; GPx, glutathione peroxidase; PTP, protein-tyrosine phosphatase; GRx, glutaredoxin; Prx, peroxiredoxin; STZ mice, streptozotocin-injected mice; Msr, methionine sulfoxide reductase; SelW, selenoprotein W.

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Review article Can antioxidants be effective therapeutics for type 2 diabetes? Soyoung Park , So-Young Park Yeungnam University Journal of Medicine ;38 2 Abstract The global obesity epidemic and the growing elderly population largely contribute to the increasing incidence of type 2 diabetes.

Insulin resistance acts as a critical link between the present obesity pandemic and type 2 diabetes. Naturally occurring reactive oxygen species ROS regulate intracellular signaling and are kept in balance by the antioxidant system.

However, the imbalance between ROS production and antioxidant capacity causes ROS accumulation and induces oxidative stress.

Oxidative stress interrupts insulin-mediated intracellular signaling pathways, as supported by studies involving genetic modification of antioxidant enzymes in experimental rodents. In addition, a close association between oxidative stress and insulin resistance has been reported in numerous human studies.

However, the controversial results with the use of antioxidants in type 2 diabetes raise the question of whether oxidative stress plays a critical role in insulin resistance.

In this review article, we discuss the relevance of oxidative stress to insulin resistance based on genetically modified animal models and human trials. Keywords : Antioxidants ; Insulin resistance ; Oxidative stress ; Reactive oxygen species. Intracellular reactive oxygen species ROS generation and the antioxidant scavenging system.

ROS is produced from mitochondria, peroxisome, nicotinamide-adenine dinucleotide phosphate NADPH oxidase, and xanthine oxidase. Among these sources, the mitochondrial electron transport chain is the primary source for ROS production.

Superoxide dismutase 2 SOD2 catalyzes the conversion of superoxide anion O 2 — into hydrogen peroxide H 2 O 2 in the mitochondria. The H 2 O 2 is then detoxified in the mitochondria or moves to the cytoplasm. Cytoplasmic superoxide anion is generated from NADPH oxidase and xanthine oxidase, and subsequently converted into H 2 O 2 by superoxide dismutase 1 SOD1.

Oxidized methionine Ox-Met is reduced by methionine sulfoxide reductase Msr to methionine Met. Nitric oxide NO reacts with superoxide anion to form peroxynitrite ONOO — , which is detoxified by Prx, GSH, and GPx. Intracellular insulin signaling pathway in skeletal muscle.

Binding of insulin to insulin receptors IR on the plasma membrane promotes tyrosine autophosphorylation at the IR, which in turn induces tyrosine phosphorylation of the IR substrate IRS. Activated AS increases glucose uptake by mediating the translocation of glucose transporter type 4 GLUT4 from the cytoplasm to the plasma membrane.

Intracellular glucose is used for adenosine triphosphate ATP generation and glycogen synthesis. Tyr, tyrosine; Ser, serine; PIP 2 , phosphatidylinositol 4,5-bisphosphate; PIP 3 , phosphatidylinositol 3,4,5 -triphosphate; PDK1, phosphatidylinositide-dependent protein kinase 1; mTORC2, mammalian target of rapamycin complex 2; FOXO1, forkhead box protein O1; GS, glycogen synthase; acetyl-CoA, acetyl coenzyme A; TCA, tricarboxylic acid cycle; ETC, electron transport chain; ROS, reactive oxygen species.

Inhibition of the insulin signaling pathway by oxidative stress. Reactive oxygen species ROS interferes with insulin action by altering several substrates of the insulin signaling pathway.

In addition, ROS suppresses glucose absorption by degrading glucose transporter type 4 GLUT4 in a casein kinase 2 CK2 -dependent manner. Reactive nitrogen species RNS inhibits tyrosine phosphorylation of IRS and protein kinase B AKT activation by inducing nitration of tyrosine.

Mitochondrial functional defects by ROS not only induce an explosive increase in oxidative stress but also suppress mitochondrial energy production, eventually leading to cell death. Tyr, tyrosine; Ser, serine; PIP 2 , phosphatidylinositol 4,5-bisphosphate; PIP 3 , phosphatidylinositol 3,4,5 -triphosphate; PI3K, phosphatidylinositol 3-kinases; PDK1, phosphatidylinositide-dependent protein kinase 1; mTORC2, mammalian target of rapamycin complex 2; FOXO1, forkhead box protein O1; GSK3, glycogen synthase kinase 3; AS, AKT substrate of kDa; acetyl-CoA, acetyl coenzyme A; mtDNA, mitochondrial DNA; TCA, tricarboxylic acid cycle; ETC, electron transport chain.

Table 1. The effect of deficiency or overexpression of antioxidant enzymes on glucose metabolism and insulin sensitivity in mice. Table 2.

Recruiting and not yet recruiting August clinical trials of agents with antioxidant properties targeting type 2 diabetes. The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol. Turko IV, Marcondes S, Murad F: Diabetes-associated nitration of tyrosine and inactivation of succinyl-CoAoxoacid CoA-transferase.

Am J Physiol Heart Circ Physiol. CAS PubMed Google Scholar. Maritim AC, Sanders RA, Watkins JB: Diabetes, oxidative stress, and antioxidants: A review. J Biochem Mol Toxicol. Evans JL, Goldfine ID, Maddux BA, Grodsky GM: Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes.

Endocr Rev. Vega-Lopez S, Devaraj S, Jialal I: Oxidative stress and antioxidant supplementation in the management of diabetic cardiovascular disease. J Investig Med. Evans JL, Goldfine ID, Maddux BA, Grodsky GM: Are oxidative stress-activated signaling pathways mediators of insulin resistance and {beta}-cell dysfunction?.

Griendling KK, FitzGerald GA: Oxidative stress and cardiovascular injury: Part I: Basic mechanisms and in vivo monitoring of ROS. Article PubMed Google Scholar. Griendling KK, FitzGerald GA: Oxidative stress and cardiovascular injury: Part II: animal and human studies.

Taniyama Y, Griendling KK: Reactive oxygen species in the vasculature: Molecular and cellular mechanisms. Boullier A, Bird DA, Chang MK, Dennis EA, Friedman P, Gillotre-Taylor K, Horkko S, Palinski W, Quehenberger O, Shaw P: Scavenger receptors, oxidized LDL, and atherosclerosis.

Ann N Y Acad Sci. Vascul Pharmacol. Circ Res. Soriano FG, Virag L, Szabo C: Diabetic endothelial dysfunction: role of reactive oxygen and nitrogen species production and poly ADP-ribose polymerase activation. J Mol Med. Oberg BP, McMenamin E, Lucas FL, McMonagle E, Morrow J, Ikizler TA, Himmelfarb J: Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease.

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Ceriello A, Mercuri F, Quagliaro L, Assaloni R, Motz E, Tonutti L, Taboga C: Detection of nitrotyrosine in the diabetic plasma: evidence of oxidative stress. Aliciguzel Y, Ozen I, Aslan M, Karayalcin U: Activities of xanthine oxidoreductase and antioxidant enzymes in different tissues of diabetic rats.

J Lab Clin Med. Kitada M, Koya D, Sugimoto T, Isono M, Araki S, Kashiwagi A, Haneda M: Translocation of glomerular p47phox and p67phox by protein kinase C-beta activation is required for oxidative stress in diabetic nephropathy.

Etoh T, Inoguchi T, Kakimoto M, Sonoda N, Kobayashi K, Kuroda J, Sumimoto H, Nawata H: Increased expression of NAD P H oxidase subunits, NOX4 and p22phox, in the kidney of streptozotocin-induced diabetic rats and its reversibity by interventive insulin treatment.

Ergul A, Schultz Johansen J, Stromhaug C, Harris AK, Hutchinson J, Tawfik A, Rahimi A, Rhim E, Wells B, Caldwell RW: Vascular dysfunction of venous bypass conduits is mediated by reactive oxygen species in diabetes: Role of endothelin J Pharmacol Exp Ther.

Green K, Brand MD, Murphy MP: Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP: Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage.

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Cristina Polidori M, Pratico D, Savino K, Rokach J, Stahl W, Mecocci P: Increased F2 isoprostane plasma levels in patients with congestive heart failure are correlated with antioxidant status and disease severity.

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Potential for effective therapeutic reduction in vascular oxidative stress. Watts GF, Playford DA, Croft KD, Ward NC, Mori TA, Burke V: Coenzyme Q 10 improves endothelial dysfunction of the brachial artery in Type II diabetes mellitus. Heller R, Unbehaun A, Schellenberg B, Mayer B, Werner-Felmayer G, Werner ER: L-ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterin.

J Biol Chem. Mekinova D, Chorvathova V, Volkovova K, Staruchova M, Grancicova E, Klvanoca J, Ondreicka R: Effect of intake of exogenous vitamins C, E and beta-carotene on the antioxidative status in kidneys of rats with streptozotocin-induced diabetes. Kedziora-kornatowska K, Szram S, Kornatowski T, Szadujkis-Szadurski L, Kedziora J, Bartosz G: Effect of vitamin E and vitamin C supplementation of antioxidative state and renal glomerular basement membrane thickness in diabetic kidney.

Exp Nephrology. Cinar M, Ulker S, Alper G, Evinc A: Effect of dietary vitamin E supplementation on vascular reactivity of thoracic aorta in streptozotocin-diabetic rats. Obrosova I, Fathallah L, Greene D: Early changes in lipid peroxidation and antioxidative defense in rat retina. Eur J Pharm.

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J Am Coll Cardiol. Beckman JA, Goldfine AB, Gordon MB, Garrett LA, Keaney JF, Creager MA: Oral antioxidant therapy improves endothelial function in Type 1 but not Type 2 diabetes mellitus.

Am J Physiol. Gaede P, Poulsen HE, Parving HH, Pedersen O: Double-blind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in Type 2 diabetic patients.

Diabet Med. Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P: Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. Boaz M, Smetana S, Weinstein T, Matas Z, Gafter U, Iaina A, Knecht A, Weissgarten Y, Brunner D, Fainaru M: Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease SPACE : randomised placebo-controlled trial.

Gaede P, Vedel P, Larsen N, Jensen GVH, Parving H-H, Pedersen O: Multifactorial intervention and cardiovascular disease in patients with Type 2 diabetes. Sacco M, Pellegrini F, Roncaglioni MC, Avanzini F, Tognoni G, Nicolucci A: Primary prevention of cardiovascular events with low-dose aspirin and Vitamin E in Type 2 diabetic patients: Results of the Primary Prevention Project PPP trial.

Lonn EM, Yusuf S, Dzavik V, Doris CI, Yi Q, Smith S, Moore-Cox A, Bosch J, Riley WA, Teo KK: Effects of ramipril and vitamin E on atherosclerosis : The study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E SECURE. Lonn E, Yusuf S, Hoogwerf B, Pogue J, Yi Q, Zinman B, Bosch J, Dagenais G, Mann JFE, Gerstein HC: Effects of vitamin E on cardiovascular and microvascular outcomes in high-risk patients with diabetes: Results of the HOPE study and MICRO-HOPE substudy.

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Download references. This work was supported by grants from NIH HL , American Heart Association Scientist Development Grant and American Diabetes Association to Adviye Ergul and an AHA Southeast Affiliate Predoctoral Fellowship Award to Alex K.

University of Georgia College of Pharmacy, Athens, Georgia, USA. Medical College of Georgia Vascular Biology Center, Augusta, Georgia, USA.

You can also search for this author in PubMed Google Scholar. Correspondence to Adviye Ergul. AKH and JSJ contribute equally to writing the evidence-based sections and drafting of this review.

DR was responsible for critical revision and formatting. AE participated in all aspects and areas of this review. Open Access This article is published under license to BioMed Central Ltd.

Reprints and permissions. Johansen, J. et al. Oxidative stress and the use of antioxidants in diabetes: Linking basic science to clinical practice. Cardiovasc Diabetol 4 , 5 Download citation. Received : 09 March Accepted : 29 April Published : 29 April Anyone you share the following link with will be able to read this content:.

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Search all BMC articles Search. Download PDF. Download ePub. Abstract Cardiovascular complications, characterized by endothelial dysfunction and accelerated atherosclerosis, are the leading cause of morbidity and mortality associated with diabetes.

Introduction It is a well-established fact that diabetes is a risk factor for cardiovascular disease [ 1 , 2 ]. What is oxidative stress? Figure 1. Full size image. Figure 2. References Pyorala K, Laakso M, Uusitupa M: Diabetes and atherosclerosis: an epidemiologic view.

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Article CAS PubMed Google Scholar Oberg BP, McMenamin E, Lucas FL, McMonagle E, Morrow J, Ikizler TA, Himmelfarb J: Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease.

Article PubMed Google Scholar Guzik TJ, West NE, Black E, McDonald D, Ratnatunga C, Pillai R, Channon KM: Vascular superoxide production by NAD P H oxidase: association with endothelial dysfunction and clinical risk factors.

Article CAS PubMed Google Scholar Guzik TJ, Mussa S, Gastaldi D, Sadowski J, Ratnatunga C, Pillai R, Channon KM: Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD P H oxidase and endothelial nitric oxide synthase.

Article CAS PubMed Google Scholar Ceriello A, Mercuri F, Quagliaro L, Assaloni R, Motz E, Tonutti L, Taboga C: Detection of nitrotyrosine in the diabetic plasma: evidence of oxidative stress.

Article CAS PubMed Google Scholar Aliciguzel Y, Ozen I, Aslan M, Karayalcin U: Activities of xanthine oxidoreductase and antioxidant enzymes in different tissues of diabetic rats. Article CAS PubMed Google Scholar Kitada M, Koya D, Sugimoto T, Isono M, Araki S, Kashiwagi A, Haneda M: Translocation of glomerular p47phox and p67phox by protein kinase C-beta activation is required for oxidative stress in diabetic nephropathy.

Article CAS PubMed Google Scholar Etoh T, Inoguchi T, Kakimoto M, Sonoda N, Kobayashi K, Kuroda J, Sumimoto H, Nawata H: Increased expression of NAD P H oxidase subunits, NOX4 and p22phox, in the kidney of streptozotocin-induced diabetic rats and its reversibity by interventive insulin treatment.

Article CAS PubMed Google Scholar Ergul A, Schultz Johansen J, Stromhaug C, Harris AK, Hutchinson J, Tawfik A, Rahimi A, Rhim E, Wells B, Caldwell RW: Vascular dysfunction of venous bypass conduits is mediated by reactive oxygen species in diabetes: Role of endothelin Article CAS PubMed Google Scholar Green K, Brand MD, Murphy MP: Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes.

Article CAS PubMed Google Scholar Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP: Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Article CAS PubMed Google Scholar Brownlee M: Biochemistry and molecular cell biology of diabetic complications.

Article CAS PubMed Google Scholar Kaul N, Siveski-Iliskovic N, Hill M, Khaper N, Seneviratne C, Singal PK: Probucol treatment reverses antioxidant and functional deficit in diabetic cardiomyopathy.

Article PubMed Google Scholar Hayden MR, Tyagi SC: Myocardial redox stress and remodeling in metabolic syndrome, type 2 diabetes mellitus, and congestive heart failure.

CAS PubMed Google Scholar Linke A, Adams V, Schulze PC, Erbs S, Gielen S, Fiehn E, Mobius-Winkler S, Schubert A, Schuler G, Hambrecht R: Antioxidative effects of exercise training in patients with chronic heart failure: increase in radical scavenger enzyme activity in skeletal muscle. Article CAS PubMed Google Scholar Cristina Polidori M, Pratico D, Savino K, Rokach J, Stahl W, Mecocci P: Increased F2 isoprostane plasma levels in patients with congestive heart failure are correlated with antioxidant status and disease severity.

Article PubMed Google Scholar Hensley K, Robinson KA, Gabbita SP, Salsman S, Floyd RA: Reactive oxygen species, cell signaling, and cell injury. Article CAS PubMed Google Scholar Hensley K, Benaksas EJ, Bolli R, Comp P, Grammas P, Hamdheydari L, Mou S, Pye QN, Stoddard MF, Wallis G: New perspectives on vitamin E: gamma-tocopherol and carboxyelthylhydroxychroman metabolites in biology and medicine.

Article CAS PubMed Google Scholar Hodgson JM, Watts GF, Playford DA, Burke V, Croft KD: Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes.

Article CAS PubMed Google Scholar Hodgson JM, Watts GF: Can coenzyme Q10 improve vascular function and blood pressure? Article CAS PubMed Google Scholar Watts GF, Playford DA, Croft KD, Ward NC, Mori TA, Burke V: Coenzyme Q 10 improves endothelial dysfunction of the brachial artery in Type II diabetes mellitus.

Article CAS PubMed Google Scholar Heller R, Unbehaun A, Schellenberg B, Mayer B, Werner-Felmayer G, Werner ER: L-ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterin. Article CAS PubMed Google Scholar Mekinova D, Chorvathova V, Volkovova K, Staruchova M, Grancicova E, Klvanoca J, Ondreicka R: Effect of intake of exogenous vitamins C, E and beta-carotene on the antioxidative status in kidneys of rats with streptozotocin-induced diabetes.

Article CAS PubMed Google Scholar Kedziora-kornatowska K, Szram S, Kornatowski T, Szadujkis-Szadurski L, Kedziora J, Bartosz G: Effect of vitamin E and vitamin C supplementation of antioxidative state and renal glomerular basement membrane thickness in diabetic kidney. Article Google Scholar Cinar M, Ulker S, Alper G, Evinc A: Effect of dietary vitamin E supplementation on vascular reactivity of thoracic aorta in streptozotocin-diabetic rats.

Article CAS PubMed Google Scholar Obrosova I, Fathallah L, Greene D: Early changes in lipid peroxidation and antioxidative defense in rat retina. Article CAS Google Scholar Kocak G, Aktan F, Canbolat O, Ozogul C, Elberg S, Yildizoglu-Ari N, Karasu C: Alpha-lipoic acid treatment ameliorates metabolic parameters, blood pressure, vascular reavtivity and morphology of vessels already damaged by streptozotocin-diabetes.

CAS Google Scholar Rauscher F, Sanders R, Watkins JI: Effects of coenzyme Q10 treatment on antioxidant pathways in normal and streptozotocin-induced diabetic rats. Article CAS PubMed Google Scholar Maritim A, Sanders R, Watkins JI: Effects of alpha-lipoic acid on biomarkers of oxidative stress in streptozotic-induced diabetic rats.

Article CAS PubMed Google Scholar Brands MW, Bell TD, Gibson B: Nitric oxide may prevent hypertension early in diabetes by counteracting renal actions of superoxide.

Article CAS PubMed Google Scholar Skyrme-Jones RA, O'Brien RC, Berry KL, Meredith IT: Vitamin E supplementation improves endothelial function in type I diabetes mellitus: a randomized, placebo-controlled study.

Article CAS PubMed Google Scholar Beckman JA, Goldfine AB, Gordon MB, Garrett LA, Keaney JF, Creager MA: Oral antioxidant therapy improves endothelial function in Type 1 but not Type 2 diabetes mellitus. CAS Google Scholar Gaede P, Poulsen HE, Parving HH, Pedersen O: Double-blind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in Type 2 diabetic patients.

Article CAS PubMed Google Scholar Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P: Vitamin E supplementation and cardiovascular events in high-risk patients. Article CAS PubMed Google Scholar Boaz M, Smetana S, Weinstein T, Matas Z, Gafter U, Iaina A, Knecht A, Weissgarten Y, Brunner D, Fainaru M: Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease SPACE : randomised placebo-controlled trial.

Article CAS PubMed Google Scholar Gaede P, Vedel P, Larsen N, Jensen GVH, Parving H-H, Pedersen O: Multifactorial intervention and cardiovascular disease in patients with Type 2 diabetes.

Article PubMed Google Scholar Sacco M, Pellegrini F, Roncaglioni MC, Avanzini F, Tognoni G, Nicolucci A: Primary prevention of cardiovascular events with low-dose aspirin and Vitamin E in Type 2 diabetic patients: Results of the Primary Prevention Project PPP trial.

Article CAS PubMed Google Scholar Lonn EM, Yusuf S, Dzavik V, Doris CI, Yi Q, Smith S, Moore-Cox A, Bosch J, Riley WA, Teo KK: Effects of ramipril and vitamin E on atherosclerosis : The study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E SECURE.

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Antioxidant supplements for diabetes management Liver cleanse cleanse language of interest to view the total gor in your shpplements language. Oxidants fiabetes Antioxidants in Medical Science received citations as per google scholar report. Lij Zou, Department of Chemistry, University of Dongguan, Dongguan, China, Email: Liou qq. Received: Aug, Manuscript No. EJMOAMS- ; Editor assigned: Aug, Pre QC No. EJMOAMS- PQ ; Reviewed: Aug, QC No. EJMOAMS- ; Revised: Aug, Manuscript No. There is no doubt that diet plays a key role Citrus bioflavonoids and blood circulation the Antioxidant supplements for diabetes management and treatment Antioxidxnt diabetes. In addition to Antioixdant medications, it is important to follow a Signs of blood sugar crashes diet managemfnt keep your blood Antioxidannt level in control. If your diet lacks adequate nutrition, adding dietary supplements might be recommended. Here is a quick guide on the use of vitamin, mineral and antioxidant supplements for diabetes. Vitamins play a key role in glucose metabolism and the lack of these nutrients could make supplementation necessary to manage and prevent diabetes-related complications. Due to abnormal glucose metabolism in diabetics, there is an excess production of free radicals.