The Role of Antioxidant Micronutrients in the Prevention of Diabetic Complications

Bonnefont-Rousselot D, Bastard JP, Jaudon MC, et al. Consequences of the diabetic status on the oxidant/antioxidant balance. Diabetes Metab 2000; 26: 163–76 Maritim AC, Sanders RA, Watkins III JB. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Molecular Toxicology 2003; 17: 193–7 Wierusz-Wysocka B, Wysocki H, Byks H, et al. Metabolic control quality and free radical activity in diabetic patients. Diabetes Res Clin Pract 1995; 27: 193–7 Suzuki YJ, Forman HJ, Sevenian A. Oxidants as stimulators of signal transduction. Free Radic Biol Med 1997; 22: 269–85 Bonnefont-Rousselot D. Glucose and reactive oxygen species. Curr Opin Clin Nutr Metab Care 2002; 5: 561–8 Opara EC, Abdel-Rahman E, Soliman S, et al. Depletion of total antioxidant capacity in type 2 diabetes. Metabolism 1999; 48: 1414–7 Jakus V. The role of free radicals, oxidative stress and antioxidant systems in diabetic vascular disease. Bratisl Lek Listy 2000; 101: 541–51 Bonnefont-Rousselot D. Antioxidant and anti-AGE therapeutics: evaluation and perspectives [in French]. J Soc Biol 2001; 195: 391–8 Armstrong AM, Chesnutt JE, Gormley MJ. The effect of dietary treatment on lipid peroxidation and antioxidant status in newly diagnosed noninsulin dependent diabetes. Free Radic Biol Med 1996; 21: 719–26 The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977–86 Cunningham JJ. Micronutrients as nutriceutical interventions in diabetes mellitus. J Am Coll Nutr 1998; 17: 7–10 Food and Nutrition Board, National Research Council. Recommended dietary allowances. 10th ed. Washington, DC: Nat Acad Press, 1989 Anderson RA. Chromium, glucose intolerance and diabetes. J Am Coll Nutr 1998; 17: 548–55 Salgueiro MJ, Krebs N, Zubillaga MB, et al. Zinc and diabetes mellitus: is there a need of zinc supplementation in diabetes mellitus patients? Biol Trace Elem Res 2001; 81: 215–28 O’Connell BS. Select vitamins and minerals in the management of diabetes. Diabetes Spectrum 2001; 14: 133–48 Franz MJ, Bantle JP, Beebe CA, et al. Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. Diabetes Care 2002; 25: 148–98 Opara EC. Oxidative stress, micronutrients, diabetes mellitus and its complications. J R Soc Health 2002; 122: 28–34 Poucheret P, Verma S, Grynpas MD, et al. Vanadium and diabetes. Mol Cell Biol 1998; 188: 73–80 Cam MC, Brownsey RW, McNeil JH. Mechanisms of vanadium action: insulin mimetic or insulin-enhancing agent? Can J Physiol Pharmacol 2000; 78:829–47 Hamel FG, Duckworth WC. The relationship between insulin and vanadium metabolism in insulin target tissues. Mol Cell Biochem 1995; 153: 95–102 Verma S, Cam C. Nutritional factors that can favorably influence the glucose/insulin system: vanadium. J Am Coll Nutr 1998; 17: 11–8 Sakurai H. A new concept: the use of vanadium complexes in the treatment of diabetes mellitus. Chem Res 2002; 2: 237–48 Thompson KH, McNeill JH. Effect of vanadyl sulfate feeding on susceptibility to peroxidative damage in diabetic rats. Res Commun Chem Path Pharmacol 1993; 80: 187–200 Cam MC, Peterson A, Brownsey RW, et al. Long-term effectiveness of oral vanadyl sulphate in streptozotocin-diabetic rats. Diabetologia 1993; 36: 218–24 Thompson KH, Leichter J, McNeill JH. Studies of vanadyl sulfate as a glucose-lowering agent in STZ-diabetic rats. Biochem Biophys Res Commun 1993; 197: 1549–55 Oster MH, Llobet JM, Domingo JL, et al. Vanadium treatment of diabetic Sprague-Dawley rats results in tissue vanadium accumulation and prooxidant effects. Toxicology 1993; 83: 115–30 Lapenna D, Ciofani G, Bruno C, et al. Vanadyl as a catalyst of human lipoprotein oxidation. Biochem Pharmacol 2002; 63: 375–80 Goldfine A, Simonson D, Folli F, et al. Metabolic effects of sodium metavanadate in humans with insulin-dependent and non-insulin-dependent diabetes mellitus: in vivo and in vitro studies. J Clin Endocrinol Metab 1995; 80: 3311–20 Cohen N, Halberstam M, Shlimovich P, et al. Oral vanadyl sulfate improves hepatic and peripheral insulin sensitivity in patients with non-insulin dependent diabetes mellitus. J Clin Invest 1995; 95: 2501–9 Halberstam M, Cohen N, Shlimovich P, et al. Oral vanadyl sulfate improves insulin sensitivity in NIDDM but not obese nondiabetic subjects. Diabetes 1996; 45: 659–66 Boden G, Chen X, Ruiz J, et al. Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with non-insulin dependent diabetes mellitus. Metabolism 1996; 45: 1130–5 Harland BF, Harden-Williams BA. Is vanadium of nutritional importance yet? J Am Diet Assoc 1994; 94: 891–4 Thompson KH, Liboiron BD, Sun Y,et al. Preparation and characterization of vanadyl complexes with bidentate maltol-type ligands: in vivo comparisons of anti-diabetic therapeutic potential. J Biol Inorg Chem 2003; 8: 66–74 McNeill JH, Yuen VG, Dai S, et al. Increased potency of vanadium using organic ligands. Mol Cell Biochem 1995; 153: 175–80 McCarty MF. Homologous physiological effects of phenformin and chromium picolinate. Med Hypotheses 1993; 41: 316–24 Mertz W. Interaction of chromium with insulin: a progress report. Nutr Rev 1998; 56: 174–7 Morris B, Macneil S, Hardisty CA, et al. Chromium homeostasis in patients with type II (NIDDM) diabetes. J Trace Elem Exp Med 1999; 13: 57–61 Anderson RA, Cheng N, Bryden NA, et al. Beneficial effects of chromium for people with diabetes. Diabetes 1997; 46: 1786–91 Ravina A, Slezak L, Rubal A, et al. Clinical use of trace element chromium (III) in the treatment of diabetes mellitus. J Trace Elem Exp Med 1995; 8: 183–90 Ravina A, Slezak L, Mirsky N, et al. Reversal of corticosteroid-induced diabetes with supplemental chromium. Diabet Med 1999; 16: 164–7 Cefalu WT, Bell-Farrow AD, Stegner J, et al. Effect of chromium picolinate on insulin sensitivity in vivo. J Trace Elem Exp Med 1999; 12: 71–83 Jovanovic L, Gutierrez M, Peterson CM. Chromium supplementation for women with gestational diabetes mellitus. J Trace Elem Exp Med 1999; 12: 91–7 Cheng N, Zhu X, Shi H, et al. Follow-up survey of people in China with type 2 diabetes mellitus consuming supplemental chromium. J Trace Elem Exp Med 1999; 12: 55–60 Sherman L, Glennon JA, Brech WJ, et al. Failure of trivalent chromium to improve hyperglycemia in diabetes mellitus. Metabolism 1968; 17: 439–42 Anderson RA, Polansky MM, Bryden NA, et al. Effects of supplemental chromium on patients with symptoms of reactive hypoglycemia. Metabolism 1987; 36: 351–5 Abraham AS, Brooks BA, Eylat U. The effect of chromium supplementation on serum glucose and lipids in patients with non-insulin-dependent diabetes mellitus. Metab Clin Exp 1992; 41: 768–71 Trow LG, Lewis J, Greenwood RH, et al. Lack of effect of dietary chromium supplementation on glucose tolerance, plasma insulin and lipoprotein levels in patients with type 2 diabetes. Int J Vitam Nutr Res 2000; 70: 14–8 Uusitupa MI, Mykkanen L, Siitonen O, et al. Chromium supplementation in impaired glucose tolerance of elderly: effects on blood glucose, plasma insulin, C-peptide and lipid levels. Br J Nutr 1992; 68: 209–16 Lee NA, Reasner CA. Beneficial effect of chromium supplementation on serum triglycerides in NIDDM. Diabetes Care 1994; 17: 1449–52 Preuss HG, Anderson RA. Chromium uptake: examining recent literature 1997–1998. Curr Opin Clin Nutr Metab Care 1998; 1: 509–12 Garfinkel L, Garfinkel D. Magnesium regulation of the glycolytic pathway and the enzymes involved. Magnesium 1985; 4: 60–72 Durlach J, Bara M, editors. Le magnésium en biologie et en médecine. In: Technique et documentation, editions médicales internationales. 2ème éd. Paris: Cachan, 2000 Sjogren A, Floren CH, Nilsson A. Magnesium deficiency in IDDM related to level of glycosylated hemoglobin in diabetes. Diabetes 1986; 35: 459–63 American Diabetes Association. Magnesium supplementation in the treatment of diabetes (consensus treatment). Diabetes Care 1992; 15: 1065–7 De Valk HW, Stuyvenberg A, van Rijn HJM, et al. Plasma magnesium in patients with type 2 (non-insulin dependent) diabetes and non-diabetics attending an outpatient clinic for internal medicine. Clin Chem Enzyme Comm 1993; 5: 151–5 Mooradian AD, Failla M, Hoogwerf B, et al. Selected vitamins and minerals in diabetes. Diabetes Care 1994; 17: 464–79 Eibl NL, Kopp HP, Nowak HR, et al. Hypomagnesemia in type II diabetes: effect of a 3-month replacement therapy. Diabetes Care 1995; 18: 188–92 De Valk H. Magnesium in diabetes mellitus. J Med 1999; 54: 139–46 Lima DLM, Cruz T, Pousada JC, et al. The effect of magnesium supplementation in increasing doses on the control of type 2 diabetes. Diabetes Care 1998; 21: 682–6 Elamin A, Tuvemo T. Magnesium and insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 1990; 10: 203–9 Paolisso G, Sgambato S, Pizza G, et al. Improved insulin response and action by chronic magnesium administration in aged NIDDM subjects. Diabetes Care 1989; 121: 265–9 Gullestad L, Jacobsen T, Dolva LO. Effect of magnesium treatment on glycemic control and metabolic parameters in NIDDM patients. Diabetes Care 1994; 17: 460–1 De Valk HW, Verkaaik R, van Rijn HJ, et al. Oral magnesium supplementation in insulin-requiring type 2 patients. Diabet Med 1998; 15: 503–7 Resnick LM, Gupta RK, Bhargava KK, et al. Cellular ions in hypertension, diabetes, and obesity: a nuclear magnetic resonance spectroscopic study. Hypertension 1991; 17: 951–7 Barbagallo M, Gupta R, Dominguez LJ, et al. Cellular ionic alteration with aging: relation to hypertension and diabetes. J Am Soc Geriatrics 2000; 48: 1111–6 Paolisso G, Sgambato S, Passariello N, et al. Insulin induces opposite changes in plasma and erythrocyte magnesium concentration in normal man. Diabetologia 1986; 29: 644–7 Paolisso G, Scheen A, Cozzolino D, et al. Changes in glucose turnover parameters and improvement of glucose oxidation after 4-week magnesium administration in elderly noninsulin-dependent (type 2) diabetic patients. J Clin Endocrinol Metab 1994; 78: 1510–4 Guerrero-Romero F, Rodríguez-Morán M. Low serum magnesium levels and metabolic syndrome. Acta Diabetol 2002; 39: 209–13 Barbagallo M, Dominguez LJ, Galioto A, et al. Role of magnesium in insulin action, diabetes and cardio-metabolic syndrome X. Mol Aspects Med 2003; 24: 39–52 Kao WHL, Folsom AR, Nieto FJ, et al. Serum and dietary magnesium and the risk of type 2 diabetes mellitus: the Atherosclerosis Risk in Communities (ARIC) Study. Arch Intern Med 1999; 159: 2151–9 Corsonello A, Lentile R, Buemi M, et al. Serum ionized magnesium levels in type 2 diabetic patients with microalbuminuria or clinical proteinuria. Am J Nephrol 2000; 20: 187–92 Walter RM, Uriu-Hare JY, Olin KL, et al. Copper, zinc, manganese, and magnesium status and complications of diabetes mellitus. Diabetes Care 1991; 14: 1050–6 Sjogren A, Floren CH, Nilsson A. Magnesium, potassium and zinc deficiency in subjects with type II diabetes mellitus. Acta Med Scand 1988; 224: 461–6 Faure P, Roussel A, Coudray C, et al. Zinc and insulin sensitivity. Biol Trace Elem Res 1992; 32: 305–10 Blostein-Fujii A, DiSilvestro RA, Frid D, et al. Short-term zinc supplementation in women with non-insulin-dependent diabetes mellitus: effects on plasma 5′- nucleotidase activities, insulin-like growth factor I concentration, and lipoprotein oxidation rates in vitro. Am J Clin Nutr 1997; 66: 639–42 Halliwell B, Gutteridge JMC, editors. Free radicals in biology and medicine. 3rd ed. New York: Oxford University Press, 1999 Raz I, Havini E. Trace elements in blood cells of diabetic subjects. Diabetes Res 1989; 10: 21–4 Faure P, Benhamou PY, Perard A, et al. Lipid peroxidation in insulin-dependent diabetic patients with early retina degenerative lesions: effects of an oral zinc supplementation. Eur J Clin Nutr 1995; 49: 282–8 Song MK, Rosenthal MJ, Naliboff BD, et al. Effects of bovine prostate powder on zinc, glucose, and insulin metabolism in old patients with non-insulin-dependent diabetes mellitus. Metabolism 1998; 47: 39–43 Ruiz C, Alegria A, Barbera R, et al. Selenium, zinc and copper in plasma of patients with type 1 diabetes mellitus in different metabolic states. J Trace Elem Med Biol 1998; 12: 91–5 Navarro-Alarcon M, Lopez-G de la Serrana H, Perez-Valero V, et al. Serum and urine selenium concentrations as indicators of body status in patients with diabetes mellitus. Sci Total Environ 1999; 228: 79–85 Battell ML, Delgatty HL, McNeill JH. Sodium selenate corrects glucose tolerance and heart function in STZ diabetic rats. Mol Cell Biochem 1998; 179: 27–34 Douillet C, Bost M, Accominotti M, et al. Effects of selenium and vitamin E supplements on tissue lipids, peroxides, and fatty acid distribution in experimental diabetes. Lipids 1998; 33: 393–9 Bartfay WJ, Hou D, Brittenham GM, et al. The synergistic effect of vitamin E and selenium in iron-overloaded mouse hearts. Can J Cardiol 1998; 14: 937–41 Chaudière J, Ferrari-Iliou R. Intracellular antioxidants: from chemical to biochemical mechanisms. Food Chem Toxicol 1999; 37: 949–62 Saari JT. Implication of nonenzymatic glycosylation as a mode of damage in dietary copper deficiency. Nutr Res 1994; 14: 1689–99 Saari JT. Evidence that dimethylsulfoxide inhibits defects of copper deficiency by inhibition of glycation. Nutr Res 1996; 16: 467–77 Cunningham J, Leffell M, Mearkle P, et al. Elevated plasma ceruloplasmin in insulin-dependent diabetes mellitus: evidence for increased oxidative stress as a variable complication. Metabolism 1995; 44: 996–9 Miller GD, Keen CL, Sterns JS, et al. Copper deficiency and arachidonic acid enhance insulin secretion in isolated pancreatic islets from lean (FaFa) Zucker rats. Pancreas 1998; 17: 390–6 Sitasawad S, Deshpande M, Katdare M, et al. Beneficial effect of supplementation with copper sulfate on STZ-diabetic mice (IDDM). Diabetes Res Clin 2001; 52: 77–84 Macmillan-Crow LA, Cruthirds DL. Invited review: manganese Superoxide dismutase in disease. Free Radic Res 2001; 34: 325–36 Thompson KH, Godin DV, Lee M. Tissue antioxidant status in streptozotocin-induced diabetes in rats: effects of dietary manganese deficiency. Biol Trace Elem Res 1992; 35: 213–24 Ekmekcioglu C, Prohaska C, Pomazal K, et al. Concentrations of seven trace elements in different hematological matrices in patients with type 2 diabetes as compared to healthy controls. Biol Trace Elem Res 2001; 79: 205–19 Polidori MC, Mecocci P, Stahl W, et al. Plasma levels of lipophilic antioxidants in very old patients with type 2 diabetes. Diabetes Metab Res Rev 2000; 16: 15–9 Salonen JT, Nyyssonen K, Tuomainen TP, et al. Increased risk of non-insulin-dependent diabetes mellitus at low plasma vitamin E concentrations: a four-year follow-up study in men. Br Med J 1995; 311: 1124–7 Ihara Y, Toyokuni S, Uchida K, et al. Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes. Diabetes 1999; 48: 927–32 Ihara Y, Yamada Y, Toyokuni S, et al. Antioxidant alpha-tocopherol ameliorates glycemic control of GK rats, a model of type 2 diabetes. FEBS Lett 2000; 473: 24–6 Bursell SE, King GL. Can protein kinase C inhibition and vitamin E prevent the development of diabetic vascular complications? Diabetes Res Clin Pract 1999; 45: 169–82 Paolisso G, D’Amore A, Giugliano D, et al. Pharmacological doses of vitamin E improve insulin action in healthy subjects and non-insulin dependent diabetic patients. Am J Clin Nutr 1993; 57: 650–6 Paolisso G, D’Amore A, Galzerano D, et al. Daily vitamin E supplements improve metabolic control but not insulin secretion in elderly type 2 diabetic patients. Diabetes Care 1993; 16: 1433–7 Ceriello A, Giugliano D, Quataro A, et al. Vitamin E reduction of protein glycosylation in diabetes. Diabetes Care 1991; 14: 68–72 Jain SK, McVie R, Jaramillo JJ, et al. Effect of modest vitamin E supplementation on blood glycated hemoglobin and triglyceride levels and red cell indices in type 1 diabetic patients. J Am Coll Nutr 1996; 15: 458–61 Manzella D, Barbieri M, Ragno E, et al. Chronic administration of pharmacologic doses of vitamin E improves the cardiac autonomie nervous system in patients with type 2 diabetes. Am J Clin Nutr 2001; 73: 1052–7 Reaven PD, Herold DA, Barnett J, et al. Effects of vitamin E on susceptibility of low-density lipoprotein and low-density lipoprotein subfractions to oxidation and on protein glycation in NIDDM. Diabetes Care 1995; 18: 807–16 Gomez-Perez FJ, Valles-Sanchez VE, Lopez-Alvarenga JC, et al. Vitamin E modifies neither fructosamine nor HbA1c levels in poorly controlled diabetes. Rev Invest Clin 1996; 48: 421–4 Skrha J, Sindelka G, Kvasnicka J, et al. Insulin action and fibrinolysis influenced by vitamin E in obese type 2 diabetes mellitus. Diab Res Clin Pract 1999; 4: 27–33 Tutuncu NB, Bayraktar N, Varli K. Reversal of defective nerve conduction with vitamin E supplementation in type 2 diabetes. Diabetes Care 1998; 21: 1915–8 Neslihan BT, Bayraktar M, Varli K. Reversal of defective nerve conduction with vitamin E supplementation in type 2 diabetes. Diabetes Care 1998; 21: 1915–8 Bursell SE, Clermont AC, Aiello LP, et al. High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes. Diabetes Care 1999; 22: 1245–51 Upritchard JE, Sutherland WHF, Mann JI. Effect of supplementation with tomato juice, vitamin E, and vitamin C on LDL oxidation and products of inflammatory activity in type 2 diabetes. Diabetes Care 2000; 23: 733–8 Devaraj S, Jiala I. Low-density lipoprotein postsecretory modification, monocyte function, and circulating adhesion molecules in type 2 diabetic patients with and without macrovascular complications: the effect of alpha-tocopherol supplementation. Circulation 2000; 2: 191–6 Skyrme-Jones RA, Meredith IT. Soluble adhesion molecules, endothelial function and vitamin E in type 1 diabetes. Coron Artery Dis 2001; 12: 69–75 Andrew R, Skyrme-Jones P, O’Brien RC, et al. Vitamin E supplementation improves endothelial function in type 1 diabetes mellitus: a randomized, placebo-controlled study. J Am Coll Cardiol 2000; 36: 94–102 Devaraj S, Cabo Chan AV, Jialal I. α-Tocopherol supplementation decreases plasminogen activator inhibitor-1 and P-selectin levels in type 2 diabetic patients. Diabetes Care 2002; 25: 524–9 Astley S, Langrish-Smith A, Southon S, et al. Vitamin E supplementation and oxidative damage to DNA and plasma LDL in type 1 diabetes. Diabetes Care 1999; 22: 1626–31 Pinkney JH, Downs L, Hopton M, et al. Endothelial dysfunction in type 1 diabetes mellitus: relationship with LDL oxidation and the effects of vitamin E. Diabet Med 1999; 16: 993–9 Paolisso G, Giugliano D. Oxidative stress and insulin action: is there a relationship? Diabetologia 1996; 39: 357–63 Sharma A, Kharb S, Chugh SN, et al. Evaluation of oxidative stress before and after control of glycemia and after vitamin E supplementation in diabetic patients. Metabolism 2000; 49: 160–2 Bendich A, Machlin J. Safety of oral intake of vitamin E. Am J Clin Nutr 1988; 48: 612–9 Stephens NG, Parsons A, Schofield PM, et al. Randomized, controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study. Lancet 1996; 347: 781–6 Jain SK. Should high-dose vitamin E supplementation be recommended to diabetic patients? Diabetes Care 1999; 22: 1242–4 Meydani SN, Meydani M, Blumberg JB, et al. Assessment of safety of supplementation with different amounts of vitamin E in healthy older adults. Am J Clin Nutr 1998; 68: 311–8 Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supplementation and cardiovascular events in high-risk patients: the Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342: 154–60 Lonn E, Yusuf S, Hoogwerf B, et al. Effects of vitamin E on cardiovascular and microvascular outcomes in high-risk patients with diabetes: results of the HOPE study and MICRO-HOPE substudy. Diabetes Care 2002; 25: 1919–27 Steinberg D. Clinical trials of antioxidants in atherosclerosis: are we doing the right thing? Lancet 1995; 346: 36–8 Mayer-Davis EJ, Costacou T, King I, et al. Plasma and dietary vitamin E in relation to incidence of type 2 diabetes: the Insulin Resistance and Atherosclerosis Study (IRAS). Diabetes Care 2002; 25: 2172–7 McDonnell MG, Archbold GP. Plasma ubiquinol/cholesterol ratios in patients with hyperlipidemia, those with diabetes mellitus and in patients requiring dialysis. Clin Chim Acata 1996; 253: 117–23 Wittenstein B, Klein M, Finckh B, et al. Plasma antioxidants in pediatric patients with glycogen storage disease, diabetes mellitus, and hypercholesterolemia. Free Radie Biol Med 2002; 33: 103–10 Hodgson JM, Watts GF, Playford DA,et al. Coenzyme Q(10) improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr 2002; 56: 1137–42 Watts GF, Palyford DA, Croft KD, et al. Coenzyme Q(10) improves endothelial dysfunction in the brachial artery in type II diabetes mellitus. Diabetologia 2002; 45: 420–6 Kagan VE, Serbinova EA, Forte T, et al. Recycling of vitamin E in human low density lipoproteins. J Lipid Res 1992; 33: 385–97 Will JC, Ford ES, Bowman BA. Serum vitamin C concentrations and diabetes: findings from the third National Health and Nutrition Examination Survey, 1988–1994. Am J Clin Nutr 1999; 70: 49–52 Cunningham JJ, Mearkle PL, Brown RG. Vitamin C: an aldose reductase inhibitor that normalizes erythrocyte sorbitol in insulin-dependent diabetes mellitus. J Am Coll Nutr 1994; 13: 344–50 Ting HH, Timimi FK, Boles KS, et al. Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 1996; 97: 22–8 Timimi FK, Ting HH, Haley EA, et al. Vitamin C improves endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. J Am Coll Cardiol 1998; 31: 552–7 Craven PA, De Rubertis FR, Kagan VE, et al. Effects of a supplementation with vitamin C or E on albuminuria, glomerular TGF-beta, and glomerular size in diabetes. J Am Soc Nephrol 1997; 8: 1405–14 Gaede P, Poulsen HE, Parving HH, et al. Double-blind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in type 2 diabetic patients. Diabet Med 2001; 18: 756–60 Gale EAM. Nicotinamide: potential for the prevention of type 1 diabetes? Horm Metab Res 1996; 28: 361–4 Greensbaum CJ, Kahn SE, Palmer JP. Nicotinamide effects on glucose metabolism in subjects at risk for IDDM. Diabetes 1996; 45: 1631–4 Elliott RB, Pilcher CC, Fergusson DM, et al. A population-based strategy to prevent insulin-dependent diabetes using nicotinamide. J Pediatr Endocrinol Metab 1996; 9: 501–9 Lampeter EF, Klinghammer A, Scherbaum WA, et al. The Deutsch Nicotinamide Intervention Study: an attempt to prevent type 1 diabetes. Diabetes 1998; 47: 980–4 Pozzilli P, Vissali N, Girhlanda G, et al. Nicotinamide increases C-peptide secretion in patients with recent onset type 1 diabetes. Diabet Med 1989; 6: 568–72 Pozzilli P, Vissali N, Signore A, et al. Double-blind trial of nicotinamide in recent onset IDDM (the IMDIAB III study). Diabetologia 1995; 38: 848–52 Pozzilli P, Browne PD, Kolb H. The Nicotinamide Trialists: meta-analysis of nicotinamide treatment in patients with recent-onset IDDM. Diabetes Care 1996; 19: 1357–63 Polo V, Saibene A, Pontiroli AE. Nicotinamide improves insulin secretion and metabolic control in lean type 2 patients with secondary failure to sulphonylureas. Acta Diabetol 1998; 35: 61–4 Vissali N, Cavallo MG, Signore A, et al. A multi-center, randomized trial of two different doses of nicotinamide in patients with recent-onset type 1 diabetes (the IMDIAB VI). Diabetes Metab Res Rev 1999; 15: 181–5 Behme MT. Nicotinamide and diabetes prevention. Nutr Rev 1995; 53: 137–9 Kolb H, Burkart V. Nicotinamide in type 1 diabetes mechanism of action revisited. Diabetes Care 1999; 22Suppl. 2: B16–20 Knip M, Douek IF, Moore WPT, et al. Safety of high-dose nicotinamide: a review. Diabetologia 2000; 43: 1337–45 Cole HS, Lopez R, Cooperman JM. Riboflavin deficiency in children with diabetes mellitus. Acta Diabetol Lat 1976; 13: 25–9 Lenti G, Lombardi A, Pagano G. Prophylactic and therapeutic use of vitamins in diabetes. Acta Vitaminol Enzymol 1980; 2: 67–74 Welch GN, Loscalizo J. Homocysteine and atherothrombosis. New Engl J Med 1998; 338: 1042–50 Bar-On H, Kidron M, Friedlander Y, et al. Plasma total homocysteine levels in subjects with hyperinsulinemia. J Int Med 2000; 247: 287–94 Aarsand AK, Carlsen SM. Folate administration reduces circulating homocystein levels in NIDDM patients on long-term metformin treatment. J Intern Med 1998; 244: 169–74 Baliga BS, Reynolds T, Fink LM, et al. Hyperhomocysteinemia in type 2 diabetes mellitus: cardiovascular risk factors and effect of treatment with folic acid and pyridoxine. Endocrinol Pract 2000; 6: 435–41 Chait A, Malinow MR, Nevin DN, et al. Increased dietary micronutrients decrease serum homocystein concentrations in patients at high risk of cardiovascular disease. Am J Clin Nutr 1999; 70: 881–7 Suzuki YJ, Tsuchiya M, Packer L. Thioctic acid and dihydrolipoic acid are novel antioxidants which interact with reactive oxygen species. Free Radic Res Commun 1991; 15: 255–63 Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001; 17: 888–95 Han D, Handelman G, Marcocci L, et al. Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. Biofactors 1997; 6: 321–38 Jain SK, McVie R. Effect of glycemic control, race (white versus black) and duration of diabetes on reduced glutathione content in erythrocytes of diabetic patients. Metabolism 1994; 43: 306–9 Konrad D, Somwar R, Sweeney G, et al. The antihyperglycemic drug olipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation. Diabetes 2001; 50: 1464–71 Jacob S, Ruus P, Herman R, et al. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type 2 diabetes mellitus: a placebo-controlled pilot trial. Free Radie Biol Med 1999; 27: 309–14 Nagamatsu M, Nickander KK, Schmelzer JD, et al. Lipoic acid improves nerve blood flow, reduces oxidative stress and improves diabetic neuropathy. Diabetes Care 1995; 18: 1160–7 Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic peripheral neuropathy with the antioxidant alpha-lipoic acid: a 3-week multicentre randomized controlled trial (ALADIN Study). Diabetologia 1995; 38: 1425–33 Ziegler D, Schatz H, Conrad F, et al. Effects of treatment with the antioxidant α-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. Diabetes Care 1997; 20: 369–73 Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized trial (ALADIN III Study). ALADIN III Study Group: alpha-lipoic acid in diabetic neuropathy. Diabetes Care 1999; 22: 1296–301 Ziegler D, Reljanovid M, Mehnert H, et al. Alpha-lipoic acid in the treatment of diabetic polyneuropathy in Germany: current evidence from clinical trials. Exp Clin Endocrin Diabet 1999; 107: 421–30 Diabetes and Nutrition Study Group (DNSG) of the European Association for the Study of Diabetes (EASDF). Recommendations for the nutritional management of patients with diabetes mellitus. Diabetes Nutr Metab 1995; 8: 186–9 Vertommen J, van den Enden M, Simoens L, et al. Flavonoid treatment reduces glycation and lipid peroxidation in experimental diabetic rats. Phytother Res 1994; 8: 430–2 Lean ME, Noroozu M, Kelly I, et al. Dietary flavonols protect diabetic human lymphocytes against oxidative damage to DNA. Diabetes 1999; 48: 176–81 Al-Abed Y, Mitsuhashi T, Li HW, et al. Inhibition of advanced glycation endproduct formation by acetaldehyde: role in the cardioprotective effect of ethanol. Proc Natl Acad Sci U S A 1999; 96: 2385–90