Treatments in Endocrinology

, Volume 3, Issue 1, pp 41–52

The Role of Antioxidant Micronutrients in the Prevention of Diabetic Complications

Review Article

Abstract

Diabetes mellitus is associated with an increased production of reactive oxygen species and a reduction in antioxidant defenses. This leads to oxidative stress, which is partly responsible for diabetic complications. Tight glycemic control is the most effective way of preventing or decreasing these complications. Nevertheless, antioxidant micronutrients can be proposed as adjunctive therapy in patients with diabetes. Indeed, some minerals and vitamins are able to indirectly participate in the reduction of oxidative stress in diabetic patients by improving glycemic control and/or are able to exert antioxidant activity.

This article reviews the use of minerals (vanadium, chromium, magnesium, zinc, selenium, copper) and vitamins or cofactors (tocopherol [vitamin E], ascorbic acid [vitamin C], ubidecarenone [ubiquinone; coenzyme Q], nicotinamide, riboflavin, thioctic acid [lipoic acid], flavonoids) in diabetes, with a particular focus on the prevention of diabetic complications. Results show that dietary supplementation with micronutrients may be a complement to classical therapies for preventing and treating diabetic complications. Supplementation is expected to be more effective when a deficiency in these micronutrients exists. Nevertheless, many clinical studies have reported beneficial effects in individuals without deficiencies, although several of these studies were short term and had small sample sizes. However, a randomized, double-blind, placebo-controlled, multicenter trial showed that thioctic acid at an oral dosage of 800 mg/day for 4 months significantly improved cardiac autonomic neuropathy in type 2 diabetic patients. Above all, individuals with diabetes should be educated about the importance of consuming adequate amounts of vitamins and minerals from natural food sources, within the constraints of recommended sugar and carbohydrate intake.

References

  1. 1.
    Bonnefont-Rousselot D, Bastard JP, Jaudon MC, et al. Consequences of the diabetic status on the oxidant/antioxidant balance. Diabetes Metab 2000; 26: 163–76PubMedGoogle Scholar
  2. 2.
    Maritim AC, Sanders RA, Watkins III JB. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Molecular Toxicology 2003; 17: 193–7CrossRefGoogle Scholar
  3. 3.
    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: 193–7PubMedCrossRefGoogle Scholar
  4. 4.
    Suzuki YJ, Forman HJ, Sevenian A. Oxidants as stimulators of signal transduction. Free Radic Biol Med 1997; 22: 269–85PubMedCrossRefGoogle Scholar
  5. 5.
    Bonnefont-Rousselot D. Glucose and reactive oxygen species. Curr Opin Clin Nutr Metab Care 2002; 5: 561–8PubMedCrossRefGoogle Scholar
  6. 6.
    Opara EC, Abdel-Rahman E, Soliman S, et al. Depletion of total antioxidant capacity in type 2 diabetes. Metabolism 1999; 48: 1414–7PubMedCrossRefGoogle Scholar
  7. 7.
    Jakus V. The role of free radicals, oxidative stress and antioxidant systems in diabetic vascular disease. Bratisl Lek Listy 2000; 101: 541–51PubMedGoogle Scholar
  8. 8.
    Bonnefont-Rousselot D. Antioxidant and anti-AGE therapeutics: evaluation and perspectives [in French]. J Soc Biol 2001; 195: 391–8PubMedGoogle Scholar
  9. 9.
    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: 719–26PubMedCrossRefGoogle Scholar
  10. 10.
    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: 977–86CrossRefGoogle Scholar
  11. 11.
    Cunningham JJ. Micronutrients as nutriceutical interventions in diabetes mellitus. J Am Coll Nutr 1998; 17: 7–10PubMedGoogle Scholar
  12. 12.
    Food and Nutrition Board, National Research Council. Recommended dietary allowances. 10th ed. Washington, DC: Nat Acad Press, 1989Google Scholar
  13. 13.
    Anderson RA. Chromium, glucose intolerance and diabetes. J Am Coll Nutr 1998; 17: 548–55PubMedGoogle Scholar
  14. 14.
    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: 215–28PubMedCrossRefGoogle Scholar
  15. 15.
    O’Connell BS. Select vitamins and minerals in the management of diabetes. Diabetes Spectrum 2001; 14: 133–48CrossRefGoogle Scholar
  16. 16.
    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: 148–98PubMedCrossRefGoogle Scholar
  17. 17.
    Opara EC. Oxidative stress, micronutrients, diabetes mellitus and its complications. J R Soc Health 2002; 122: 28–34CrossRefGoogle Scholar
  18. 18.
    Poucheret P, Verma S, Grynpas MD, et al. Vanadium and diabetes. Mol Cell Biol 1998; 188: 73–80Google Scholar
  19. 19.
    Cam MC, Brownsey RW, McNeil JH. Mechanisms of vanadium action: insulin mimetic or insulin-enhancing agent? Can J Physiol Pharmacol 2000; 78:829–47PubMedCrossRefGoogle Scholar
  20. 20.
    Hamel FG, Duckworth WC. The relationship between insulin and vanadium metabolism in insulin target tissues. Mol Cell Biochem 1995; 153: 95–102PubMedCrossRefGoogle Scholar
  21. 21.
    Verma S, Cam C. Nutritional factors that can favorably influence the glucose/insulin system: vanadium. J Am Coll Nutr 1998; 17: 11–8PubMedGoogle Scholar
  22. 22.
    Sakurai H. A new concept: the use of vanadium complexes in the treatment of diabetes mellitus. Chem Res 2002; 2: 237–48Google Scholar
  23. 23.
    Thompson KH, McNeill JH. Effect of vanadyl sulfate feeding on susceptibility to peroxidative damage in diabetic rats. Res Commun Chem Path Pharmacol 1993; 80: 187–200Google Scholar
  24. 24.
    Cam MC, Peterson A, Brownsey RW, et al. Long-term effectiveness of oral vanadyl sulphate in streptozotocin-diabetic rats. Diabetologia 1993; 36: 218–24PubMedCrossRefGoogle Scholar
  25. 25.
    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: 1549–55PubMedCrossRefGoogle Scholar
  26. 26.
    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: 115–30PubMedCrossRefGoogle Scholar
  27. 27.
    Lapenna D, Ciofani G, Bruno C, et al. Vanadyl as a catalyst of human lipoprotein oxidation. Biochem Pharmacol 2002; 63: 375–80PubMedCrossRefGoogle Scholar
  28. 28.
    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: 3311–20PubMedCrossRefGoogle Scholar
  29. 29.
    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: 2501–9PubMedCrossRefGoogle Scholar
  30. 30.
    Halberstam M, Cohen N, Shlimovich P, et al. Oral vanadyl sulfate improves insulin sensitivity in NIDDM but not obese nondiabetic subjects. Diabetes 1996; 45: 659–66PubMedCrossRefGoogle Scholar
  31. 31.
    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: 1130–5PubMedCrossRefGoogle Scholar
  32. 32.
    Harland BF, Harden-Williams BA. Is vanadium of nutritional importance yet? J Am Diet Assoc 1994; 94: 891–4PubMedCrossRefGoogle Scholar
  33. 33.
    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: 66–74PubMedCrossRefGoogle Scholar
  34. 34.
    McNeill JH, Yuen VG, Dai S, et al. Increased potency of vanadium using organic ligands. Mol Cell Biochem 1995; 153: 175–80PubMedCrossRefGoogle Scholar
  35. 35.
    McCarty MF. Homologous physiological effects of phenformin and chromium picolinate. Med Hypotheses 1993; 41: 316–24PubMedCrossRefGoogle Scholar
  36. 36.
    Mertz W. Interaction of chromium with insulin: a progress report. Nutr Rev 1998; 56: 174–7PubMedCrossRefGoogle Scholar
  37. 37.
    Morris B, Macneil S, Hardisty CA, et al. Chromium homeostasis in patients with type II (NIDDM) diabetes. J Trace Elem Exp Med 1999; 13: 57–61Google Scholar
  38. 38.
    Anderson RA, Cheng N, Bryden NA, et al. Beneficial effects of chromium for people with diabetes. Diabetes 1997; 46: 1786–91PubMedCrossRefGoogle Scholar
  39. 39.
    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: 183–90Google Scholar
  40. 40.
    Ravina A, Slezak L, Mirsky N, et al. Reversal of corticosteroid-induced diabetes with supplemental chromium. Diabet Med 1999; 16: 164–7PubMedCrossRefGoogle Scholar
  41. 41.
    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: 71–83CrossRefGoogle Scholar
  42. 42.
    Jovanovic L, Gutierrez M, Peterson CM. Chromium supplementation for women with gestational diabetes mellitus. J Trace Elem Exp Med 1999; 12: 91–7CrossRefGoogle Scholar
  43. 43.
    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: 55–60CrossRefGoogle Scholar
  44. 44.
    Sherman L, Glennon JA, Brech WJ, et al. Failure of trivalent chromium to improve hyperglycemia in diabetes mellitus. Metabolism 1968; 17: 439–42PubMedCrossRefGoogle Scholar
  45. 45.
    Anderson RA, Polansky MM, Bryden NA, et al. Effects of supplemental chromium on patients with symptoms of reactive hypoglycemia. Metabolism 1987; 36: 351–5PubMedCrossRefGoogle Scholar
  46. 46.
    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: 768–71PubMedCrossRefGoogle Scholar
  47. 47.
    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: 14–8PubMedCrossRefGoogle Scholar
  48. 48.
    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: 209–16PubMedCrossRefGoogle Scholar
  49. 49.
    Lee NA, Reasner CA. Beneficial effect of chromium supplementation on serum triglycerides in NIDDM. Diabetes Care 1994; 17: 1449–52PubMedCrossRefGoogle Scholar
  50. 50.
    Preuss HG, Anderson RA. Chromium uptake: examining recent literature 1997–1998. Curr Opin Clin Nutr Metab Care 1998; 1: 509–12PubMedCrossRefGoogle Scholar
  51. 51.
    Garfinkel L, Garfinkel D. Magnesium regulation of the glycolytic pathway and the enzymes involved. Magnesium 1985; 4: 60–72PubMedGoogle Scholar
  52. 52.
    Durlach J, Bara M, editors. Le magnésium en biologie et en médecine. In: Technique et documentation, editions médicales internationales. 2ème éd. Paris: Cachan, 2000Google Scholar
  53. 53.
    Sjogren A, Floren CH, Nilsson A. Magnesium deficiency in IDDM related to level of glycosylated hemoglobin in diabetes. Diabetes 1986; 35: 459–63PubMedCrossRefGoogle Scholar
  54. 54.
    American Diabetes Association. Magnesium supplementation in the treatment of diabetes (consensus treatment). Diabetes Care 1992; 15: 1065–7Google Scholar
  55. 55.
    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: 151–5Google Scholar
  56. 56.
    Mooradian AD, Failla M, Hoogwerf B, et al. Selected vitamins and minerals in diabetes. Diabetes Care 1994; 17: 464–79PubMedGoogle Scholar
  57. 57.
    Eibl NL, Kopp HP, Nowak HR, et al. Hypomagnesemia in type II diabetes: effect of a 3-month replacement therapy. Diabetes Care 1995; 18: 188–92PubMedCrossRefGoogle Scholar
  58. 58.
    De Valk H. Magnesium in diabetes mellitus. J Med 1999; 54: 139–46Google Scholar
  59. 59.
    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: 682–6CrossRefGoogle Scholar
  60. 60.
    Elamin A, Tuvemo T. Magnesium and insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 1990; 10: 203–9PubMedCrossRefGoogle Scholar
  61. 61.
    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: 265–9CrossRefGoogle Scholar
  62. 62.
    Gullestad L, Jacobsen T, Dolva LO. Effect of magnesium treatment on glycemic control and metabolic parameters in NIDDM patients. Diabetes Care 1994; 17: 460–1PubMedGoogle Scholar
  63. 63.
    De Valk HW, Verkaaik R, van Rijn HJ, et al. Oral magnesium supplementation in insulin-requiring type 2 patients. Diabet Med 1998; 15: 503–7PubMedCrossRefGoogle Scholar
  64. 64.
    Resnick LM, Gupta RK, Bhargava KK, et al. Cellular ions in hypertension, diabetes, and obesity: a nuclear magnetic resonance spectroscopic study. Hypertension 1991; 17: 951–7PubMedCrossRefGoogle Scholar
  65. 65.
    Barbagallo M, Gupta R, Dominguez LJ, et al. Cellular ionic alteration with aging: relation to hypertension and diabetes. J Am Soc Geriatrics 2000; 48: 1111–6Google Scholar
  66. 66.
    Paolisso G, Sgambato S, Passariello N, et al. Insulin induces opposite changes in plasma and erythrocyte magnesium concentration in normal man. Diabetologia 1986; 29: 644–7PubMedCrossRefGoogle Scholar
  67. 67.
    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: 1510–4PubMedCrossRefGoogle Scholar
  68. 68.
    Guerrero-Romero F, Rodríguez-Morán M. Low serum magnesium levels and metabolic syndrome. Acta Diabetol 2002; 39: 209–13PubMedCrossRefGoogle Scholar
  69. 69.
    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: 39–52PubMedCrossRefGoogle Scholar
  70. 70.
    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: 2151–9PubMedCrossRefGoogle Scholar
  71. 71.
    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: 187–92PubMedCrossRefGoogle Scholar
  72. 72.
    Walter RM, Uriu-Hare JY, Olin KL, et al. Copper, zinc, manganese, and magnesium status and complications of diabetes mellitus. Diabetes Care 1991; 14: 1050–6PubMedCrossRefGoogle Scholar
  73. 73.
    Sjogren A, Floren CH, Nilsson A. Magnesium, potassium and zinc deficiency in subjects with type II diabetes mellitus. Acta Med Scand 1988; 224: 461–6PubMedCrossRefGoogle Scholar
  74. 74.
    Faure P, Roussel A, Coudray C, et al. Zinc and insulin sensitivity. Biol Trace Elem Res 1992; 32: 305–10PubMedCrossRefGoogle Scholar
  75. 75.
    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: 639–42PubMedGoogle Scholar
  76. 76.
    Halliwell B, Gutteridge JMC, editors. Free radicals in biology and medicine. 3rd ed. New York: Oxford University Press, 1999Google Scholar
  77. 77.
    Raz I, Havini E. Trace elements in blood cells of diabetic subjects. Diabetes Res 1989; 10: 21–4PubMedGoogle Scholar
  78. 78.
    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: 282–8PubMedGoogle Scholar
  79. 79.
    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: 39–43PubMedCrossRefGoogle Scholar
  80. 80.
    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: 91–5PubMedCrossRefGoogle Scholar
  81. 81.
    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: 79–85PubMedCrossRefGoogle Scholar
  82. 82.
    Battell ML, Delgatty HL, McNeill JH. Sodium selenate corrects glucose tolerance and heart function in STZ diabetic rats. Mol Cell Biochem 1998; 179: 27–34PubMedCrossRefGoogle Scholar
  83. 83.
    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: 393–9PubMedCrossRefGoogle Scholar
  84. 84.
    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: 937–41PubMedGoogle Scholar
  85. 85.
    Chaudière J, Ferrari-Iliou R. Intracellular antioxidants: from chemical to biochemical mechanisms. Food Chem Toxicol 1999; 37: 949–62PubMedCrossRefGoogle Scholar
  86. 86.
    Saari JT. Implication of nonenzymatic glycosylation as a mode of damage in dietary copper deficiency. Nutr Res 1994; 14: 1689–99CrossRefGoogle Scholar
  87. 87.
    Saari JT. Evidence that dimethylsulfoxide inhibits defects of copper deficiency by inhibition of glycation. Nutr Res 1996; 16: 467–77CrossRefGoogle Scholar
  88. 88.
    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: 996–9PubMedCrossRefGoogle Scholar
  89. 89.
    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: 390–6PubMedCrossRefGoogle Scholar
  90. 90.
    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: 77–84CrossRefGoogle Scholar
  91. 91.
    Macmillan-Crow LA, Cruthirds DL. Invited review: manganese Superoxide dismutase in disease. Free Radic Res 2001; 34: 325–36PubMedCrossRefGoogle Scholar
  92. 92.
    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: 213–24PubMedCrossRefGoogle Scholar
  93. 93.
    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: 205–19PubMedCrossRefGoogle Scholar
  94. 94.
    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: 15–9PubMedCrossRefGoogle Scholar
  95. 95.
    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: 1124–7CrossRefGoogle Scholar
  96. 96.
    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: 927–32PubMedCrossRefGoogle Scholar
  97. 97.
    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: 24–6PubMedCrossRefGoogle Scholar
  98. 98.
    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: 169–82PubMedCrossRefGoogle Scholar
  99. 99.
    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: 650–6PubMedGoogle Scholar
  100. 100.
    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: 1433–7PubMedCrossRefGoogle Scholar
  101. 101.
    Ceriello A, Giugliano D, Quataro A, et al. Vitamin E reduction of protein glycosylation in diabetes. Diabetes Care 1991; 14: 68–72PubMedCrossRefGoogle Scholar
  102. 102.
    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: 458–61PubMedGoogle Scholar
  103. 103.
    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: 1052–7PubMedGoogle Scholar
  104. 104.
    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: 807–16PubMedCrossRefGoogle Scholar
  105. 105.
    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: 421–4PubMedGoogle Scholar
  106. 106.
    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: 27–33CrossRefGoogle Scholar
  107. 107.
    Tutuncu NB, Bayraktar N, Varli K. Reversal of defective nerve conduction with vitamin E supplementation in type 2 diabetes. Diabetes Care 1998; 21: 1915–8PubMedCrossRefGoogle Scholar
  108. 108.
    Neslihan BT, Bayraktar M, Varli K. Reversal of defective nerve conduction with vitamin E supplementation in type 2 diabetes. Diabetes Care 1998; 21: 1915–8CrossRefGoogle Scholar
  109. 109.
    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: 1245–51PubMedCrossRefGoogle Scholar
  110. 110.
    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: 733–8PubMedCrossRefGoogle Scholar
  111. 111.
    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: 191–6CrossRefGoogle Scholar
  112. 112.
    Skyrme-Jones RA, Meredith IT. Soluble adhesion molecules, endothelial function and vitamin E in type 1 diabetes. Coron Artery Dis 2001; 12: 69–75PubMedCrossRefGoogle Scholar
  113. 113.
    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: 94–102CrossRefGoogle Scholar
  114. 114.
    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: 524–9PubMedCrossRefGoogle Scholar
  115. 115.
    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: 1626–31PubMedCrossRefGoogle Scholar
  116. 116.
    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: 993–9PubMedCrossRefGoogle Scholar
  117. 117.
    Paolisso G, Giugliano D. Oxidative stress and insulin action: is there a relationship? Diabetologia 1996; 39: 357–63PubMedCrossRefGoogle Scholar
  118. 118.
    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: 160–2PubMedCrossRefGoogle Scholar
  119. 119.
    Bendich A, Machlin J. Safety of oral intake of vitamin E. Am J Clin Nutr 1988; 48: 612–9PubMedGoogle Scholar
  120. 120.
    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: 781–6PubMedCrossRefGoogle Scholar
  121. 121.
    Jain SK. Should high-dose vitamin E supplementation be recommended to diabetic patients? Diabetes Care 1999; 22: 1242–4PubMedCrossRefGoogle Scholar
  122. 122.
    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: 311–8PubMedGoogle Scholar
  123. 123.
    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: 154–60PubMedCrossRefGoogle Scholar
  124. 124.
    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: 1919–27PubMedCrossRefGoogle Scholar
  125. 125.
    Steinberg D. Clinical trials of antioxidants in atherosclerosis: are we doing the right thing? Lancet 1995; 346: 36–8PubMedCrossRefGoogle Scholar
  126. 126.
    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: 2172–7PubMedCrossRefGoogle Scholar
  127. 127.
    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: 117–23CrossRefGoogle Scholar
  128. 128.
    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: 103–10CrossRefGoogle Scholar
  129. 129.
    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: 1137–42PubMedCrossRefGoogle Scholar
  130. 130.
    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: 420–6PubMedCrossRefGoogle Scholar
  131. 131.
    Kagan VE, Serbinova EA, Forte T, et al. Recycling of vitamin E in human low density lipoproteins. J Lipid Res 1992; 33: 385–97PubMedGoogle Scholar
  132. 132.
    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: 49–52PubMedGoogle Scholar
  133. 133.
    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: 344–50PubMedGoogle Scholar
  134. 134.
    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: 22–8PubMedCrossRefGoogle Scholar
  135. 135.
    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: 552–7PubMedCrossRefGoogle Scholar
  136. 136.
    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: 1405–14PubMedGoogle Scholar
  137. 137.
    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: 756–60PubMedCrossRefGoogle Scholar
  138. 138.
    Gale EAM. Nicotinamide: potential for the prevention of type 1 diabetes? Horm Metab Res 1996; 28: 361–4PubMedCrossRefGoogle Scholar
  139. 139.
    Greensbaum CJ, Kahn SE, Palmer JP. Nicotinamide effects on glucose metabolism in subjects at risk for IDDM. Diabetes 1996; 45: 1631–4CrossRefGoogle Scholar
  140. 140.
    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: 501–9PubMedCrossRefGoogle Scholar
  141. 141.
    Lampeter EF, Klinghammer A, Scherbaum WA, et al. The Deutsch Nicotinamide Intervention Study: an attempt to prevent type 1 diabetes. Diabetes 1998; 47: 980–4PubMedCrossRefGoogle Scholar
  142. 142.
    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: 568–72PubMedCrossRefGoogle Scholar
  143. 143.
    Pozzilli P, Vissali N, Signore A, et al. Double-blind trial of nicotinamide in recent onset IDDM (the IMDIAB III study). Diabetologia 1995; 38: 848–52PubMedCrossRefGoogle Scholar
  144. 144.
    Pozzilli P, Browne PD, Kolb H. The Nicotinamide Trialists: meta-analysis of nicotinamide treatment in patients with recent-onset IDDM. Diabetes Care 1996; 19: 1357–63PubMedCrossRefGoogle Scholar
  145. 145.
    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: 61–4PubMedCrossRefGoogle Scholar
  146. 146.
    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: 181–5CrossRefGoogle Scholar
  147. 147.
    Behme MT. Nicotinamide and diabetes prevention. Nutr Rev 1995; 53: 137–9PubMedCrossRefGoogle Scholar
  148. 148.
    Kolb H, Burkart V. Nicotinamide in type 1 diabetes mechanism of action revisited. Diabetes Care 1999; 22Suppl. 2: B16–20PubMedGoogle Scholar
  149. 149.
    Knip M, Douek IF, Moore WPT, et al. Safety of high-dose nicotinamide: a review. Diabetologia 2000; 43: 1337–45PubMedCrossRefGoogle Scholar
  150. 150.
    Cole HS, Lopez R, Cooperman JM. Riboflavin deficiency in children with diabetes mellitus. Acta Diabetol Lat 1976; 13: 25–9PubMedCrossRefGoogle Scholar
  151. 151.
    Lenti G, Lombardi A, Pagano G. Prophylactic and therapeutic use of vitamins in diabetes. Acta Vitaminol Enzymol 1980; 2: 67–74PubMedGoogle Scholar
  152. 152.
    Welch GN, Loscalizo J. Homocysteine and atherothrombosis. New Engl J Med 1998; 338: 1042–50PubMedCrossRefGoogle Scholar
  153. 153.
    Bar-On H, Kidron M, Friedlander Y, et al. Plasma total homocysteine levels in subjects with hyperinsulinemia. J Int Med 2000; 247: 287–94CrossRefGoogle Scholar
  154. 154.
    Aarsand AK, Carlsen SM. Folate administration reduces circulating homocystein levels in NIDDM patients on long-term metformin treatment. J Intern Med 1998; 244: 169–74PubMedCrossRefGoogle Scholar
  155. 155.
    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: 435–41Google Scholar
  156. 156.
    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: 881–7PubMedGoogle Scholar
  157. 157.
    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: 255–63PubMedCrossRefGoogle Scholar
  158. 158.
    Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001; 17: 888–95PubMedCrossRefGoogle Scholar
  159. 159.
    Han D, Handelman G, Marcocci L, et al. Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. Biofactors 1997; 6: 321–38PubMedCrossRefGoogle Scholar
  160. 160.
    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: 306–9PubMedCrossRefGoogle Scholar
  161. 161.
    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: 1464–71PubMedCrossRefGoogle Scholar
  162. 162.
    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: 309–14CrossRefGoogle Scholar
  163. 163.
    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: 1160–7PubMedCrossRefGoogle Scholar
  164. 164.
    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: 1425–33PubMedCrossRefGoogle Scholar
  165. 165.
    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: 369–73PubMedCrossRefGoogle Scholar
  166. 166.
    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: 1296–301PubMedCrossRefGoogle Scholar
  167. 167.
    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: 421–30CrossRefGoogle Scholar
  168. 168.
    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: 186–9Google Scholar
  169. 169.
    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: 430–2CrossRefGoogle Scholar
  170. 170.
    Lean ME, Noroozu M, Kelly I, et al. Dietary flavonols protect diabetic human lymphocytes against oxidative damage to DNA. Diabetes 1999; 48: 176–81PubMedCrossRefGoogle Scholar
  171. 171.
    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: 2385–90PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Laboratoire de Biochimie Métabolique et Clinique (EA 3617), Faculté de PharmacieParisFrance
  2. 2.Laboratoire de Biochimie BHôpital de la Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP)ParisFrance
  3. 3.Laboratoire de Biochimie BHôpital de la SalpêtrièreParis Cedex 13France

Personalised recommendations