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The Role of Antioxidant Micronutrients in the Prevention of Diabetic Complications

  • Review Article
  • Published:
Treatments in Endocrinology

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.

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References

  1. Bonnefont-Rousselot D, Bastard JP, Jaudon MC, et al. Consequences of the diabetic status on the oxidant/antioxidant balance. Diabetes Metab 2000; 26: 163–76

    PubMed  CAS  Google Scholar 

  2. Maritim AC, Sanders RA, Watkins III JB. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Molecular Toxicology 2003; 17: 193–7

    Article  CAS  Google Scholar 

  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: 193–7

    Article  PubMed  CAS  Google Scholar 

  4. Suzuki YJ, Forman HJ, Sevenian A. Oxidants as stimulators of signal transduction. Free Radic Biol Med 1997; 22: 269–85

    Article  PubMed  CAS  Google Scholar 

  5. Bonnefont-Rousselot D. Glucose and reactive oxygen species. Curr Opin Clin Nutr Metab Care 2002; 5: 561–8

    Article  PubMed  CAS  Google Scholar 

  6. Opara EC, Abdel-Rahman E, Soliman S, et al. Depletion of total antioxidant capacity in type 2 diabetes. Metabolism 1999; 48: 1414–7

    Article  PubMed  CAS  Google Scholar 

  7. Jakus V. The role of free radicals, oxidative stress and antioxidant systems in diabetic vascular disease. Bratisl Lek Listy 2000; 101: 541–51

    PubMed  CAS  Google Scholar 

  8. Bonnefont-Rousselot D. Antioxidant and anti-AGE therapeutics: evaluation and perspectives [in French]. J Soc Biol 2001; 195: 391–8

    PubMed  CAS  Google Scholar 

  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: 719–26

    Article  PubMed  CAS  Google Scholar 

  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: 977–86

    Article  Google Scholar 

  11. Cunningham JJ. Micronutrients as nutriceutical interventions in diabetes mellitus. J Am Coll Nutr 1998; 17: 7–10

    PubMed  CAS  Google Scholar 

  12. Food and Nutrition Board, National Research Council. Recommended dietary allowances. 10th ed. Washington, DC: Nat Acad Press, 1989

    Google Scholar 

  13. Anderson RA. Chromium, glucose intolerance and diabetes. J Am Coll Nutr 1998; 17: 548–55

    PubMed  CAS  Google Scholar 

  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: 215–28

    Article  PubMed  CAS  Google Scholar 

  15. O’Connell BS. Select vitamins and minerals in the management of diabetes. Diabetes Spectrum 2001; 14: 133–48

    Article  Google Scholar 

  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: 148–98

    Article  PubMed  Google Scholar 

  17. Opara EC. Oxidative stress, micronutrients, diabetes mellitus and its complications. J R Soc Health 2002; 122: 28–34

    Article  CAS  Google Scholar 

  18. Poucheret P, Verma S, Grynpas MD, et al. Vanadium and diabetes. Mol Cell Biol 1998; 188: 73–80

    CAS  Google Scholar 

  19. Cam MC, Brownsey RW, McNeil JH. Mechanisms of vanadium action: insulin mimetic or insulin-enhancing agent? Can J Physiol Pharmacol 2000; 78:829–47

    Article  PubMed  CAS  Google Scholar 

  20. Hamel FG, Duckworth WC. The relationship between insulin and vanadium metabolism in insulin target tissues. Mol Cell Biochem 1995; 153: 95–102

    Article  PubMed  CAS  Google Scholar 

  21. Verma S, Cam C. Nutritional factors that can favorably influence the glucose/insulin system: vanadium. J Am Coll Nutr 1998; 17: 11–8

    PubMed  CAS  Google Scholar 

  22. Sakurai H. A new concept: the use of vanadium complexes in the treatment of diabetes mellitus. Chem Res 2002; 2: 237–48

    CAS  Google Scholar 

  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: 187–200

    CAS  Google Scholar 

  24. Cam MC, Peterson A, Brownsey RW, et al. Long-term effectiveness of oral vanadyl sulphate in streptozotocin-diabetic rats. Diabetologia 1993; 36: 218–24

    Article  PubMed  CAS  Google Scholar 

  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: 1549–55

    Article  PubMed  CAS  Google Scholar 

  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: 115–30

    Article  PubMed  CAS  Google Scholar 

  27. Lapenna D, Ciofani G, Bruno C, et al. Vanadyl as a catalyst of human lipoprotein oxidation. Biochem Pharmacol 2002; 63: 375–80

    Article  PubMed  CAS  Google Scholar 

  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: 3311–20

    Article  PubMed  CAS  Google Scholar 

  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: 2501–9

    Article  PubMed  CAS  Google Scholar 

  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: 659–66

    Article  PubMed  CAS  Google Scholar 

  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: 1130–5

    Article  PubMed  CAS  Google Scholar 

  32. Harland BF, Harden-Williams BA. Is vanadium of nutritional importance yet? J Am Diet Assoc 1994; 94: 891–4

    Article  PubMed  CAS  Google Scholar 

  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: 66–74

    Article  PubMed  CAS  Google Scholar 

  34. McNeill JH, Yuen VG, Dai S, et al. Increased potency of vanadium using organic ligands. Mol Cell Biochem 1995; 153: 175–80

    Article  PubMed  CAS  Google Scholar 

  35. McCarty MF. Homologous physiological effects of phenformin and chromium picolinate. Med Hypotheses 1993; 41: 316–24

    Article  PubMed  CAS  Google Scholar 

  36. Mertz W. Interaction of chromium with insulin: a progress report. Nutr Rev 1998; 56: 174–7

    Article  PubMed  CAS  Google Scholar 

  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: 57–61

    CAS  Google Scholar 

  38. Anderson RA, Cheng N, Bryden NA, et al. Beneficial effects of chromium for people with diabetes. Diabetes 1997; 46: 1786–91

    Article  PubMed  CAS  Google Scholar 

  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: 183–90

    CAS  Google Scholar 

  40. Ravina A, Slezak L, Mirsky N, et al. Reversal of corticosteroid-induced diabetes with supplemental chromium. Diabet Med 1999; 16: 164–7

    Article  PubMed  CAS  Google Scholar 

  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: 71–83

    Article  CAS  Google Scholar 

  42. Jovanovic L, Gutierrez M, Peterson CM. Chromium supplementation for women with gestational diabetes mellitus. J Trace Elem Exp Med 1999; 12: 91–7

    Article  CAS  Google Scholar 

  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: 55–60

    Article  Google Scholar 

  44. Sherman L, Glennon JA, Brech WJ, et al. Failure of trivalent chromium to improve hyperglycemia in diabetes mellitus. Metabolism 1968; 17: 439–42

    Article  PubMed  CAS  Google Scholar 

  45. Anderson RA, Polansky MM, Bryden NA, et al. Effects of supplemental chromium on patients with symptoms of reactive hypoglycemia. Metabolism 1987; 36: 351–5

    Article  PubMed  CAS  Google Scholar 

  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: 768–71

    Article  PubMed  CAS  Google Scholar 

  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: 14–8

    Article  PubMed  CAS  Google Scholar 

  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: 209–16

    Article  PubMed  CAS  Google Scholar 

  49. Lee NA, Reasner CA. Beneficial effect of chromium supplementation on serum triglycerides in NIDDM. Diabetes Care 1994; 17: 1449–52

    Article  PubMed  CAS  Google Scholar 

  50. Preuss HG, Anderson RA. Chromium uptake: examining recent literature 1997–1998. Curr Opin Clin Nutr Metab Care 1998; 1: 509–12

    Article  PubMed  CAS  Google Scholar 

  51. Garfinkel L, Garfinkel D. Magnesium regulation of the glycolytic pathway and the enzymes involved. Magnesium 1985; 4: 60–72

    PubMed  CAS  Google Scholar 

  52. Durlach J, Bara M, editors. Le magnésium en biologie et en médecine. In: Technique et documentation, editions médicales internationales. 2ème éd. Paris: Cachan, 2000

    Google Scholar 

  53. Sjogren A, Floren CH, Nilsson A. Magnesium deficiency in IDDM related to level of glycosylated hemoglobin in diabetes. Diabetes 1986; 35: 459–63

    Article  PubMed  CAS  Google Scholar 

  54. American Diabetes Association. Magnesium supplementation in the treatment of diabetes (consensus treatment). Diabetes Care 1992; 15: 1065–7

    Google Scholar 

  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: 151–5

    Google Scholar 

  56. Mooradian AD, Failla M, Hoogwerf B, et al. Selected vitamins and minerals in diabetes. Diabetes Care 1994; 17: 464–79

    PubMed  CAS  Google Scholar 

  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: 188–92

    Article  PubMed  CAS  Google Scholar 

  58. De Valk H. Magnesium in diabetes mellitus. J Med 1999; 54: 139–46

    Google Scholar 

  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: 682–6

    Article  Google Scholar 

  60. Elamin A, Tuvemo T. Magnesium and insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 1990; 10: 203–9

    Article  PubMed  CAS  Google Scholar 

  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: 265–9

    Article  Google Scholar 

  62. Gullestad L, Jacobsen T, Dolva LO. Effect of magnesium treatment on glycemic control and metabolic parameters in NIDDM patients. Diabetes Care 1994; 17: 460–1

    PubMed  CAS  Google Scholar 

  63. De Valk HW, Verkaaik R, van Rijn HJ, et al. Oral magnesium supplementation in insulin-requiring type 2 patients. Diabet Med 1998; 15: 503–7

    Article  PubMed  Google Scholar 

  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: 951–7

    Article  PubMed  CAS  Google Scholar 

  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: 1111–6

    CAS  Google Scholar 

  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: 644–7

    Article  PubMed  CAS  Google Scholar 

  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: 1510–4

    Article  PubMed  CAS  Google Scholar 

  68. Guerrero-Romero F, Rodríguez-Morán M. Low serum magnesium levels and metabolic syndrome. Acta Diabetol 2002; 39: 209–13

    Article  PubMed  CAS  Google Scholar 

  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: 39–52

    Article  PubMed  CAS  Google Scholar 

  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: 2151–9

    Article  PubMed  CAS  Google Scholar 

  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: 187–92

    Article  PubMed  CAS  Google Scholar 

  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: 1050–6

    Article  PubMed  Google Scholar 

  73. Sjogren A, Floren CH, Nilsson A. Magnesium, potassium and zinc deficiency in subjects with type II diabetes mellitus. Acta Med Scand 1988; 224: 461–6

    Article  PubMed  CAS  Google Scholar 

  74. Faure P, Roussel A, Coudray C, et al. Zinc and insulin sensitivity. Biol Trace Elem Res 1992; 32: 305–10

    Article  PubMed  CAS  Google Scholar 

  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: 639–42

    PubMed  CAS  Google Scholar 

  76. Halliwell B, Gutteridge JMC, editors. Free radicals in biology and medicine. 3rd ed. New York: Oxford University Press, 1999

  77. Raz I, Havini E. Trace elements in blood cells of diabetic subjects. Diabetes Res 1989; 10: 21–4

    PubMed  CAS  Google Scholar 

  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: 282–8

    PubMed  CAS  Google Scholar 

  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: 39–43

    Article  PubMed  CAS  Google Scholar 

  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: 91–5

    Article  PubMed  CAS  Google Scholar 

  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: 79–85

    Article  PubMed  CAS  Google Scholar 

  82. Battell ML, Delgatty HL, McNeill JH. Sodium selenate corrects glucose tolerance and heart function in STZ diabetic rats. Mol Cell Biochem 1998; 179: 27–34

    Article  PubMed  CAS  Google Scholar 

  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: 393–9

    Article  PubMed  CAS  Google Scholar 

  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: 937–41

    PubMed  CAS  Google Scholar 

  85. Chaudière J, Ferrari-Iliou R. Intracellular antioxidants: from chemical to biochemical mechanisms. Food Chem Toxicol 1999; 37: 949–62

    Article  PubMed  Google Scholar 

  86. Saari JT. Implication of nonenzymatic glycosylation as a mode of damage in dietary copper deficiency. Nutr Res 1994; 14: 1689–99

    Article  CAS  Google Scholar 

  87. Saari JT. Evidence that dimethylsulfoxide inhibits defects of copper deficiency by inhibition of glycation. Nutr Res 1996; 16: 467–77

    Article  CAS  Google Scholar 

  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: 996–9

    Article  PubMed  CAS  Google Scholar 

  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: 390–6

    Article  PubMed  CAS  Google Scholar 

  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: 77–84

    Article  CAS  Google Scholar 

  91. Macmillan-Crow LA, Cruthirds DL. Invited review: manganese Superoxide dismutase in disease. Free Radic Res 2001; 34: 325–36

    Article  PubMed  CAS  Google Scholar 

  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: 213–24

    Article  PubMed  CAS  Google Scholar 

  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: 205–19

    Article  PubMed  CAS  Google Scholar 

  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: 15–9

    Article  PubMed  CAS  Google Scholar 

  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: 1124–7

    Article  CAS  Google Scholar 

  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: 927–32

    Article  PubMed  CAS  Google Scholar 

  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: 24–6

    Article  PubMed  CAS  Google Scholar 

  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: 169–82

    Article  PubMed  CAS  Google Scholar 

  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: 650–6

    PubMed  CAS  Google Scholar 

  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: 1433–7

    Article  PubMed  CAS  Google Scholar 

  101. Ceriello A, Giugliano D, Quataro A, et al. Vitamin E reduction of protein glycosylation in diabetes. Diabetes Care 1991; 14: 68–72

    Article  PubMed  CAS  Google Scholar 

  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: 458–61

    PubMed  CAS  Google Scholar 

  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: 1052–7

    PubMed  CAS  Google Scholar 

  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: 807–16

    Article  PubMed  CAS  Google Scholar 

  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: 421–4

    PubMed  CAS  Google Scholar 

  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: 27–33

    Article  Google Scholar 

  107. Tutuncu NB, Bayraktar N, Varli K. Reversal of defective nerve conduction with vitamin E supplementation in type 2 diabetes. Diabetes Care 1998; 21: 1915–8

    Article  PubMed  CAS  Google Scholar 

  108. Neslihan BT, Bayraktar M, Varli K. Reversal of defective nerve conduction with vitamin E supplementation in type 2 diabetes. Diabetes Care 1998; 21: 1915–8

    Article  Google Scholar 

  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: 1245–51

    Article  PubMed  CAS  Google Scholar 

  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: 733–8

    Article  PubMed  CAS  Google Scholar 

  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: 191–6

    Article  Google Scholar 

  112. Skyrme-Jones RA, Meredith IT. Soluble adhesion molecules, endothelial function and vitamin E in type 1 diabetes. Coron Artery Dis 2001; 12: 69–75

    Article  PubMed  CAS  Google Scholar 

  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: 94–102

    Article  Google Scholar 

  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: 524–9

    Article  PubMed  CAS  Google Scholar 

  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: 1626–31

    Article  PubMed  CAS  Google Scholar 

  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: 993–9

    Article  PubMed  CAS  Google Scholar 

  117. Paolisso G, Giugliano D. Oxidative stress and insulin action: is there a relationship? Diabetologia 1996; 39: 357–63

    Article  PubMed  CAS  Google Scholar 

  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: 160–2

    Article  PubMed  CAS  Google Scholar 

  119. Bendich A, Machlin J. Safety of oral intake of vitamin E. Am J Clin Nutr 1988; 48: 612–9

    PubMed  CAS  Google Scholar 

  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: 781–6

    Article  PubMed  CAS  Google Scholar 

  121. Jain SK. Should high-dose vitamin E supplementation be recommended to diabetic patients? Diabetes Care 1999; 22: 1242–4

    Article  PubMed  CAS  Google Scholar 

  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: 311–8

    PubMed  CAS  Google Scholar 

  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: 154–60

    Article  PubMed  CAS  Google Scholar 

  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: 1919–27

    Article  PubMed  CAS  Google Scholar 

  125. Steinberg D. Clinical trials of antioxidants in atherosclerosis: are we doing the right thing? Lancet 1995; 346: 36–8

    Article  PubMed  CAS  Google Scholar 

  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: 2172–7

    Article  PubMed  CAS  Google Scholar 

  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: 117–23

    Article  CAS  Google Scholar 

  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: 103–10

    Article  CAS  Google Scholar 

  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: 1137–42

    Article  PubMed  CAS  Google Scholar 

  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: 420–6

    Article  PubMed  CAS  Google Scholar 

  131. Kagan VE, Serbinova EA, Forte T, et al. Recycling of vitamin E in human low density lipoproteins. J Lipid Res 1992; 33: 385–97

    PubMed  CAS  Google Scholar 

  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: 49–52

    PubMed  CAS  Google Scholar 

  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: 344–50

    PubMed  CAS  Google Scholar 

  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: 22–8

    Article  PubMed  CAS  Google Scholar 

  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: 552–7

    Article  PubMed  CAS  Google Scholar 

  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: 1405–14

    PubMed  CAS  Google Scholar 

  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: 756–60

    Article  PubMed  CAS  Google Scholar 

  138. Gale EAM. Nicotinamide: potential for the prevention of type 1 diabetes? Horm Metab Res 1996; 28: 361–4

    Article  PubMed  CAS  Google Scholar 

  139. Greensbaum CJ, Kahn SE, Palmer JP. Nicotinamide effects on glucose metabolism in subjects at risk for IDDM. Diabetes 1996; 45: 1631–4

    Article  Google Scholar 

  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: 501–9

    Article  PubMed  CAS  Google Scholar 

  141. Lampeter EF, Klinghammer A, Scherbaum WA, et al. The Deutsch Nicotinamide Intervention Study: an attempt to prevent type 1 diabetes. Diabetes 1998; 47: 980–4

    Article  PubMed  CAS  Google Scholar 

  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: 568–72

    Article  PubMed  CAS  Google Scholar 

  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: 848–52

    Article  PubMed  CAS  Google Scholar 

  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: 1357–63

    Article  PubMed  CAS  Google Scholar 

  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: 61–4

    Article  PubMed  CAS  Google Scholar 

  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: 181–5

    Article  Google Scholar 

  147. Behme MT. Nicotinamide and diabetes prevention. Nutr Rev 1995; 53: 137–9

    Article  PubMed  CAS  Google Scholar 

  148. Kolb H, Burkart V. Nicotinamide in type 1 diabetes mechanism of action revisited. Diabetes Care 1999; 22Suppl. 2: B16–20

    PubMed  Google Scholar 

  149. Knip M, Douek IF, Moore WPT, et al. Safety of high-dose nicotinamide: a review. Diabetologia 2000; 43: 1337–45

    Article  PubMed  CAS  Google Scholar 

  150. Cole HS, Lopez R, Cooperman JM. Riboflavin deficiency in children with diabetes mellitus. Acta Diabetol Lat 1976; 13: 25–9

    Article  PubMed  CAS  Google Scholar 

  151. Lenti G, Lombardi A, Pagano G. Prophylactic and therapeutic use of vitamins in diabetes. Acta Vitaminol Enzymol 1980; 2: 67–74

    PubMed  CAS  Google Scholar 

  152. Welch GN, Loscalizo J. Homocysteine and atherothrombosis. New Engl J Med 1998; 338: 1042–50

    Article  PubMed  CAS  Google Scholar 

  153. Bar-On H, Kidron M, Friedlander Y, et al. Plasma total homocysteine levels in subjects with hyperinsulinemia. J Int Med 2000; 247: 287–94

    Article  CAS  Google Scholar 

  154. Aarsand AK, Carlsen SM. Folate administration reduces circulating homocystein levels in NIDDM patients on long-term metformin treatment. J Intern Med 1998; 244: 169–74

    Article  PubMed  CAS  Google Scholar 

  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: 435–41

    CAS  Google Scholar 

  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: 881–7

    PubMed  CAS  Google Scholar 

  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: 255–63

    Article  PubMed  CAS  Google Scholar 

  158. Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001; 17: 888–95

    Article  PubMed  CAS  Google Scholar 

  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: 321–38

    Article  PubMed  CAS  Google Scholar 

  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: 306–9

    Article  PubMed  CAS  Google Scholar 

  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: 1464–71

    Article  PubMed  CAS  Google Scholar 

  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: 309–14

    Article  CAS  Google Scholar 

  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: 1160–7

    Article  PubMed  CAS  Google Scholar 

  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: 1425–33

    Article  PubMed  CAS  Google Scholar 

  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: 369–73

    Article  PubMed  CAS  Google Scholar 

  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: 1296–301

    Article  PubMed  CAS  Google Scholar 

  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: 421–30

    Article  CAS  Google Scholar 

  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: 186–9

    Google Scholar 

  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: 430–2

    Article  CAS  Google Scholar 

  170. Lean ME, Noroozu M, Kelly I, et al. Dietary flavonols protect diabetic human lymphocytes against oxidative damage to DNA. Diabetes 1999; 48: 176–81

    Article  PubMed  CAS  Google Scholar 

  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: 2385–90

    Article  PubMed  CAS  Google Scholar 

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Bonnefont-Rousselot, D. The Role of Antioxidant Micronutrients in the Prevention of Diabetic Complications. Mol Diag Ther 3, 41–52 (2004). https://doi.org/10.2165/00024677-200403010-00005

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