Diabetes and Oxidant Stress

  • Alicia J. Jenkins
  • Michael A. Hill
  • Kevin G. Rowley

Diabetes is associated with chronic micro- and macrovascular complications. Oxidative stress has been defined as ‘a “shift in the pro-oxidant – antioxidant balance in the pro-oxidant direction’.” Oxidant stress may initiate and exacerbate vascular (endothelial) damage through excess production of reactive oxygen species, depletion of nitric oxide, and damage to lipids, proteins, and DNA. Experimental results and theoretical constructs suggest oxidative stress is increased in diabetes, at least in some tissues, though not all studies are supportive. Potential markers of oxidation and glycoxidation are discussed. Pharmacological suppression of intracellular oxidative stress has prevented adverse biochemical and functional changes in cultured cells and animal models, and in some cases surrogate end-points of vascular damage in humans. Definitive clinical studies are awaited.


Diabetic Nephropathy Diabetic Subject Arterioscler Thromb Vasc Biol United Kingdom Prospective Diabetes Study Free Radic Biol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Amos AF, McCarty DJ, Zimmet P. The rising global burden of diabetes and its complications: estimates and projections to the year 2010. Diabetic Med 1997;14(Suppl 5): S1–S85.PubMedCrossRefGoogle Scholar
  2. 2.
    Mandrup-Poulsen T. Beta cell death and protection. Ann N Y Acad Sci 2003;1005:32–42.PubMedCrossRefGoogle Scholar
  3. 3.
    Kuroki T, Isshiki K, King GL. Oxidative stress: the lead or supporting actor in the pathogenesis of diabetic complications. J Am Soc Nephrol 2003;14(8 Suppl 3):S216–S220.PubMedCrossRefGoogle Scholar
  4. 4.
    Rosen P, Nawroth PP, King G, Moller W, Tritschler HJ, Packer L. The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes Metab Res Rev 2001;17(3):189–212.PubMedCrossRefGoogle Scholar
  5. 5.
    Ceriello A. New insights on oxidative stress and diabetic complications may lead to a “causal” antioxidant therapy. Diabetes Care 2003;26(5):1589–1596.PubMedCrossRefGoogle Scholar
  6. 6.
    American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2004;(Suppl 1):S5–S10.Google Scholar
  7. 7.
    American Diabetes Association Consensus Statement. Type 2 Diabetes in Children and Adolescents. Diabetes Care 2000;23:381–389.CrossRefGoogle Scholar
  8. 8.
    Despres JP, Lamarche B, Mauriege P, Cantin B, Dagenais GR, Moorjani S, Lupien PJ. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 1996;334(15):952–957.PubMedCrossRefGoogle Scholar
  9. 9.
    Uwaifo GI, Ratner RE. Diabetes 1996 Vital Statistics. American Diabetes Association.Google Scholar
  10. 10.
    Pickup JC, Williams G (Eds). Chronic complications of diabetes. Melbourne: Blackwell Press, 1994.Google Scholar
  11. 11.
    Pyorala K. Diabetes and heart disease. In: Mogensen CE, Standl E (Eds). Prevention and Treatment of the Diabetic Late Complications. New York: Walter de Gruyter 1989, pp. 151–168.Google Scholar
  12. 12.
    American Diabetes Association Position Statement. Diabetic nephropathy. Diabetes Care 2003;(Suppl 1):S94–S98.Google Scholar
  13. 13.
    Bloomgarden ZT. The epidemiology of complications. Diabetes Care 2002;25(5):924–932.PubMedCrossRefGoogle Scholar
  14. 14.
    Scott AR. Diabetic nephropathy. In: Donnelly R, Jonas J (Eds). Vascular Complications of Diabetes. Oxford: Blackwell Publishers, 2002, pp. 21–31.Google Scholar
  15. 15.
    American Diabetes Association Position Statement. Diabetic retinopathy. Diabetes Care 2003;(Suppl 1):S99–S102.Google Scholar
  16. 16.
    Borch-Johnsen K, Kreiner S. Proteinuria: value as a predictor of cardiovascular mortality in insulin dependent diabetes mellitus. Br Med J 1987;294:1651–1654.CrossRefGoogle Scholar
  17. 17.
    Bakis GL. Microalbuminuria: prognostic implications. Curr Opin Nephrol Hypertens 1996;5:219–223.CrossRefGoogle Scholar
  18. 18.
    Donahue RP, Orchard TJ. Diabetes mellitus and macrovascular complications. An epidemiological perspective. Diabetes Care 1992;15(9):1141–1155.Google Scholar
  19. 19.
    Collins R, Armitage J, Parish S, Sleigh P, Peto R, Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003;361(9374):2005–2016.Google Scholar
  20. 20.
    Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342(3): 145–153.Google Scholar
  21. 21.
    Herman WH, Alexander CM, Cook JR, Boccuzzi SJ, Musliner TA, Pedersen TR, Kjekshus J, Pyorala K. Effect of simvastatin treatment on cardiovascular resource utilization in impaired fasting glucose and diabetes. Findings from the Scandinavian Simvastatin Survival Study. Diabetes Care 1999;22(11):1771–1778.Google Scholar
  22. 22.
    Larsen J, Brekke M, Sandvik L, Arnesen H, Hanssen KF, Dahl-Jorgensen K. Silent coronary atheromatosis in type 1 diabetic patients and its relation to long-term glycemic control. Diabetes 2002;51(8):2637–2641.PubMedCrossRefGoogle Scholar
  23. 23.
    Penfornis A, Zimmermann C, Boumal D, Sabbah A, Meneveau N, Gaultier-Bourgeois S, Bassand JP, Bernard Y. Use of dobutamine stress echocardiography in detecting silent myocardial ischaemia in asymptomatic diabetic patients: a comparison with thallium scintigraphy and exercise testing. Diabet Med 2001;18(11):900–905.PubMedCrossRefGoogle Scholar
  24. 24.
    Arcavi L, Behar S, Caspi A, Reshef N, Boyko V, Knobler H. High fasting glucose levels as a predictor of worse clinical outcome in patients with coronary artery disease: results from the Bezafibrate Infarction Prevention (BIP) study. Am Heart J 2004;147(2):239–245.PubMedCrossRefGoogle Scholar
  25. 25.
    Tooke JE. Possible pathophysiological mechanisms for diabetic angiopathy in type 2 diabetes. J Diabetes Complicat 2000;14(4):197–200.PubMedCrossRefGoogle Scholar
  26. 26.
    Giardino I, Brownlee M. The biochemical basis of microvascular disease. In: Pickup JC, Williams G, (Eds). Textbook of Diabetes. Melbourne: Blackwell Press, 1997.Google Scholar
  27. 27.
    Klein R, Sharrett AR, Klein BE, Moss SE, Folsom AR, Wong TY, et al. The association of atherosclerosis, vascular risk factors, and retinopathy in adults with diabetes: the Atherosclerosis Risk in Communities study. Ophthalmology 2002;109(7):1225–1234.PubMedCrossRefGoogle Scholar
  28. 28.
    Jenkins AJ, Best JD, Klein RL, Lyons TJ. Lipoproteins, glycoxidation and diabetic angiopathy. Diabetes Metab Res Rev 2004;20(5):349–368.PubMedCrossRefGoogle Scholar
  29. 29.
    Shore AC, Tooke JE. Microvascular function and haemodynamic disturbances in diabetes mellitus and its complications. In: Pickup JC, Williams G (Eds). Textbook of Diabetes. Melbourne: Blackwell Press, 1997.Google Scholar
  30. 30.
    Diamond JR. Analogous pathobiologic mechanisms in glomerulosclerosis and atherosclerosis. Kidney Int 1991;31(Suppl):S29–S34.Google Scholar
  31. 31.
    Lyons TJ, Jenkins AJ. Glycation, oxidation, and lipoxidation in the development of the complications of diabetes: a carbonyl stress hypothesis. Diabetes Rev 1997;5:365–391.Google Scholar
  32. 32.
    Stitt AW, Jenkins AJ, Cooper ME. Advanced glycation end products and diabetic complications. Expert Opin Investig Drugs 2002;11(9):1205–1223.PubMedCrossRefGoogle Scholar
  33. 33.
    Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001;414(6865):813–820.PubMedCrossRefGoogle Scholar
  34. 34.
    Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000;404(6779): 787–790.PubMedCrossRefGoogle Scholar
  35. 35.
    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. New Engl J Med 1993;329:977–986.CrossRefGoogle Scholar
  36. 36.
    Nathan DM, Lachin J, Cleary P, Orchard T, Brillon DJ, Backlund JY, O’Leary DH, Genuth S, Diabetes Control and Complications Trial, Epidemiology of Diabetes Interventions and Complications Research Group. Intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes mellitus. N Engl J Med 2003;348(23):2294–2303.Google Scholar
  37. 37.
    UKPDS Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes UKPDS 33. Lancet 1998;352:837–853.CrossRefGoogle Scholar
  38. 38.
    Herman WH, Crofford OB. The relationship between metabolic control and complications. In: Pickup JC, Williams G, (Eds). Textbook of Diabetes. Melbourne: Blackwell Press, 1997.Google Scholar
  39. 39.
    Baynes JW, Thorpe SR. Oxidative stress in diabetes. In: Packer L, Rosen P, Tritschler HJ, King GL (Eds). Antioxidants in Diabetes Management. New York: Marcel Decker, 2000, pp. 77–91.Google Scholar
  40. 40.
    Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 1999;48(1):1–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Droge W. Free radicals in the physiological control of cell function. Physiol Rev 2002;82(1):47–95.PubMedGoogle Scholar
  42. 42.
    Rice Evans CA, Diplock AT, Symons MCR. Introduction to free radicals. Techniques in Free Radical Research. In: Burdon RH and, van Knippenberg PH (Eds). Laboratory Techniques in Biochemistry and Molecular Biology. Amsterdam: Elsevier, 1991, pp. 1–18.Google Scholar
  43. 43.
    Taniyama Y, Griendling KK. Reactive oxygen species in the vasculature: molecular and cellular mechanisms. Hypertension 2003;42(6):1075–1081.PubMedCrossRefGoogle Scholar
  44. 44.
    Ceriello A. New insights on oxidative stress and diabetic complications may lead to a “causal” antioxidant therapy. Diabetes Care 2003;26(5):1589–1596.PubMedCrossRefGoogle Scholar
  45. 45.
    Giugliano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care 1996;19(3):257–267.PubMedCrossRefGoogle Scholar
  46. 46.
    Farkas K, Sarman B, Jermendy G, Somogyi A. Endothelial nitric oxide in diabetes mellitus: too much or not enough? Diabetes Nutr Metab 2000;13(5):287–297.PubMedGoogle Scholar
  47. 47.
    Bonnefont-Rousselot D. Glucose and reactive oxygen species. Curr Opin Clin Nutr Metab Care 2002;5(5):561–568.PubMedCrossRefGoogle Scholar
  48. 48.
    Rosen P, Du X, Sui GZ. Molecular mechanisms of endothelial dysfunction in the diabetic heart. Adv Exp Med Biol 2001;498:75–86.PubMedGoogle Scholar
  49. 49.
    Piconi L, Quagliaro L, Ceriello A. Oxidative stress in diabetes. Clin Chem Lab Med 2003;41(9):1144–1149.PubMedCrossRefGoogle Scholar
  50. 50.
    Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 2000;87(10):840–844.PubMedGoogle Scholar
  51. 51.
    Garcia Soriano F, Virag L, Jagtap P, Szabo E, Mabley JG, Liaudet L, Marton A, Hoyt DG, Murthy KG, Salzman AL, Southan GJ, Szabo C. Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation. Nat Med 2001;7(1):108–113.PubMedCrossRefGoogle Scholar
  52. 52.
    Szabo C, Mabley JG, Moeller SM, Shimanovich R, Pacher P, Virag L, Soriano FG, Van Duzer JH, Williams W, Salzman AL, Groves JT. Part I: Pathogenetic role of peroxynitrite in the development of diabetes and diabetic vascular complications: studies with FP15, a novel potent peroxynitrite decomposition catalyst. Mol Med 2002;8(10):571–580.PubMedGoogle Scholar
  53. 53.
    Pacher P, Liaudet L, Soriano FG, Mabley JG, Szabo E, Szabo C. The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes. Diabetes 2002;51(2):514–521.PubMedCrossRefGoogle Scholar
  54. 54.
    Haj-Yehia AI, Nassar T, Assaf P, Nassar H, Anggard EE. Effects of the superoxide dismutase-mimic compound TEMPOL on oxidant stress-mediated endothelial dysfunction. Antioxid Redox Signal 1999;1(2):221–232.PubMedCrossRefGoogle Scholar
  55. 55.
    Nassar T, Kadery B, Lotan C, Da’as N, Kleinman Y, Haj-Yehia A. Effects of the superoxide dismutase-mimetic compound tempol on endothelial dysfunction in streptozotocin-induced diabetic rats. Eur J Pharmacol 2002;436(1–2):111–118.PubMedCrossRefGoogle Scholar
  56. 56.
    Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001;17(10):888–895.PubMedCrossRefGoogle Scholar
  57. 57.
    Vanella A, Russo A, Acquaviva R, Campisi A, Di Giacomo C, Sorrenti V, Barcellona ML. L-propionyl-carnitine as superoxide scavenger, antioxidant, and DNA cleavage protector. Cell Biol Toxicol 2000;16(2):99–104.PubMedCrossRefGoogle Scholar
  58. 58.
    Cotter MA, Jack AM, Cameron NE. Effects of the protein kinase C beta inhibitor LY333531 on neural and vascular function in rats with streptozotocin-induced diabetes. Clin Sci (Lond) 2002;103(3):311–321.Google Scholar
  59. 59.
    Cameron NE, Jack AM, Cotter MA. Effect of alpha-lipoic acid on vascular responses and nociception in diabetic rats. Free Radic Biol Med 2001;31(1):125–135.PubMedCrossRefGoogle Scholar
  60. 60.
    Tuttle KR, Anderson PW. A novel potential therapy for diabetic nephropathy and vascular complications: protein kinase C beta inhibition. Am J Kidney Dis 2003;42(3):456–465.PubMedCrossRefGoogle Scholar
  61. 61.
    Way KJ, Katai N, King GL. Protein kinase C and the development of diabetic vascular complications. Diabet Med 2001;18(12):945–959.PubMedCrossRefGoogle Scholar
  62. 62.
    Beckman JA, Goldfine AB, Gordon MB, Garrett LA, Creager MA. Inhibition of protein kinase C beta prevents impaired endothelium-dependent vasodilation caused by hyperglycemia in humans. Circ Res 2002;90(1):107–111.PubMedCrossRefGoogle Scholar
  63. 63.
    Heitzer T, Finckh B, Albers S, Krohn K, Kohlschutter A, Meinertz T. Beneficial effects of alpha-lipoic acid and ascorbic acid on endothelium-dependent, nitric oxide-mediated vasodilation in diabetic patients: relation to parameters of oxidative stress. Free Radic Biol Med 2001;31(1):53–61.PubMedCrossRefGoogle Scholar
  64. 64.
    Abuja PM, Albertini R. Methods for monitoring oxidative stress, lipid peroxidation and oxidation resistance of lipoproteins. Clin Chim Acta 2001;306(1–2):1–17.PubMedCrossRefGoogle Scholar
  65. 65.
    Onorato JM, Thorpe SR, Baynes JW. Immunohistochemical and ELISA assays for biomarkers of oxidative stress in aging and disease. Ann N Y Acad Sci 1998;854:277–290.PubMedCrossRefGoogle Scholar
  66. 66.
    Wu LL, Chiou CC, Chang PY, Wu JT. Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics. Clin Chim Acta 2004;339(1–2):1–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Oxidative stress biomarkers and antioxidant protocols. In: Armstrong D (Ed.)., Methods in Molecular Biology Volume 186. Totowa: Humana Press, 2002.Google Scholar
  68. 68.
    Miyata T, van Yprsele de Strihou C, Kurokawa K, Baynes JW. Alterations in nonenzymatic biochemistry in uremia: origin and significance of “carbonyl stress” in long-term uremic complications. Kidney Int 1999;55(2):389–399.Google Scholar
  69. 69.
    Suzuki D, Miyata T, Kurokawa K. Carbonyl stress. Contrib Nephrol 2001;134:36–45.PubMedCrossRefGoogle Scholar
  70. 70.
    Baynes JW, Thorpe SR. Glycoxidation and lipoxidation in atherogenesis. Free Radic Biol Med 2000;28(12):1708–1716.PubMedCrossRefGoogle Scholar
  71. 71.
    McCance DR, Dyer DG, Dunn JA, Bailie KE, Thorpe SR, Baynes JW, Lyons TJ. Maillard reaction products and their relation to complications in insulin-dependent diabetes mellitus. J Clin Invest 1993;91(6):2470–2478.PubMedCrossRefGoogle Scholar
  72. 72.
    Dyer DG, Dunn JA, Thorpe SR, Bailie KE, Lyons TJ, McCance DR, Baynes JW. Accumulation of Maillard reaction products in skin collagen in diabetes and aging. J Clin Invest 1993;91(6):2463–2469.PubMedCrossRefGoogle Scholar
  73. 73.
    Wells-Knecht MC, Lyons TJ, McCance DR, Thorpe SR, Baynes JW. Age-dependent increase in ortho-tyrosine and methionine sulfoxide in human skin collagen is not accelerated in diabetes. Evidence against a generalized increase in oxidative stress in diabetes. J Clin Invest 1997;100(4):839–846.Google Scholar
  74. 74.
    Wang LJ, Lee TS, Lee FY, Pai RC, Chau LY. Expression of heme oxygenase-1 in atherosclerotic lesions. Am J Pathol 1998;152:711–720.PubMedGoogle Scholar
  75. 75.
    Chung SS, Ho EC, Lam KS, Chung SK. Contribution of polyol pathway to diabetes-induced oxidative stress. J Am Soc Nephrol 2003;14(8 Suppl 3):S233–S236.PubMedCrossRefGoogle Scholar
  76. 76.
    Li JM, Shah AM. ROS generation by nonphagocytic NADPH oxidase: potential relevance in diabetic nephropathy. J Am Soc Nephrol 2003;14(8 Suppl 3):S221–S226.PubMedCrossRefGoogle Scholar
  77. 77.
    Maritim AC, Sanders RA, Watkins JB. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 2003;17(1):24–38.PubMedCrossRefGoogle Scholar
  78. 78.
    Lonn E, Yusuf S, Hoogwerf B, Pogue J, Yi Q, Zinman B, Bosch J, Dagenais G, Mann JF, Gerstein HC, HOPE Study, MICRO-HOPE Study. 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(11):1919–1927.Google Scholar
  79. 79.
    Chisolm GM, Steinberg D. The oxidative modification hypothesis of atherogenesis: an overview. Free Radic Biol Med 2000;28(12):1815–1826.PubMedCrossRefGoogle Scholar
  80. 80.
    Penn MS, Chisolm GM. Oxidized lipoproteins, altered cell function and atherosclerosis. Atherosclerosis 1994;108(Suppl):S21–S29.Google Scholar
  81. 81.
    Albertini R, Moratti R, De Luca G. Oxidation of low-density lipoprotein in atherosclerosis from basic biochemistry to clinical studies. Curr Mol Med 2002;2(6):579–592.PubMedCrossRefGoogle Scholar
  82. 82.
    Schlondorff D. Cellular mechanisms of lipid injury in the glomerulus. Am J Kidney Dis 1993;22(1):72–82.PubMedGoogle Scholar
  83. 83.
    Heeringa P, Tervaert JW. Role of oxidized low-density lipoprotein in renal disease. Curr Opin Nephrol Hypertens 2002;11(3):287–293.PubMedCrossRefGoogle Scholar
  84. 84.
    Lyons TJ, Li W, Wells-Knecht MC, Jokl R. Toxicity of mildly modified low-density lipoproteins to cultured retinal capillary endothelial cells and pericytes. Diabetes 1994;43(9):1090–1095.PubMedCrossRefGoogle Scholar
  85. 85.
    Jenkins AJ, Li W, Moller K, Klein RL, Fu MX, Baynes JW, Thorpe SR, Lyons TJ. Pre-enrichment of modified low density lipoproteins with alpha-tocopherol mitigates adverse effects on cultured retinal capillary cells. Curr Eye Res 1999;19(2):137–145.PubMedCrossRefGoogle Scholar
  86. 86.
    Lyons TJ, Jenkins AJ. Lipoprotein glycation and its metabolic consequences. Curr Opin Lipidol 1997;8(3):174–180.PubMedCrossRefGoogle Scholar
  87. 87.
    Jenkins AJ, Rowley KG, Lyons TJ, Best JD, Hill MA, Klein RL. Lipoproteins and diabetic microvascular complications. Curr Pharm Des 2004;10(27):3395–3418.PubMedCrossRefGoogle Scholar
  88. 88.
    Lyons TJ. Oxidized low density lipoproteins–a role in the pathogenesis of atherosclerosis in diabetes? Diabet Med 1991;8:411–419.PubMedCrossRefGoogle Scholar
  89. 89.
    Relou IA, Hackeng CM, Akkerman JW, Malle E. Low-density lipoprotein and its effect on human blood platelets. Cell Mol Life Sci 2003;60(5):961–971.PubMedGoogle Scholar
  90. 90.
    Kuo Hein TW, Liao JC, Kuo L. oxLDL specifically impairs endothelium-dependent, NO-mediated dilation of coronary arterioles. Am J Physiol Heart Circ Physiol 2000;278(1):H175–H183.Google Scholar
  91. 91.
    Bolz SS, Galle J, Derwand R, de Wit C, Pohl U. Oxidized LDL increases the sensitivity of the contractile apparatus in isolated resistance arteries for Ca(2+) via a rho- and rho kinase-dependent mechanism. Circulation 2000;102(19):2402–2410.PubMedGoogle Scholar
  92. 92.
    Lyons TJ, Klein RL, Baynes JW, Stevenson HC, Lopes-Virella MF. Stimulation of cholesteryl ester synthesis in human monocyte-derived macrophages by lipoproteins from Type 1 diabetic subjects: the influence of non-enzymatic glycosylation of low-density lipoproteins. Diabetologia 1987;30:916–923.PubMedCrossRefGoogle Scholar
  93. 93.
    Lopes-Virella MF, Klein RL, Lyons TJ, Stevenson HC, Witztum JL. Glycosylated low density lipoprotein enhances cholesteryl ester synthesis in human monocyte-derived macrophages. Diabetes 1988;37:550–557.PubMedCrossRefGoogle Scholar
  94. 94.
    Jenkins AJ, Velarde V, Klein RL, Joyce KC, Phillips KD, Mayfield RK, Lyons TJ, Jaffa AA. Native and modified LDL activate extracellular signal-regulated kinases in mesangial cells. Diabetes 2000;49(12):2160–2169.PubMedCrossRefGoogle Scholar
  95. 95.
    Velarde V, Jenkins AJ, Christopher J, Lyons TJ, Jaffa AA. Activation of MAPK by modified low-density lipoproteins in vascular smooth muscle cells. J Appl Physiol 2001;91(3): 1412–1420.PubMedGoogle Scholar
  96. 96.
    Lyons TJ, Li W, Wojciechowski B, Wells-Knecht MC, Wells-Knecht KJ, Jenkins AJ. Aminoguanidine and the effects of modified LDL on cultured retinal capillary cells. Invest Ophthalmol Vis Sci 2000;41:1176–1180.PubMedGoogle Scholar
  97. 97.
    Edwards IJ, Wagner JD, Litwak KN, Rudel LL, Cefalu WT. Glycation of plasma low density lipoproteins increases interaction with arterial proteoglycans. Diabetes Res Clin Pract 1999;46(1):9–18.PubMedCrossRefGoogle Scholar
  98. 98.
    Edwards IJ, Terry JG, Bell-Farrow AD, Cefalu WT. Improved glucose control decreases the interaction of plasma low-density lipoproteins with arterial proteoglycans. Metabolism 2002;51(10):1223–1229.PubMedCrossRefGoogle Scholar
  99. 99.
    Tsai EC, Hirsch IB, Brunzell JD, Chait A. Reduced plasma peroxyl radical trapping capacity and increased susceptibility of LDL to oxidation in poorly controlled IDDM. Diabetes 1994;43(8):1010–1014.PubMedCrossRefGoogle Scholar
  100. 100.
    Jenkins AJ, Klein RL, Chassereau CN, Hermayer KL, Lopes-Virella MF. LDL from patients with well-controlled IDDM is not more susceptible to in vitro oxidation. Diabetes 1996;45(6):762–767.PubMedCrossRefGoogle Scholar
  101. 101.
    Jenkins AJ, Thorpe SR, Alderson NL, Hermayer KL, Lyons TJ, King LP, et al. In vivo glycated LDL is not more susceptible to oxidation than non-glycated LDL in type 1 diabetes. Metabolism 2004;53(8):969–976.PubMedCrossRefGoogle Scholar
  102. 102.
    Jenkins AJ, Lyons TJ, Zheng D, Otvos JD, Lackland DT, McGee D, et al. Serum lipoproteins in the diabetes control and complications trial/epidemiology of diabetes intervention and complications cohort: associations with gender and glycemia. Diabetes Care 2003;26(3): 810–818.PubMedCrossRefGoogle Scholar
  103. 103.
    Jenkins AJ, Lyons TJ, Zheng D, Otvos JD, Lackland DT, McGee D, Garvey WT, Klein RL, DCCT/EDIC Research Group. Lipoproteins in the DCCT/EDIC cohort: associations with diabetic nephropathy. Kidney Int 2003;64(3):817–828.Google Scholar
  104. 104.
    Jenkins AJ, Lyons TJ, Zheng D, Lackland DT, McGee D, Garvey WT, Klein RL. Diabetic retinopathy and serum lipoprotein subclasses in the DCCT/EDIC Cohort. Invest Ophthalmol Vis Sci 2004;45(3):910–918.PubMedCrossRefGoogle Scholar
  105. 105.
    Nishi K, Itabe H, Uno M, Kitazato KT, Horiguchi H, Shinno K, Nagahiro S. Oxidized LDL in carotid plaques and plasma associates with plaque instability. Arterioscler Thromb Vasc Biol 2002;22(10):1649–1654.PubMedCrossRefGoogle Scholar
  106. 106.
    Ehara S, Ueda M, Naruko T, Haze K, Itoh A, Otsuka M, et al. Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation 2001;103(15):1955–1960.PubMedGoogle Scholar
  107. 107.
    Nordin Fredrikson G, Hedblad B, Berglund G, Nilsson J. Plasma oxidized LDL: a predictor for acute myocardial infarction? J Intern Med 2003;253(4):425–429.PubMedCrossRefGoogle Scholar
  108. 108.
    Tsutsui T, Tsutamoto T, Wada A, Maeda K, Mabuchi N, Hayashi M, et al. Plasma oxidized low-density lipoprotein as a prognostic predictor in patients with chronic congestive heart failure. J Am Coll Cardiol 2002;39(6):957–962.PubMedCrossRefGoogle Scholar
  109. 109.
    Holvoet P, Mertens A, Verhamme P, Bogaerts K, Beyens G, Verhaeghe R, et al. Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2001;21(5):844–848.PubMedGoogle Scholar
  110. 110.
    Ujihara N, Sakka Y, Takeda M, Hirayama M, Ishii A, Tomonaga O, et al. Association between plasma oxidized low-density lipoprotein and diabetic nephropathy. Diabetes Res Clin Pract 2002;58(2):109–114.PubMedCrossRefGoogle Scholar
  111. 111.
    Virella G, Thorpe SR, Alderson NL, Stephan EM, Atchley D, Wagner F, et al. Autoimmune response to advanced glycosylation end-products of human LDL. J Lipid Res 2003;44(3):487–493.PubMedCrossRefGoogle Scholar
  112. 112.
    Virella G, Atchley D, Koskinen S, Zheng D, Lopes-Virella MF, DCCT/EDIC Research Group. Proatherogenic and proinflammatory properties of immune complexes prepared with purified human oxLDL antibodies and human oxLDL. Clin Immunol 2002;105(1): 81–92.Google Scholar
  113. 113.
    Turk Z, Sesto M, Skodlar J, Ferencak G, Turk N, Stavljenic-Rukavina A. Soluble LDL-immune complexes in type 2 diabetes and vascular disease. Horm Metab Res 2002;34(4):196–201.PubMedCrossRefGoogle Scholar
  114. 114.
    Lopes-Virella MF, Virella G, Orchard TJ, Koskinen S, Evans RW, Becker DJ, et al. Antibodies to oxidized LDL and LDL-containing immune complexes as risk factors for coronary artery disease in diabetes mellitus. Clin Immunol 1999;90(2):165–172.PubMedCrossRefGoogle Scholar
  115. 115.
    Lopes-Virella MF, Virella G. The role of immune and inflammatory processes in the development of macrovascular disease in diabetes. Front Biosci 2003;8:s750–s768.PubMedCrossRefGoogle Scholar
  116. 116.
    Atchley DH, Lopes-Virella MF, Zheng D, Kenny D, Virella G. Oxidized LDL-anti-oxidized LDL immune complexes and diabetic nephropathy. Diabetologia 2002;45(11):1562–1571.PubMedCrossRefGoogle Scholar
  117. 117.
    Orchard TJ, Virella G, Forrest KY, Evans RW, Becker DJ, Lopes-Virella MF. Antibodies to oxidized LDL predict coronary artery disease in type 1 diabetes: a nested case-control study from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes 1999;48(7):1454–1458.PubMedCrossRefGoogle Scholar
  118. 118.
    Fam SS, Morrow JD. The isoprostanes: unique products of arachidonic acid oxidation–a review. Curr Med Chem 2003;10(17):1723–1740.PubMedCrossRefGoogle Scholar
  119. 119.
    Schwedhelm E, Boger RH. Application of gas chromatography-mass spectrometry for analysis of isoprostanes: their role in cardiovascular disease. Clin Chem Lab Med 2003;41(12):1552–1561.PubMedCrossRefGoogle Scholar
  120. 120.
    Cracowski JL, Durand T, Bessard G. Isoprostanes as a biomarker of lipid peroxidation in humans: physiology, pharmacology and clinical implications. Trends Pharmacol Sci 2002;23(8):360–366.PubMedCrossRefGoogle Scholar
  121. 121.
    Mezzetti A, Cipollone F, Cuccurullo F. Oxidative stress and cardiovascular complications in diabetes: isoprostanes as new markers on an old paradigm. Cardiovasc Res 2000;47(3): 475–488.PubMedCrossRefGoogle Scholar
  122. 122.
    Ikizler TA, Morrow JD, Roberts LJ, Evanson JA, Becker B, Hakim RM, Shyr Y, Himmelfarb J. Plasma F2-isoprostane levels are elevated in chronic hemodialysis patients. Clin Nephrol 2002;58(3):190–197.PubMedGoogle Scholar
  123. 123.
    Michoud E, Lecomte M, Lagarde M, Wiernsperger N. In vivo effect of 8-epi-PGF2alpha on retinal circulation in diabetic and non-diabetic rats. Prostaglandins Leukot Essent Fatty Acids 1998;59(6):349–355.PubMedCrossRefGoogle Scholar
  124. 124.
    Gardan B, Cracowski JL, Sessa C, Hunt M, Stanke-Labesque F, Devillier P, Bessard G. Vasoconstrictor effects of iso-prostaglandin F2alpha type-III (8-iso-prostaglandin F2alpha) on human saphenous veins. J Cardiovasc Pharmacol 2000;35(5):729–734.PubMedCrossRefGoogle Scholar
  125. 125.
    Hou X, Roberts LJ, Gobeil F, Taber D, Kanai K, Abran D, Brault S, Checchin D, Sennlaub F, Lachapelle P, Varma D, Chemtob S. Isomer-specific contractile effects of a series of synthetic F(2)-isoprostanes on retinal and cerebral microvasculature. Free Radic Biol Med 2004;36(2):163–172.PubMedCrossRefGoogle Scholar
  126. 126.
    Wilson AM, O’Neal D, Nelson CL, Prior DL, Best JD, Jenkins AJ. Comparison of arterial assessments in low and high vascular disease risk groups. Am J Hypertens 2004;17(4): 285–291.PubMedCrossRefGoogle Scholar
  127. 127.
    McVeigh GE, Allen PB, Morgan DR, Hanratty CG, Silke B. Nitric oxide modulation of blood vessel tone identified by arterial waveform analysis. Clin Sci (Lond) 2001;100(4): 387–393.CrossRefGoogle Scholar
  128. 128.
    Romney JS, Lewanczuk RZ. Vascular compliance is reduced in the early stages of type 1 diabetes. Diabetes Care 2001;24(12):2102–2106.PubMedCrossRefGoogle Scholar
  129. 129.
    McVeigh G, Brennan G, Hayes R, Cohn J, Finkelstein S, Johnston D. Vascular abnormalities in non-insulin-dependent diabetes mellitus identified by arterial waveform analysis. Am J Med 1993;95(4):424–430.PubMedCrossRefGoogle Scholar
  130. 130.
    Grey E, Bratteli C, Glasser SP, Alinder C, Finkelstein SM, Lindgren BR, Cohn JN. Reduced small artery but not large artery elasticity is an independent risk marker for cardiovascular events. Am J Hypertens 2003;16(4):265–269.PubMedCrossRefGoogle Scholar
  131. 131.
    Jialal I, Devaraj S, Venugopal SK. Oxidative stress, inflammation, and diabetic vasculopathies: the role of alpha tocopherol therapy. Free Radic Res 2002;36(12):1331–1336.PubMedCrossRefGoogle Scholar
  132. 132.
    Upritchard JE, Schuurman CR, Wiersma A, Tijburg LB, Coolen SA, Rijken PJ, Wiseman SA. Spread supplemented with moderate doses of vitamin E and carotenoids reduces lipid peroxidation in healthy, nonsmoking adults. Am J Clin Nutr 2003;78(5):985–992.PubMedGoogle Scholar
  133. 133.
    Desideri G, Croce G, Tucci M, Passacquale G, Broccoletti S, Valeri L, Santucci A, Ferri C. Effects of bezafibrate and simvastatin on endothelial activation and lipid peroxidation in hypercholesterolemia: evidence of different vascular protection by different lipid-lowering treatments. J Clin Endocrinol Metab 2003;88(11):5341–5347.PubMedCrossRefGoogle Scholar
  134. 134.
    Leonhardt W. Concentrations of antioxidative vitamins in plasma and low-density lipoprotein of diabetic patients. In: Packer L, Rosen P, Tritschler HJ, King GL (Eds). Antioxidants in Diabetes Management. New York: Marcel Decker, 2000, pp. 65–76.Google Scholar
  135. 135.
    Cohen J, Jenkins AJ, Karschimkus C, Qing S, Lee CT, O’Dea K, Best JD, Rowley KG. Paraoxonase and other coronary risk factors in a community-based cohort. Redox Rep 2002;7(5):304–307.PubMedCrossRefGoogle Scholar
  136. 136.
    Jerums G, Panagiotopoulos S, Forbes J, Osicka T, Cooper M. Evolving concepts in advanced glycation, diabetic nephropathy, and diabetic vascular disease. Arch Biochem Biophys 2003;419(1):55–62.PubMedCrossRefGoogle Scholar
  137. 137.
    Forbes JM, Cooper ME, Oldfield MD, Thomas MC. Role of advanced glycation end products in diabetic nephropathy. J Am Soc Nephrol 2003;14(8 Suppl 3):S254–S258.PubMedCrossRefGoogle Scholar
  138. 138.
    Silacci P. Advanced glycation end-products as a potential target for treatment of cardiovascular disease. J Hypertens 2002;20(8):1483–1485.PubMedCrossRefGoogle Scholar
  139. 139.
    Stern DM, Yan SD, Yan SF, Schmidt AM. Receptor for advanced glycation endproducts (RAGE) and the complications of diabetes. Ageing Res Rev 2002;1(1):1–15.PubMedCrossRefGoogle Scholar
  140. 140.
    Wendt T, Bucciarelli L, Qu W, Lu Y, Yan SF, Stern DM, Schmidt AM. Receptor for advanced glycation endproducts (RAGE) and vascular inflammation:insights into the pathogenesis of macrovascular complications in diabetes. Curr Atheroscler Rep 2002;4(3):228–237.PubMedCrossRefGoogle Scholar
  141. 141.
    Vlassara H, Palace MR. Diabetes and advanced glycation endproducts. J Intern Med 2002;251(2):87–101.PubMedCrossRefGoogle Scholar
  142. 142.
    Wautier JL, Guillausseau PJ. Advanced glycation end products, their receptors and diabetic angiopathy. Diabetes Metab 2001;27(5 Pt 1):535–542.PubMedGoogle Scholar
  143. 143.
    Beisswenger PJ, Makita Z, Curphey TJ, Moore LL, Jean S, Brinck-Johnsen T, Bucala R, Vlassara H. Formation of immunochemical advanced glycosylation end products precedes and correlates with early manifestations of renal and retinal disease in diabetes. Diabetes 1995;44:824–829.PubMedCrossRefGoogle Scholar
  144. 144.
    Requena JR, Ahmed MU, Reddy SR, Fountain CW, Degenhardt TP, Jenkins AJ, Smyth B, Lyons TJ, Thorpe SR. Detection of AGE-lipids in vivo: glycation and carboxymethylation of aminophosholipids in red-cell membranes. Proceedings of the 1997 International Malliard Meeting.Google Scholar
  145. 145.
    Lyons TJ, Requena JR, Fountain CW, Jenkins AJ, Perez CP, Gates D, Hermayer KL, King LP, Baynes JW, Thorpe SR. Glycoxidation and lipoxidation products in red blood cell membranes in poorly controlled diabetes. Diabetologia 1997;40(Suppl 1):A589.Google Scholar
  146. 146.
    Jenkins AJ, Lyons TJ, Smyth B, Requena JR, Fountain CW, Dagenhart T, Hermayer KL, Phillips KD, King LP, Baynes JW, Thorpe SR. Glycoxidation and lipoxidation products in red blood cell membranes in IDDM–relationship to glycemic control and microvascular complications. Diabetes 1998;47(Suppl 1):A127.Google Scholar
  147. 147.
    Berg TJ, Bangstad HJ, Torjesen PA, Osterby R, Bucala R, Hanssen KF. Advanced glycation end products in serum predict changes in the kidney morphology of patients with insulin-dependent diabetes mellitus. Metabolism 1997;46:661–665.PubMedCrossRefGoogle Scholar
  148. 148.
    Berg TJ, Torjesen PA, Dahl-Jørgensen K, Hanssen KF. Increased serum levels of AGEs in serum from children and adolescents with Type 1 diabetes. Diabetes Care 1997;21: 1006–1008.CrossRefGoogle Scholar
  149. 149.
    Kilhovd BK, Berg TJ, Birkeland KI, Thorsby P, Hanssen KF. Serum levels of advanced glycation end products are increased in patients with Type 2 diabetes and coronary heart disease. Diabetes Care 1999;22:1543–1548.PubMedCrossRefGoogle Scholar
  150. 150.
    Berg TJ, Snorgaard O, Faber J, Torjesen PA, Hildebrandt P, Mehlsen JK, Hanssen KF. Serum levels of AGEs are associated with left ventricular diastolic function in patients with Type 1 diabetes. Diabetes Care 1999;22:1186–1190.PubMedCrossRefGoogle Scholar
  151. 151.
    Kilhovd BK, Giardino I, Torjesen PA, Birkeland KI, Berg TJ, Thornalley PJ, Brownlee M, Hanssen KF. Increased serum levels of the specific AGE-compound methylglyoxal-derived hydroimidazolone in patients with type 2 diabetes. Metabolism 2003;52(2):163–167.PubMedCrossRefGoogle Scholar
  152. 152.
    Tan KC, Chow WS, Ai VH, Metz C, Bucala R, Lam KS. Advanced glycation end products and endothelial dysfunction in type 2 diabetes. Diabetes Care 2002;25(6):1055–1059.PubMedCrossRefGoogle Scholar
  153. 153.
    Buss H, Chan TP, Sluis KB, Domigan NM, Winterbourn CC. Protein carbonyl measurement by a sensitive ELISA method. Free Rad Res 1997;23:361–366.Google Scholar
  154. 154.
    Winterbourn CC, Buss IH, Chan TP, Plank LD, Clark MA, Windsor JA. Protein carbonyl measurements show evidence of early oxidative stress in critically ill patients. Crit Care Med 2000;28(1):143–149.PubMedCrossRefGoogle Scholar
  155. 155.
    Martin-Gallan P, Carrascosa A, Gussinye M, Dominguez C. Biomarkers of diabetes-associated oxidative stress and antioxidant status in young diabetic patients with or without subclinical complications. Free Radic Biol Med 2003;34(12):1563–1574.PubMedCrossRefGoogle Scholar
  156. 156.
    Odetti P, Garibaldi S, Noberasco G, Aragno I, Valentini S, Traverso N, Marinari UM. Levels of carbonyl groups in plasma proteins of type 2 diabetes mellitus subjects. Acta Diabetol 1999;36(4):179–183.PubMedCrossRefGoogle Scholar
  157. 157.
    Kalogerakis G, Baker AM, Christov S, Dwyer K, Lee P, Buss H, Winterbourn C, Best JD, Jenkins AJ. Oxidative stress and high density lipoprotein (HDL) function in end stage renal disease (ESRD) and type 1 diabetes mellitus. Annual Scientific Meeting of the Australian Atherosclerosis Society, Sydney, Australia, November 2000.Google Scholar
  158. 158.
    Naito C, Kajita M, Niwa T. Determination of glutathionyl hemoglobin in hemodialysis patients using electrospray ionization liquid chromatography-mass spectrometry. J Chromatogr B–Biomed Sci Appl 1999;731(1):121–124.Google Scholar
  159. 159.
    Bursell SE, King GL. The potential use of glutathionyl hemoglobin as a clinical marker of oxidative stress. Clin Chem 2000;46(2):145–146.PubMedGoogle Scholar
  160. 160.
    Niwa T, Naito C, Mawjood AHM, Imai K. Increased glutathionyl hemoglobin in diabetes mellitus and hyperlipidemia demonstrated by liquid chromatography/electronspray ionization-mass spectroscopy. Clin Chem 2000;46:82–88.PubMedGoogle Scholar
  161. 161.
    Takayama F, Tsutsui S, Horie M, Shimokata K, Niwa T. Glutathionyl hemoglobin in uremic patients undergoing hemodialysis and continuous ambulatory peritoneal dialysis. Kidney Int Suppl 2001;78:S155–S158.PubMedCrossRefGoogle Scholar
  162. 162.
    Naito C, Niwa T. Analysis of glutathionyl hemoglobin levels in diabetic patients by electrospray ionization liquid chromatography–mass spectrometry: effect of vitamin E administration. J Chromatogr B - Biomed Sci Appl 2000;746(1):91–94.PubMedCrossRefGoogle Scholar
  163. 163.
    Maytin M, Leopold J, Loscalzo J. Oxidant stress in the vasculature. Curr Atheroscler Rep 1999;1(2):156–164.PubMedCrossRefGoogle Scholar
  164. 164.
    Fukai T, Folz RJ, Landmesser U, Harrison DG. Extracellular superoxide dismutase and cardiovascular disease. Cardiovasc Res 2002;55(2):239–249.PubMedCrossRefGoogle Scholar
  165. 165.
    Cooke CL, Davidge ST. Endothelial-dependent vasodilation is reduced in mesenteric arteries from superoxide dismutase knockout mice. Cardiovasc Res 2003;60(3):635–642.PubMedCrossRefGoogle Scholar
  166. 166.
    Du Y, Miller CM, Kern TS. Hyperglycemia increases mitochondrial superoxide in retina and retinal cells. Free Radic Biol Med 2003;35(11):1491–1499.PubMedCrossRefGoogle Scholar
  167. 167.
    Kang JH. Modification and inactivation of human Cu, Zn-superoxide dismutase by methylglyoxal. Mol Cells 2003;15(2):194–199.PubMedGoogle Scholar
  168. 168.
    Gupta S, Chough E, Daley J, Oates P, Tornheim K, Ruderman NB, Keaney JF Jr. Hyperglycemia increases endothelial superoxide that impairs smooth muscle cell Na+- K+-ATPase activity. Am J Physiol Cell Physiol 2002;282(3):C560–C566.PubMedGoogle Scholar
  169. 169.
    Kinscherf R, Deigner HP, Usinger C, Pill J, Wagner M, Kamencic H, Hou D, Chen M, Schmiedt W, Schrader M, Kovacs G, Kato K, Metz J. Induction of mitochondrial manganese superoxide dismutase in macrophages by oxidized LDL: its relevance in atherosclerosis of humans and heritable hyperlipidemic rabbits. FASEB J 1997;11(14): 1317–1328.PubMedGoogle Scholar
  170. 170.
    Voinea M, Georgescu A, Manea A, Dragomir E, Manduteanu I, Popov D, Simionescu M. Superoxide dismutase entrapped-liposomes restore the impaired endothelium-dependent relaxation of resistance arteries in experimental diabetes. Eur J Pharmacol 2004;484(1):111–118.PubMedCrossRefGoogle Scholar
  171. 171.
    Zanetti M, Sato J, Katusic ZS, O’Brien T. Gene transfer of superoxide dismutase isoforms reverses endothelial dysfunction in diabetic rabbit aorta. Am J Physiol Heart Circ Physiol 2001;280(6):H2516–H2523.PubMedGoogle Scholar
  172. 172.
    Rodriguez-Manas L, Lopez-Doriga P, Petidier R, Neira M, Solis J, Pavon I, Peiro C, Sanchez-Ferrer CF. Effect of glycaemic control on the vascular nitric oxide system in patients with type 1 diabetes. J Hypertens 2003;21(6):1137–1143.PubMedCrossRefGoogle Scholar
  173. 173.
    Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000;404(6779): 787–790.PubMedCrossRefGoogle Scholar
  174. 174.
    Kotake M, Shinohara R, Kato K, Hayakawa N, Hayashi R, Uchimura K, Makino M, Nagata M, Kakizawa H, Nakagawa H, Nagasaka A, Itoh M. Reduction of activity, but no decrease in concentration, of erythrocyte Cu, Zn-superoxide dismutase by hyperglycaemia in diabetic patients. Diabet Med 1998;15(8):668–671.PubMedCrossRefGoogle Scholar
  175. 175.
    Bhatia S, Shukla R, Venkata Madhu S, Kaur Gambhir J, Madhava Prabhu K. Antioxidant status, lipid peroxidation and nitric oxide end products in patients of type 2 diabetes mellitus with nephropathy. Clin Biochem 2003;36(7):557–562.PubMedCrossRefGoogle Scholar
  176. 176.
    Dincer Y, Akcay T, Ilkova H, Alademir Z, Ozbay G. DNA damage and antioxidant defense in peripheral leukocytes of patients with Type 1 diabetes mellitus. Mutat Res 2003;527(1–2): 49–55.PubMedGoogle Scholar
  177. 177.
    Muchova J, Liptakova A, Orszaghova Z, Garaiova I, Tison P, Carsky J, Durackova Z. Antioxidant systems in polymorphonuclear leucocytes of Type 2 diabetes mellitus. Diabet Med 1999;16(1):74–78.PubMedCrossRefGoogle Scholar
  178. 178.
    Skrha J, Hodinar A, Kvasnicka J, Hilgertova J. Relationship of oxidative stress and fibrinolysis in diabetes mellitus. Diabet Med 1996;13(9):800–805.PubMedCrossRefGoogle Scholar
  179. 179.
    Kedziora-Kornatowska KZ, Luciak M, Blaszczyk J, Pawlak W. Lipid peroxidation and activities of antioxidant enzymes in erythrocytes of patients with non-insulin dependent diabetes with or without diabetic nephropathy. Nephrol Dial Transplant 1998;13(11):2829–2832.PubMedCrossRefGoogle Scholar
  180. 180.
    Merzouk S, Hichami A, Madani S, Merzouk H, Berrouiguet AY, Prost J, Moutairou K, Chabane-Sari N, Khan NA. Antioxidant status and levels of different vitamins determined by high performance liquid chromatography in diabetic subjects with multiple complications. Gen Physiol Biophys 2003;22(1):15–27.PubMedGoogle Scholar
  181. 181.
    Memisogullari R, Taysi S, Bakan E, Capoglu I. Antioxidant status and lipid peroxidation in Type 1I diabetes mellitus. Cell Biochem Funct 2003;21(3):291–296.PubMedCrossRefGoogle Scholar
  182. 182.
    Roussel AM, Kerkeni A, Zouari N, Mahjoub S, Matheau JM, Anderson RA. Antioxidant effects of zinc supplementation in Tunisians with type 2 diabetes mellitus. J Am Coll Nutr 2003;22(4):316–321.PubMedGoogle Scholar
  183. 183.
    Ruiz C, Alegria A, Barbera R, Farre R, Lagarda MJ. Lipid peroxidation and antioxidant enzyme activities in patients with type 1 diabetes mellitus. Scand J Clin Lab Invest 1999;59(2):99–105.PubMedCrossRefGoogle Scholar
  184. 184.
    Akkus I, Kalak S, Vural H, Caglayan O, Menekse E, Can G, Durmus B. Leukocyte lipid peroxidation, superoxide dismutase, glutathione peroxidase and serum and leukocyte vitamin C levels of patients with Type 1I diabetes mellitus. Clin Chim Acta 1996;244(2):221–227.PubMedCrossRefGoogle Scholar
  185. 185.
    Leonard MB, Lawton K, Watson ID, Patrick A, Walker A, MacFarlane I. Cigarette smoking and free radical activity in young adults with insulin-dependent diabetes. Diabet Med 1995;12(1):46–50.PubMedCrossRefGoogle Scholar
  186. 186.
    Kimura F, Hasegawa G, Obayashi H, Adachi T, Hara H, Ohta M, Fukui M, Kitagawa Y, Park H, Nakamura N, Nakano K, Yoshikawa T. Serum extracellular superoxide dismutase in patients with type 2 diabetes: relationship to the development of micro- and macrovascular complications. Diabetes Care 2003;26(4):1246–1250.PubMedCrossRefGoogle Scholar
  187. 187.
    Palanduz S, Ademoglu E, Gokkusu C, Tamer S. Plasma antioxidants and type 2 diabetes mellitus. Res Commun Mol Pathol Pharmacol 2001;109(5–6):309–318.PubMedGoogle Scholar
  188. 188.
    Martin-Gallan P, Carrascosa A, Gussinye M, Dominguez C. Biomarkers of diabetes-associated oxidative stress and antioxidant status in young diabetic patients with or without subclinical complications. Free Radic Biol Med 2003;34(12):1563–1574.PubMedCrossRefGoogle Scholar
  189. 189.
    Landmesser U, Merten R, Spiekermann S, Buttner K, Drexler H, Hornig B. Vascular extracellular superoxide dismutase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation. Circulation 2000;101(19):2264–2270.PubMedGoogle Scholar
  190. 190.
    Wang XL, Adachi T, Sim AS, Wilcken DE. Plasma extracellular superoxide dismutase levels in an Australian population with coronary artery disease. Arterioscler Thromb Vasc Biol 1998;18(12):1915–1921.PubMedGoogle Scholar
  191. 191.
    Jandric-Balen M, Bozikov V, Bistrovic D, Jandric I, Bozikov J, Romic Z, Balen I. Antioxidant enzymes activity in patients with peripheral vascular disease, with and without presence of diabetes mellitus. Coll Anthropol 2003;27(2):735–743.Google Scholar
  192. 192.
    Blankenberg S, Rupprecht HJ, Bickel C, Torzewski M, Hafner G, Tiret L, Smieja M, Cambien F, Meyer J, Lackner KJ, AtheroGene Investigators. Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. N Engl J Med 2003;23;349(17):1605–1613.Google Scholar
  193. 193.
    Strokov IA, Bursa TR, Drepa OI, Zotova EV, Nosikov VV, Ametov AS. Predisposing genetic factors for diabetic polyneuropathy in patients with type 1 diabetes: a population-based case-control study. Acta Diabetol 2003;40(Suppl 2):S375–S379.PubMedCrossRefGoogle Scholar
  194. 194.
    Nomiyama T, Tanaka Y, Piao L, Nagasaka K, Sakai K, Ogihara T, Nakajima K, Watada H, Kawamori R. The polymorphism of manganese superoxide dismutase is associated with diabetic nephropathy in Japanese type 2 diabetic patients. J Hum Genet 2003;48(3):138–141.PubMedGoogle Scholar
  195. 195.
    Ukkola O, Erkkila PH, Savolainen MJ, Kesaniemi YA. Lack of association between polymorphisms of catalase, copper–zinc superoxide dismutase (SOD), extracellular SOD and endothelial nitric oxide synthase genes and macroangiopathy in patients with type 2 diabetes mellitus. J Intern Med 2001;249(5):451–459.PubMedCrossRefGoogle Scholar
  196. 196.
    Mackness MI, Durrington PN. HDL, its enzymes and its potential to influence lipid peroxidation. Atherosclerosis 1995;115:243–253.PubMedCrossRefGoogle Scholar
  197. 197.
    Mackness MI, Mackness B, Durrington PN, Connelly PW, Hegele RA. Paraoxonase: biochemistry, genetics and relationship to plasma lipoproteins. Genetics Mol Biol 1996:69–76.Google Scholar
  198. 198.
    Mackness MI, Mackness B, Durrington PN. Paraoxonase and coronary heart disease. Atheroscler Suppl 2002;3(4):49–55.PubMedCrossRefGoogle Scholar
  199. 199.
    Durrington PN, Mackness B, Mackness MI. Paraoxonase and atherosclerosis. Arterioscler Thromb Vasc Biol 2001;21(4):473–480.PubMedGoogle Scholar
  200. 200.
    Van Lenten BJ, Wagner AC, Nayak DP, Hama S, Navab M, Fogelman AM. High-density lipoprotein loses its anti-inflammatory properties during acute influenza A infection. Circulation 2001;103(18):2283–2288.PubMedGoogle Scholar
  201. 201.
    Durrington PN, Mackness B, Mackness MI. The hunt for nutritional and pharmacological modulators of paraoxonase. Arterioscler Thromb Vasc Biol 2002;22(8):1248–1250.PubMedCrossRefGoogle Scholar
  202. 202.
    Mackness B, Durrington P, McElduff P, Yarnell J, Azam N, Watt M, Mackness M. Low paraoxonase activity predicts coronary events in the Caerphilly Prospective Study. Circulation 2003;107(22):2775–2779.PubMedCrossRefGoogle Scholar
  203. 203.
    Mackness B, Durrington PN, Mackness MI. The paraoxonase gene family and coronary heart disease. Curr Opin Lipidol 2002;13(4):357–362.PubMedCrossRefGoogle Scholar
  204. 204.
    Inoue M, Suehiro T, Nakamura T, Ikeda Y, Kumon Y, Hashimoto K. Serum arylesterase/diazoxonase activity and genetic polymorphisms in patients with type 2 diabetes. Metabolism 2000;49(11):1400–1405.PubMedCrossRefGoogle Scholar
  205. 205.
    Mackness B, Durrington P, Abuashia B, Boulton A, Mackness M. Low PON activity in Type 2 diabetes mellitus complicated by retinopathy. Clin Sci 2000;98:355–363.PubMedCrossRefGoogle Scholar
  206. 206.
    Ikeda Y, Suehiro T, Inoue M, Nakauchi Y, Morita T, Arii K, et al. Serum paraoxonase activity and its relationship to diabetic complications in patients with non-insulin-dependent diabetes mellitus. Metabolism 1998;47(5):598–602.PubMedCrossRefGoogle Scholar
  207. 207.
    Mackness MI, Harty D, Bhatnagar D, Winocour PH, Arrol S, Ishola M, et al. Serum paraoxonase activity in familial hypercholesterolaemia and insulin-dependent diabetes mellitus. Atherosclerosis 1990;86:193–199.CrossRefGoogle Scholar
  208. 208.
    Kordonouri O, James RW, Bennetts B, Chan A, Kao YL, Danne T, et al. Modulation by blood glucose levels of activity and concentration of paraoxonase in young patients with type 1 diabetes mellitus. Metabolism 2001;50(6):657–660.PubMedCrossRefGoogle Scholar
  209. 209.
    Kuremoto K, Watanabe Y, Ohmura H, Shimada K, Mokuno H, Daida H. R/R genotype of human paraoxonase (PON1) is more protective against lipoprotein oxidation and coronary artery disease in Japanese subjects. J Atheroscler Thromb 2003;10(2):85–92.PubMedGoogle Scholar
  210. 210.
    Malin R, Jarvinen O, Sisto T, Koivula T, Lehtimaki T. Paraoxonase producing PON1 gene M/L55 polymorphism is related to autopsy-verified artery-wall atherosclerosis. Atherosclerosis 2001;157(2):301–307.PubMedCrossRefGoogle Scholar
  211. 211.
    Hu Y, Tian H, Liu R. Gln-Arg192 polymorphism of paraoxonase 1 is associated with carotid intima-media thickness in patients of type 2 diabetes mellitus of Chinese. Diabetes Res Clin Pract 2003;61(1):21–27.PubMedCrossRefGoogle Scholar
  212. 212.
    Koch M, Hering S, Barth C, Ehren M, Enderle MD, Pfohl M. Paraoxonase 1 192 Gln/Arg gene polymorphism and cerebrovascular disease: interaction with type 2 diabetes. Exp Clin Endocrinol Diabetes 2001;109(3):141–145.PubMedCrossRefGoogle Scholar
  213. 213.
    Pfohl M, Koch M, Enderle MD, Kuhn R, Fullhase J, Karsch KR, et al. Paraoxonase 192 Gln/Arg gene polymorphism, coronary artery disease, and myocardial infarction in type 2 diabetes. Diabetes 1999;483:623–627.CrossRefGoogle Scholar
  214. 214.
    James RW, Leviev I, Ruiz J, Passa P, Froguel P, Garin MC. Promoter polymorphism T(-107) C of the paraoxonase PON1 gene is a risk factor for coronary heart disease in type 2 diabetic patients. Diabetes 2000;49(8):1390–1393.PubMedCrossRefGoogle Scholar
  215. 215.
    Osei-Hyiaman D, Hou L, Mengbai F, Zhiyin R, Zhiming Z, Kano K. Coronary artery disease risk in Chinese type 2 diabetics: is there a role for paraxonase 1 gene (Q192R) polymorphism? Eur J Endocrinol 2001;144(6):639–644.PubMedCrossRefGoogle Scholar
  216. 216.
    Pinizzotto M, Castillo E, Fiaux M, Temler E, Gaillard RC, Ruiz J. Paraoxonase2 polymorphisms are associated with nephropathy in Type 1I diabetes. Diabetologia 2001;44(1): 104–107.PubMedCrossRefGoogle Scholar
  217. 217.
    Malin R, Laine S, Rantalaiho V, Wirta O, Pasternack A, Jokela H, Alho H, Koivula T, Lehtimaki T. Lipid peroxidation is increased in paraoxonase L55 homozygotes compared with M-allele carriers. Free Radic Res 2001;34(5):477–484.PubMedCrossRefGoogle Scholar
  218. 218.
    Malin R, Rantalaiho V, Huang XH, Wirta O, Pasternack A, Leinonen JS, Alho H, Jokela H, Koivula T, Tanaka T, Okada K, Ochi H, Toyokuni S, Lehtimaki T. Association between M/L55-polymorphism of paraoxonase enzyme and oxidative DNA damage in patients with type 2 diabetes mellitus and in control subjects. Hum Genet 1999;105(1–2):179–180.PubMedGoogle Scholar
  219. 219.
    Araki S, Makita Y, Canani L, Ng D, Warram JH, Krolewski AS. Polymorphisms of human paraoxonase 1 gene (PON1) and susceptibility to diabetic nephropathy in Type 1 diabetes mellitus. Diabetologia 2000;43(12):1540–1543.PubMedCrossRefGoogle Scholar
  220. 220.
    Garin MCB, James RW, Dussoix P, Blanche H, Passa P, Froguel P, et al. Paraoxonase polymorphism Met-Leu54 is associated with modified serum concentrations of the enzyme: a possible link between the paraoxonase gene and increased risk of cardiovascular disease in diabetes. J Clin Invest 1997;99:62–66.PubMedCrossRefGoogle Scholar
  221. 221.
    Kleemola P, Freese R, Jauhiainen M, Pahlman R, Alfthan G, Mutanen M. Dietary determinants of serum paraoxonase activity in healthy humans. Atherosclerosis 2002;160(2):425–432.PubMedCrossRefGoogle Scholar
  222. 222.
    Aviram M, Dornfeld L, Rosenblat M, Volkova N, Kaplan M, Coleman R, Hayek T, Presser D, Fuhrman B. Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice. Am J Clin Nutr 2000;71(5):1062–1076.PubMedGoogle Scholar
  223. 223.
    Nishio E, Watanabe Y. Cigarette smoke extract inhibits plasma paraoxonase activity by modification of the enzyme’s free thiols. Biochem Biophys Res Comm 1997;236(2):289–293.PubMedCrossRefGoogle Scholar
  224. 224.
    Tomas M, Senti M, Garcia-Faria F, Vila J, Torrents A, Covas M, et al. Effect of simvastatin therapy on PON activity and related lipoproteins in familial hypercholesterolemic patients. Arterioscler Thromb Vasc Biol 2000;20:2113–2119.PubMedGoogle Scholar
  225. 225.
    Balogh Z, Seres I, Harangi M, Kovacs P, Kakuk G, Paragh G. Gemfibrozil increases paraoxonase activity in type 2 diabetic patients. A new hypothesis of the beneficial action of fibrates? Diabetes Metab 2001;27(5 Pt 1):604–610.Google Scholar
  226. 226.
    Sutherland WH, Manning PJ, de Jong SA, Allum AR, Jones SD, Williams SM. Hormone-replacement therapy increases serum paraoxonase arylesterase activity in diabetic postmenopausal women. Metabolism 2001;50(3):319–324.PubMedCrossRefGoogle Scholar
  227. 227.
    Brennan ML, Hazen SL. Emerging role of myeloperoxidase and oxidant stress markers in cardiovascular risk assessment. Curr Opin Lipidol 2003;14(4):353–359.PubMedCrossRefGoogle Scholar
  228. 228.
    Uchimura K, Nagasaka A, Hayashi R, Makino M, Nagata M, Kakizawa H, Kobayashi T, Fujiwara K, Kato T, Iwase K, Shinohara R, Kato K, Itoh M. Changes in superoxide dismutase activities and concentrations and myeloperoxidase activities in leukocytes from patients with diabetes mellitus. J Diab Compl 1999;13(5–6):264–270.CrossRefGoogle Scholar
  229. 229.
    Sato N, Shimizu H, Suwa K, Shimomura Y, Kobayashi I, Mori M. MPO activity and generation of active O2 species in leukocytes from poorly controlled diabetic patients. Diabetes Care 1992;15(8):1050–1052.PubMedCrossRefGoogle Scholar
  230. 230.
    Thukkani AK, McHowat J, Hsu FF, Brennan ML, Hazen SL, Ford DA. Identification of alpha-chloro fatty aldehydes and unsaturated lysophosphatidylcholine molecular species in human atherosclerotic lesions. Circulation 2003;108(25):3128–3133.PubMedCrossRefGoogle Scholar
  231. 231.
    Kutter D, Devaquet P, Vanderstocken G, Paulus JM, Marchal V, Gothot A. Consequences of total and subtotal myeloperoxidase deficiency: risk or benefit? Acta Haematol 2000;104(1):10–15.PubMedCrossRefGoogle Scholar
  232. 232.
    Nikpoor B, Turecki G, Fournier C, Theroux P, Rouleau GA. A functional myeloperoxidase polymorphic variant is associated with coronary artery disease in French-Canadians. Am Heart J 2001;142(2):336–339.PubMedCrossRefGoogle Scholar
  233. 233.
    Makela R, Karhunen PJ, Kunnas TA, Ilveskoski E, Kajander OA, Mikkelsson J, Perola M, Penttila A, Lehtimaki T. Myeloperoxidase gene variation as a determinant of atherosclerosis progression in the abdominal and thoracic aorta: an autopsy study. Lab Invest 2003;83(7):919–925.PubMedCrossRefGoogle Scholar
  234. 234.
    Makela R, Laaksonen R, Janatuinen T, Vesalainen R, Nuutila P, Jaakkola O, Knuuti J, Lehtimaki T. Myeloperoxidase gene variation and coronary flow reserve in young healthy men. J Biomed Sci 2004;11(1):59–64.PubMedCrossRefGoogle Scholar
  235. 235.
    Hoy A, Leininger-Muller B, Poirier O, Siest G, Gautier M, Elbaz A, Amarenco P, Visvikis S. Myeloperoxidase polymorphisms in brain infarction. Association with infarct size and functional outcome. Atherosclerosis 2003;167(2):223–230.Google Scholar
  236. 236.
    Pecoits-Filho R, Stenvinkel P, Marchlewska A, Heimburger O, Barany P, Hoff CM, Holmes CJ, Suliman M, Lindholm B, Schalling M, Nordfors L. A functional variant of the myeloperoxidase gene is associated with cardiovascular disease in end-stage renal disease patients. Kidney Int 2003;84(Suppl):S172–S176.Google Scholar
  237. 237.
    Zhang R, Brennan ML, Fu X, Aviles RJ, Pearce GL, Penn MS, Topol EJ, Sprecher DL, Hazen SL. Association between myeloperoxidase levels and risk of coronary artery disease. JAMA 2001;286(17):2136–2142.PubMedCrossRefGoogle Scholar
  238. 238.
    Brennan ML, Penn MS, Van Lente F, Nambi V, Shishehbor MH, Aviles RJ, Goormastic M, Pepoy ML, McErlean ES, Topol EJ, Nissen SE, Hazen SL. Prognostic value of myeloperoxidase in patients with chest pain. N Engl J Med 2003;349(17):1595–1604.PubMedCrossRefGoogle Scholar
  239. 239.
    Shishehbor MH, Aviles RJ, Brennan ML, Fu X, Goormastic M, Pearce GL, Gokce N, Keaney JF Jr, Penn MS, Sprecher DL, Vita JA, Hazen SL. Association of nitrotyrosine levels with cardiovascular disease and modulation by statin therapy. JAMA 2003;289(13):1675–1680.PubMedCrossRefGoogle Scholar
  240. 240.
    Shishehbor MH, Brennan ML, Aviles RJ, Fu X, Penn MS, Sprecher DL, Hazen SL. Statins promote potent systemic antioxidant effects through specific inflammatory pathways. Circulation 2003;108(4):426–431.PubMedCrossRefGoogle Scholar
  241. 241.
    Bursell SE, King G. Protein kinase C, development of diabetic vascular complications, and role of Vitamin E in preventing these abnormalities. In: Packer L, Rosen P, Tritschler HJ, King GL (Eds). Antioxidants in Diabetes Management. New York: Marcel Decker, 2000, pp. 241–264.Google Scholar
  242. 242.
    Bursell SE, Clermont AC, Aiello LP, Aiello LM, Schlossman DK, Feener EP, Laffel L, King GL. High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes. Diabetes Care 1999;22(8):1245–1251.PubMedCrossRefGoogle Scholar
  243. 243.
    Skyrme-Jones RA, O’Brien RC, Berry KL, Meredith IT. Vitamin E supplementation improves endothelial function in Type 1 diabetes mellitus: a randomized, placebo-controlled study. J Am Coll Cardiol 2000;36(1):94–102.PubMedCrossRefGoogle Scholar
  244. 244.
    MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20, 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360(9326):23–33.Google Scholar
  245. 245.
    Nutrition recommendations and principles for people with diabetes mellitus. Diabetes Care 2000;23(Suppl 1):S43–S46.Google Scholar
  246. 246.
    Bowry VW, Ingold KU, Stocker R. Vitamin E in human low-density lipoprotein. When and how this antioxidant becomes a pro-oxidant. Biochem J 1992;288(Pt 2):341–344.Google Scholar
  247. 247.
    Thomas SR, Stocker R. Molecular action of vitamin E in lipoprotein oxidation: implications for atherosclerosis. Free Radic Biol Med 2000;28(12):1795–1805.PubMedCrossRefGoogle Scholar
  248. 248.
    Ziegler D. Clinical trials of -lipoic acid in diabetic polyneuropathy and cardiac autonomic neuropathy. In: Packer L, Rosen P, Tritschler HJ, King GL (Eds). Antioxidants in Diabetes Management. New York: Marcel Decker, 2000, pp. 173–184.Google Scholar
  249. 249.
    UKPDS Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. Br Med J 1998;317(7160):703–713.Google Scholar
  250. 250.
    Writing Team For DCCT/EDIC Research Group. Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) study. JAMA 2003;290(16):2159–2167.CrossRefGoogle Scholar
  251. 251.
    Pedersen TR. Coronary artery disease: the Scandinavian Simvastatin Survival Study experience. Am J Cardiol 1998;82(10B):53T–56T.Google Scholar
  252. 252.
    Tomas M, Senti M, Garcia-Faria F, Vila J, Torrents A, Covas M, Marrugat J. Effect of simvastatin therapy on PON activity and related lipoproteins in familial hypercholesterolemic patients. Arterioscler Thromb Vasc Biol 2000;20:2113–2119.PubMedGoogle Scholar
  253. 253.
    De Caterina R, Cipollone F, Filardo FP, Zimarino M, Bernini W, Lazzerini G, Bucciarelli T, Falco A, Marchesani P, Muraro R, Mezzetti A, Ciabattoni G. Low-density lipoprotein level reduction by the 3-hydroxy-3-methylglutaryl coenzyme-A inhibitor simvastatin is accompanied by a related reduction of F2-isoprostane formation in hypercholesterolemic subjects: no further effect of vitamin E. Circulation 2002;106(20):2543–2549.PubMedCrossRefGoogle Scholar
  254. 254.
    Albert MA, Danielson E, Rifai N, Ridker PM. Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA 2001;286(1):64–70.PubMedCrossRefGoogle Scholar
  255. 255.
    Wassmann S, Nickenig G. Interrelationship of free oxygen radicals and endothelial dysfunction–modulation by statins. Endothelium 2003;10(1):23–33.PubMedCrossRefGoogle Scholar
  256. 256.
    Bocan TM. Pleiotropic effects of HMG-CoA reductase inhibitors. Curr Opin Investig Drugs 2002;3(9):1312–1317.PubMedGoogle Scholar
  257. 257.
    Tsunekawa T, Hayashi T, Kano H, Sumi D, Matsui-Hirai H, Thakur NK, Egashira K, Iguchi A. Cerivastatin, a hydroxymethylglutaryl coenzyme a reductase inhibitor, improves endothelial function in elderly diabetic patients within 3 days. Circulation 2001;104(4):376–379.PubMedCrossRefGoogle Scholar
  258. 258.
    Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S, RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345(12):861–869.Google Scholar
  259. 259.
    Gumieniczek A. Effect of the new thiazolidinedione-pioglitazone on the development of oxidative stress in liver and kidney of diabetic rabbits. Life Sci 2003;74(5):553–562.PubMedCrossRefGoogle Scholar
  260. 260.
    Mizushige K, Tsuji T, Noma T. Pioglitazone: cardiovascular effects in prediabetic patients. Cardiovasc Drug Rev 2002;20(4):329–340.PubMedGoogle Scholar
  261. 261.
    May JM, Qu ZC. Troglitazone protects human erythrocytes from oxidant damage. Antioxid Redox Signal 2000;2(2):243–250.PubMedCrossRefGoogle Scholar
  262. 262.
    Garg R, Kumbkarni Y, Aljada A, Mohanty P, Ghanim H, Hamouda W, Dandona P. Troglitazone reduces reactive oxygen species generation by leukocytes and lipid peroxidation and improves flow-mediated vasodilatation in obese subjects. Hypertension 2000;36(3): 430–435.PubMedGoogle Scholar
  263. 263.
    Cominacini L, Garbin U, Pasini AF, Davoli A, Campagnola M, Rigoni A, Tosetti L, Lo Cascio V. The expression of adhesion molecules on endothelial cells is inhibited by troglitazone through its antioxidant activity. Cell Adhes Comm 1999;7(3):223–231.CrossRefGoogle Scholar
  264. 264.
    Cominacini L, Young MM, Capriati A, Garbin U, Fratta Pasini A, Campagnola M, Davoli A, Rigoni A, Contessi GB, Lo Cascio V. Troglitazone increases the resistance of low density lipoprotein to oxidation in healthy volunteers. Diabetologia 1997;40(10):1211–1218.PubMedCrossRefGoogle Scholar
  265. 265.
    American Diabetes Association. Position Statement. Standards of medical care in diabetes. Diabetes Care 2004;27(Supp 1):S15–S35.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Alicia J. Jenkins
    • 1
  • Michael A. Hill
    • 2
  • Kevin G. Rowley
    • 3
  1. 1.Department of Medicine, St. Vincent's HospitalThe University of MelbourneFitzroyAustralia
  2. 2.Department of Medical Pharmacology and PhysiologyUniversity of MissouriColumbiaUSA
  3. 3.Onemda VicHealth Koori Health Unit, Centre for Health and SocietyThe University of MelbourneAustralia

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