Homocysteine and vascular disease in diabetes: a double hit?

References

1. Yudkin JS. How can we best prolong life? Benefits of coronary risk factor reduction in non-diabetic and diabetic subjects. Br Med J 1993; 306:1313–8.10.1136/bmj.306.6888.1313Search in Google Scholar

2. Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature 2001; 414:782–7.10.1038/414782aSearch in Google Scholar

3. Grundy SM, Howard B, Smith S Jr, Eckel R, Redberg R, Bonow RO. Prevention Conference VI: Diabetes and Cardiovascular Disease: executive summary: conference proceeding for healthcare professionals from a special writing group of the American Heart Association. Circulation 2002; 105:2231–9.10.1161/01.CIR.0000013952.86046.DDSearch in Google Scholar

4. Eikelboom JW, Lonn E, Genest J, Hankey G, Yusuf S. Homocyst(e)ine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med 1999; 131:363–75.10.7326/0003-4819-131-5-199909070-00008Search in Google Scholar

5. Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. J Am Med Assoc 2002;288:2015–22.10.1001/jama.288.16.2015Search in Google Scholar

6. Toborek M, Kopiecczna-Grzebieniak E, Drozdz M, Wieczorek M. Induced lipid peroxidation as a mechanism of methionine-induced atherosclerosis in rabbits. Atherosclerosis 1995; 115:217–24.10.1016/0021-9150(94)05516-LSearch in Google Scholar

7. van Guldener C, Stehouwer CD. Hyperhomocysteinemia, vascular pathology, and endothelial dysfunction. Semin Thromb Hemost 2000; 26:281–9.10.1055/s-2000-8472Search in Google Scholar PubMed

8. Brattstrom L, Wilcken DE, Ohrvik J, Brudin L. Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: the result of a meta-analysis. Circulation 1998; 98:2520–6.10.1161/01.CIR.98.23.2520Search in Google Scholar

9. Nygard O, Refsum H, Ueland PM, Hollset SG. Major lifestyle determinants of plasma total homocysteine distribution: the Hordaland Homocysteine Study. Am J Clin Nutr 1998; 67:263–70.10.1093/ajcn/67.2.263Search in Google Scholar PubMed

10. Jacques PF, Bostom AG, Wilson PW, Rich S, Rosenberg IH, Selhub J. Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort. Am J Clin Nutr 2001; 73:613–21.10.1093/ajcn/73.3.613Search in Google Scholar PubMed

11. van Guldener C, Stam F, Stehouwer CD. Homocysteine metabolism in renal failure. Kidney Int 2001; 59(Suppl 78):S234–7.10.1046/j.1523-1755.2001.07859.xSearch in Google Scholar

12. Smulders YM, Rakic M, Slaats EH, Treskes M, Sijbrands EJ, Odekerken DA, et al. Fasting and post-methionine homocysteine levels in NIDDM. Determinants and correlations with retinopathy, albuminuria, and cardiovascular disease. Diabetes Care 1999; 22:125–32.10.2337/diacare.22.1.125Search in Google Scholar

13. Stabler SP, Estacio R, Jeffers BW, Cohen JA, Allen RH, Schrier RW. Total homocysteine is associated with nephropathy in non-insulin-dependent diabetes mellitus. Metabolism 1999; 48:1096–101.10.1016/S0026-0495(99)90121-XSearch in Google Scholar

14. Mazza A, Motti C, Nulli A, Marra G, Masso A, Pastore A, et al. Lack of association between carotid intima-media thickness and methylenetetrahydrofolate reductase gene polymorphism or serum homocysteine in non-insulin-dependent diabetes mellitus. Metabolism 2000; 49:718–23.10.1053/meta.2000.6254Search in Google Scholar PubMed

15. Pavia C, Ferrer I, Valls C, Artuch R, Colome C, Vilaseca MA. Total homocysteine in patients with type 1 diabetes. Diabetes Care 2000; 23:84–7.10.2337/diacare.23.1.84Search in Google Scholar PubMed

16. Targher G, Bertolini L, Zenari L, Cacciatori V, Muggeo M, Faccini G, et al. Cigarette smoking and plasma total homocysteine levels in young adults with type 1 diabetes. Diabetes Care 2000; 23:524–8.10.2337/diacare.23.4.524Search in Google Scholar PubMed

17. Emoto M, Kanda H, Shoji T, Kawagishi T, Komatsu M, Mori K, et al. Impact of insulin resistance and nephropathy on homocysteine in type 2 diabetes. Diabetes Care 2001; 24:533–8.10.2337/diacare.24.3.533Search in Google Scholar PubMed

18. Wollesen F, Brattstrom L, Refsum H, Ueland PM, Berglund L, Berne C. Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus. Kidney Int 1999; 55:1028–35.10.1046/j.1523-1755.1999.0550031028.xSearch in Google Scholar PubMed

19. Veldman BA, Vervoort G, Blom H, Smits P. Reduced plasma total homocysteine concentrations in type 1 diabetes mellitus is determined by increased renal clearance. Diabet Med 2005; 22:301–5.10.1111/j.1464-5491.2005.01415.xSearch in Google Scholar PubMed

20. van Guldener C, Donker AJ, Jakobs C, Teerlink T, de Meer K, Stehouwer CD. No net renal extraction of homocysteine in fasting humans. Kidney Int 1998; 54:166–9.10.1046/j.1523-1755.1998.00983.xSearch in Google Scholar PubMed

21. Jacobs RL, House JD, Brosnan ME, Brosnan JT. Effects of streptozotocin-induced diabetes and of insulin treatment on homocysteine metabolism in the rat. Diabetes 1998; 47:1967–70.10.2337/diabetes.47.12.1967Search in Google Scholar

22. Ratnam S, Maclean KN, Jacobs RL, Brosnan ME, Kraus JP, Brosnan JT. Hormonal regulation of cystathionine beta-synthase expression in liver. J Biol Chem 2002; 277:42912–8.10.1074/jbc.M206588200Search in Google Scholar

23. Nieman KM, Rowling MJ, Garrow TA, Schalinske KL. Modulation of methyl group metabolism by streptozotocin-induced diabetes and all-trans-retinoic acid. J Biol Chem 2004; 279:45708–12.10.1074/jbc.M408664200Search in Google Scholar

24. Fonseca VA, Mudaliar S, Schmidt B, Fink LM, Kern PA, Henry RR. Plasma homocysteine concentrations are regulated by acute hyperinsulinemia in nondiabetic but not type 2 diabetic subjects. Metabolism 1998; 47:686–9.10.1016/S0026-0495(98)90031-2Search in Google Scholar

25. Giltay EJ, Hoogeveen EK, Elbers JM, Gooren LJ, Asscheman H, Stehouwer CD. Insulin resistance is associated with elevated plasma total homocysteine levels in healthy, non-obese subjects. Atherosclerosis 1998; 139:197–8.Search in Google Scholar

26. De Pergola G, Pannacciulli N, Zamboni M, Minenna A, Brocco G, Sciaraffia M, et al. Homocysteine plasma levels are independently associated with insulin resistance in normal weight, overweight and obese pre-menopausal women. Diabetes Nutr Metab 2001; 14:253–8.Search in Google Scholar

27. Meigs JB, Jacques PF, Selhub J, Singer DE, Nathan DM, Rifai N, et al. Fasting plasma homocysteine levels in the insulin resistance syndrome: the Framingham offspring study. Diabetes Care 2001; 24:1403–10.10.2337/diacare.24.8.1403Search in Google Scholar

28. Abbasi F, Facchini F, Humphreys MH, Reaven GM. Plasma homocysteine concentrations in healthy volunteers are not related to differences in insulin-mediated glucose disposal. Atherosclerosis 1999; 146:175–8.10.1016/S0021-9150(99)00132-XSearch in Google Scholar

29. Rosolova H, Simon J, Mayer O Jr, Racek J, Dierze T, Jacobsen DW. Unexpected inverse relationship between insulin resistance and serum homocysteine in healthy subjects. Physiol Res 2002; 51:93–8.Search in Google Scholar

30. Godsland IF, Rosankiewicz JR, Proudler AJ, Johnston DG. Plasma total homocysteine concentrations are unrelated to insulin sensitivity and components of the meta-bolic syndrome in healthy men. J Clin Endocrinol Metab 2001; 86:719–23.Search in Google Scholar

31. Buysschaert M, Dramais AS, Wallemacq PE, Hermans MP. Hyperhomocysteinemia in type 2 diabetes: relationship to macroangiopathy, nephropathy, and insulin resistance. Diabetes Care 2000; 23:1816–22.10.2337/diacare.23.12.1816Search in Google Scholar

32. Wiltshire E, Thomas DW, Baghurst P, Couper J. Reduced total plasma homocyst(e)ine in children and adolescents with type 1 diabetes. J Pediatr 2001; 138:888–93.10.1067/mpd.2001.113708Search in Google Scholar

33. Dierkes J, Westphal S, Luley C. Serum homocysteine increases after therapy with fenofibrate or bezafibrate. Lancet 1999; 354:219–20.10.1016/S0140-6736(99)02153-4Search in Google Scholar

34. Cenerelli S, Bonazzi P, Galeazzi R, Testa I, Bonfigli AR, Sirolla C, et al. Helicobacter pylori masks differences in homocysteine plasma levels between controls and type 2 diabetic patients. Eur J Clin Invest 2002; 32:158–62.10.1046/j.1365-2362.2002.00962.xSearch in Google Scholar PubMed

35. Passaro A, D'Elia K, Pareschi PL, Calzoni F, Carantoni M, Fellin R, et al. Factors influencing plasma homocysteine levels in type 2 diabetes. Diabetes Care 2000; 23:420–1.10.2337/diacare.23.3.420Search in Google Scholar

36. Cassone Faldetta M, Laurenti O, Desideri G, Bravi MC, De Luca O, Marinucci MC, et al. L-Arginine infusion decreases plasma total homocysteine concentrations through increased nitric oxide production and decreased oxidative status in type II diabetic patients. Diabetologia 2002; 45:1120–7.10.1007/s00125-002-0854-1Search in Google Scholar

37. Tan KC, Chow WS, Ai VH, Siow YL, Lam KS. Hyperhomocysteinemia and impaired vasomotor function in type 2 diabetes mellitus. Eur J Clin Invest 2002; 32:328–34.10.1046/j.1365-2362.2002.00990.xSearch in Google Scholar

38. Araki A, Sako Y, Ito H. Plasma homocysteine concentrations in Japanese patients with non-insulin-dependent diabetes mellitus: effect of parenteral methylcobalamin treatment. Atherosclerosis 1993; 103:149–57.10.1016/0021-9150(93)90258-VSearch in Google Scholar

39. Chico A, Perez A, Cordoba A, Arcelus R, Carreras G, de Leiva A, et al. Plasma homocysteine is related to albumin excretion rate in patients with diabetes mellitus: a new link between diabetic nephropathy and cardiovascular disease? Diabetologia 1998; 41:684–93.10.1007/s001250050969Search in Google Scholar

40. Hofmann MA, Kohl B, Zumbach MS, Borcea V, Bierhaus A, Henkels M, et al. Hyperhomocyst(e)inemia and endothelial dysfunction in IDDM. Diabetes Care 1998; 21:841–8.10.2337/diacare.21.5.841Search in Google Scholar

41. Mutus B, Rabini RA, Staffolani R, Ricciotti R, Fumelli P, Moretti N, et al. Homocysteine-induced inhibition of nitric oxide production in platelets: a study on healthy and diabetic subjects. Diabetologia 2001; 44:979–82.10.1007/s001250100581Search in Google Scholar

42. Hultberg B, Agardh E, Andersson A, Brattstrom L, Isaksson A, Israelsson B, et al. Increased levels of plasma homocysteine nephropathy, but not severe retinopathy in type 1 diabetes mellitus. Scand J Clin Lab Invest 1991; 51:277–82.10.3109/00365519109091615Search in Google Scholar

43. Lanfredini M, Fiorina P, Peca MG, Veronelli A, Mello A, Astorri E, et al. Fasting and post-methionine load homocyst(e)ine values are correlated with microalbuminuria and could contribute to worsening vascular damage in non-insulin-dependent mellitus patients. Metabolism 1998; 47:915–21.10.1016/S0026-0495(98)90344-4Search in Google Scholar

44. Vaccaro O, Perna AF, Mancini FP, Iovine C, Cuomo V, Sacco M, et al. Plasma homocysteine and microvascular complications in type 1 diabetes. Nutr Metab Cardiovasc Dis 2000; 10:297–304.Search in Google Scholar

45. Robillon JF, Canivet B, Candito M, Sadoul JL, Jullien D, Morand P, et al. Type 1 diabetes mellitus and homocyst(e)ine. Diabetes Metab 1994; 20:494–6.Search in Google Scholar

46. Oishi K, Nagake Y, Yamasaki H, Fukuda S, Ichikawa H, Ota K, et al. The significance of serum homocysteine levels in diabetic patients on haemodialysis. Nephrol Dial Transplant 2000; 15:851–5.10.1093/ndt/15.6.851Search in Google Scholar PubMed

47. Suliman ME, Stenvinkel P, Heimburger O, Barany P, Lindholm B, Bergstrom J, et al. Plasma sulfur amino acids in relation to cardiovascular disease, nutritional status, and diabetes mellitus in patients with chronic renal failure at start of dialysis therapy. Am J Kidney Dis 2002; 40:480–8.10.1053/ajkd.2002.34887Search in Google Scholar

48. Al-Nozah M, Al-Daghri N, Bartlett WA, Al-Attas O, Al-Maatouq M, Martin SC, et al. Serum homocysteine concentration is related to diabetes mellitus, but not to coronary heart disease, in Saudi Arabians. Diabetes Obes Metab 2002; 4:118–23.10.1046/j.1463-1326.2002.00191.xSearch in Google Scholar

49. Cronin CC, McPartlin JM, Barry DG, Ferriss JB, Scott JM, Weir DG, et al. Plasma homocysteine concentrationsin patients with type 1 diabetes. Diabetes Care 1998; 21:1843–7.10.2337/diacare.21.11.1843Search in Google Scholar

50. Kark JD, Selhub J, Bostom A, Adler B, Rosenberg IH. Plasma homocysteine and all-cause mortality in diabetes. Lancet 1999; 353:1936–7.10.1016/S0140-6736(98)05381-1Search in Google Scholar

51. Hoogeveen EK, Kostense PJ, Beks PJ, Mackaay AJ, Jakobs C, Bouter LM, et al. Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin-dependent diabetes mellitus: a population based study. Arterioscler Thromb Vasc Biol 1998; 18:133–8.10.1161/01.ATV.18.1.133Search in Google Scholar

52. Chiarelli F, Pomilio M, Mohn A, Tumini S, Vanelli M, Morgese G, et al. Homocysteine levels during fasting and after methionine loading in adolescents with diabetic retinopathy and nephropathy. J Pediatr 2000; 137:386–92.10.1067/mpd.2000.108103Search in Google Scholar

53. Agardh CD, Agardh E, Andersson A, Hultberg B. Lack of association between plasma homocysteine levels and microangiopathy in type 1 diabetes mellitus. Scand J Clin Lab Invest 1994; 54:637–41.10.3109/00365519409087544Search in Google Scholar

54. Ozmen B, Ozmen D, Turgan N, Habif S, Mutaf I, Bayindir O. Association between homocysteinemia and renal function in patients with type 2 diabetes mellitus. Ann Clin Lab Sci 2002; 32:279–86.Search in Google Scholar

55. Davies L, Wilmshurst EG, McElduff A, Gunton J, Clifton-Bligh P, Fulcher GR. The relationship among homocysteine, creatinine clearance, and albuminuria in patients with type 2 diabetes. Diabetes Care 2001; 24:1805–9.10.2337/diacare.24.10.1805Search in Google Scholar

56. Abdella N, Mojiminiyi OA, Akanji AO. Homocysteine and endogenous markers of renal function in type 2 diabetic patients without coronary heart disease. Diabetes Res Clin Pract 2000; 50:177–85.10.1016/S0168-8227(00)00193-5Search in Google Scholar

57. Hoogeveen EK, Kostense PJ, Jager J, Heine RJ, Jakobs C, Bouter LM, et al. Serum homocysteine level and protein intake are related to risk of albuminuria: the Hoorn Study. Kidney Int 1998; 54:203–9.10.1038/sj.ki.4495353Search in Google Scholar PubMed

58. Jager A, Kostense PJ, Nijpels G, Dekker JM, Heine RJ, Bouter LM, et al. Serum homocysteine levels are associated with the development of (micro)albuminuria: the Hoorn study. Arterioscler Thromb Vasc Biol 2001; 21:74–81.10.1161/01.ATV.21.1.74Search in Google Scholar

59. Hovind P, Tarnow L, Rossing P, Teerlink T, Stehouwer CD, Emeis JJ, et al. Progression of diabetic nephropathy: role of plasma homocysteine and plasminogen activator inhibitor-1. Am J Kidney Dis 2001; 38:1376–80.10.1053/ajkd.2001.29261Search in Google Scholar

60. Klein R, Klein BE, Moss SE, Wang Q. Hypertension and retinopathy, arteriolar narrowing, and arteriovenous nicking in a population. Arch Ophthalmol 1994; 112:92–8.10.1001/archopht.1994.01090130102026Search in Google Scholar

61. Hoogeveen EK, Kostense PJ, Eysink PE, Polak BC, Beks PJ, Jakobs C, et al. Hyperhomocysteinemia is associated with the presence of retinopathy in type 2 diabetesmellitus: the Hoorn Study. Arch Intern Med 2000; 160:2984–90.10.1001/archinte.160.19.2984Search in Google Scholar

62. Hoogeveen EK, Kostense PJ, Valk GD, Bertelsmann FW, Jakobs C, Dekker JM, et al. Hyperhomocysteinaemia is not related to risk of distal somatic polyneuropathy: the Hoorn Study. J Intern Med 1999; 246:561–6.10.1046/j.1365-2796.1999.00566.xSearch in Google Scholar

63. Ambrosch A, Dierkes J, Lobmann R, Kuhne W, Konig W, Luley C, et al. Relation between homocysteinaemia and diabetic neuropathy in patients with type 2 diabetes mellitus. Diabet Med 2001; 18:185–92.10.1046/j.1464-5491.2001.00445.xSearch in Google Scholar

64. Cohen JA, Jeffers BW, Stabler S, Schrier RW, Estascio R. Increasing homocysteine levels and diabetic autonomic neuropathy. Auton Neurosci 2001; 87:268–73.10.1016/S1566-0702(00)00262-9Search in Google Scholar

65. Buysschaert M, Jamart J, Dramais AS, Wallemacq PE, Hermans MP. Micro and macrovascular complications and hyperhomocysteinaemia in type 1 diabetic patients. Diabetes Metab 2001; 27:655–9.Search in Google Scholar

66. Okada E, Oida K, Tada H, Asazuma K, Eguchi K, Tohda G, et al. Hyperhomocysteinemia is a risk factor for coronary arteriosclerosis in Japanese patients with type 2 diabetes. Diabetes Care 1999; 22:484–90.10.2337/diacare.22.3.484Search in Google Scholar PubMed

67. Becker A, Kostense PJ, Bos G, Heine RJ, Dekker JM, Bouter LM, et al. Hyperhomocysteinemia is associated with coronary events in type 2 diabetes. J Intern Med 2003; 253:293–300.10.1046/j.1365-2796.2003.01113.xSearch in Google Scholar PubMed

68. Soinio M, Marniemi J, Laakso M, Lehto S, Ronnemaa T. Elevated plasma homocysteine level is an independent predictor of coronary heart disease events in patients with type 2 diabetes mellitus. Ann Intern Med 2004; 140:94–100.10.7326/0003-4819-140-2-200401200-00009Search in Google Scholar PubMed

69. Durga J, Verhoef P, Bots ML, Schouten E. Homocysteine and carotid intima media thickness; a critical appraisal of the evidence. Atherosclerosis 2004; 176:1–19.10.1016/j.atherosclerosis.2003.11.022Search in Google Scholar

70. Stehouwer CD, Gall MA, Hougaard P, Jacobs C, Parving HH. Plasma homocysteine concentration predicts mortality in non-insulin-dependent diabetic patients with and without albuminuria. Kidney Int 1999; 55:308–14.10.1046/j.1523-1755.1999.00256.xSearch in Google Scholar

71. Hoogeveen EK, Kostense PJ, Jakobs C, Dekker JM, Nijpels G, Heine RJ, et al. Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes: 5-year follow-up of the Hoorn Study. Circulation 2000; 101:1506–11.10.1161/01.CIR.101.13.1506Search in Google Scholar

72. Shukla N, Thompson CS, Angelini GD, Mikhailidis DP, Jeremy J. Homocysteine enhances impairment of endothelium-dependent relaxation and guanosine cyclic monophosphate formation in aortae from diabetic rabbits. Diabetologia 2002; 45:1325–31.10.1007/s00125-002-0888-4Search in Google Scholar

73. West IC. Radicals and oxidative stress in diabetes. Diabet Med 2000; 17:171–80.10.1046/j.1464-5491.2000.00259.xSearch in Google Scholar

74. Jeremy J, Shukla N, Angelini G. Homocysteine and cardiovascular disease in diabetes mellitus. Atherosclerosis 2002; 164:383.10.1016/S0021-9150(02)00066-7Search in Google Scholar

75. Weiss N. Mechanisms of increased vascular oxidant stress in hyperhomocysteinemia and its impact on endothelial function. Curr Drug Metab 2005; 6:27–36.10.2174/1389200052997357Search in Google Scholar PubMed

76. Becker A, Van Hinsbergh VW, Kostense PJ, Jager A, Dekker JM, Nijpels G, et al. Serum homocysteine is weakly associated with von Willebrand factor and soluble vascular cell adhesion molecule 1, but not with C-reactive protein in type 2 diabetic and non-diabetic subjects – the Hoorn Study. Eur J Clin Invest 2000; 30:763–70.10.1046/j.1365-2362.2000.00706.xSearch in Google Scholar PubMed

77. Targher G, Zenari L, Bertolini L, Falezza G, Muggeo M, Zoppini G. Plasma total homocysteine levels are associated with von Willebrand factor, soluble intercellular adhesion molecule-1, and soluble tumor necrosis factor-alpha receptors in young type 1 diabetic patients without clinical evidence of macrovascular complications. Diabetes Care 2001; 24:1496–7.10.2337/diacare.24.8.1496-aSearch in Google Scholar PubMed

78. Jager A, van Hinsbergh VW, Kostense PJ, Emeis JJ, Nijpels G, Dekker JM, et al. Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes: the Hoorn Study. Diabetes 2000; 49:485–91.10.2337/diabetes.49.3.485Search in Google Scholar PubMed

79. Baliga BS, Reynolds T, Fink LM, Fonseca VA. Hyperhomocysteinemia in type 2 diabetes mellitus: cardiovascular risk factors and effect of treatment with folic acid and pyridoxine. Endocrinol Pract 2000; 6:435–41.10.4158/EP.6.6.435Search in Google Scholar

80. Wiltshire EJ, Gent R, Hirte C, Pena A, Thomas DW, Couper JJ. Endothelial dysfunction relates to folate status in children and adolescents with type 1 diabetes. Diabetes 2002; 51:2282–6.10.2337/diabetes.51.7.2282Search in Google Scholar

81. Spijkerman AM, Smulders YM, Kostense PJ, Henry RM, Becker A, Teerlink T, et al. S-Adenosylmethionine and 5-methyltetrahydrofolate are associated with endothelial function after controlling for confounding by homocysteine: the Hoorn Study. Arterioscler Thromb Vasc Biol 2005; 25:778–84.10.1161/01.ATV.0000157981.57694.d2Search in Google Scholar

82. Nygard O, Vollset SE, Refsum H, Stensvold I, Tverdal A, Nordrehaug JE, et al. Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study. J Am Med Assoc 1995; 274:1526–33.10.1001/jama.1995.03530190040032Search in Google Scholar

83. Graham IM, Daly LE, Refsum HM, Stensvold I, Tverdal A, Nordrehaug JE, et al. Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. J Am Med Assoc 1997; 277:1775–81.10.1001/jama.1997.03540460039030Search in Google Scholar

84. Kahleová R, Palyzova D, Zvara K, Zvarova J, Hrach K, Novakova I, et al. Essential hypertension in adolescents: association with insulin resistance and with metabolism of homocysteine and vitamins. Am J Hypertens 2002; 15:857–64.10.1016/S0895-7061(02)02984-9Search in Google Scholar

85. Perna AF, Ingrosso D, De Santo NG, Galletti P, Zappia V. Mechanism of erythrocyte accumulation of methylation inhibitor S-adenosylhomocysteine in uremia. Kidney Int 1995; 47:247–53.10.1038/ki.1995.31Search in Google Scholar

86. Quere I, Perneger TV, Zittoun J, Bellet H, Gris JC, Daures JP, et al. Red blood cell methylfolate and plasma homocysteine as risk factors for venous thromboembolism: a matched case-control study. Lancet 2002; 359:747–52.10.1016/S0140-6736(02)07876-5Search in Google Scholar

87. Loehrer F, Angst C, Brunner F, Haefeli WE, Fowler B. Evidence for disturbed S-adenosylmethionine:S-adenosylhomocysteine ratio in patients with end-stage renal failure: a cause for disturbed methylation reactions? Nephrol Dial Transplant 1998; 13:656–61.10.1093/ndt/13.3.656Search in Google Scholar

88. Lee ME, Wang H. Homocysteine and hypomethylation. A novel link to vascular disease. Trends Cardiovasc Med 1999; 9:49–54.10.1016/S1050-1738(99)00002-XSearch in Google Scholar

89. Dayal S, Bottiglieri T, Arning E, Maeda N, Malinow MR, Sigmund CD, et al. Endothelial dysfunction and elevation of S-adenosylhomocysteine in cystathionine beta-synthase-deficient mice. Circ Res 2001; 88:1203–9.10.1161/hh1101.092180Search in Google Scholar

90. Kerins DM, Koury MJ, Capdevila A, Rana S, Wagner C. Plasma S-adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine. Am J Clin Nutr 2001; 74:723–9.10.1093/ajcn/74.6.723Search in Google Scholar

91. Loehrer FM, Tschopl M, Angst CP, Lytinski P, Jager K, Fowler B, et al. Disturbed ratio of erythrocyte and plasma S-adenosylmethionine/S-adenosylhomocysteine in peripheral arterial occlusive disease. Atherosclerosis 2001; 154:147–54.10.1016/S0021-9150(00)00449-4Search in Google Scholar

92. Poirier LA, Brown AT, Fink LM, Wise CK, Randolph CJ, Delongchamp RR, et al. Blood S-adenosylmethionine concentrations and lymphocyte methylenetetrahydrofolate reductase activity in diabetes mellitus and diabetic nephropathy. Metabolism 2001; 50:1014–8.10.1053/meta.2001.25655Search in Google Scholar PubMed