Nutrition Research and Practice

  • 제18권4호
  • /
  • Pages.511-522
  • /
  • 2024
  • /
  • 1976-1457(pISSN)
  • /
  • 2005-6168(eISSN)
한국영양학회 (The Korean Nutrition Society)
권호 표지
DOI QR코드

DOI QR Code

Homocysteine levels are associated with diabetes mellitus in Chinese with H-type hypertension

  • Dejian Fu (Department of Cardiovascular, The People's Hospital of Zigui County) ;
  • Wanbao Gong (Department of Cardiovascular, Changyang Tujia Autonomous County People's Hospital) ;
  • Xiaomin Bao (Department of Cardiovascular, People's Hospital of Huantai County) ;
  • Bo Yang (Department of Cardiovascular, The People's Hospital of Wufeng Tujia Autonomous County) ;
  • Feng Wang (Clinical laboratory, The People's Hospital of Wufeng Tujia Autonomous County) ;
  • Yubing Qiao (Department of Cardiovascular, Zigui County Hospital of Traditional Chinese Medicine) ;
  • Yuanjiang Wu (Clinical laboratory, Zigui County Hospital of Traditional Chinese Medicine) ;
  • Guangzhen Chen (Department of Cardiovascular, The People's Hospital of Wufeng Tujia Autonomous County) ;
  • Weixun Sun (Clinical laboratory, Changyang Tujia Autonomous County People's Hospital) ;
  • Qiongzhi Xiao (Department of Cardiovascular, The People's Hospital of Wufeng Tujia Autonomous County) ;
  • Wenbo Zou (Department of Cardiovascular, Yidu Hospital of Traditional Chinese Medicine) ;
  • Ning Fang (Department of Cardiovascular, Changyang Tujia Autonomous County People's Hospital)
  • 투고 : 2022.10.13
  • 심사 : 2024.04.15
  • 발행 : 2024.08.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

BACKGROUND/OBJECTIVES: The study examined the association between homocysteine and diabetes mellitus in patients with H-type hypertension and assessed the possible effect modifiers. SUBJECTS/METHODS: This cross-sectional study included 1,255 eligible participants in the 'H-type Hypertension Management and Stroke Prevention Strategic International Science and Technology Innovation Cooperation Project' among rural Chinese people with H-type hypertension. A multivariate logistic regression model was used to evaluate the relationship between homocysteine and diabetes mellitus. RESULTS: The mean level of total homocysteine (tHcy) in the diabetes mellitus population was 19.37 μmol/L, which was significantly higher than the non-diabetic patients (18.18 μmol/L). When tHcy was analyzed as a continuous variable, the odds ratio (OR) of diabetes was 1.17 (95% confidence interval [CI], 1.01-1.35; per interquartile range). When tHcy was stratified according to the quintile, the ORs for diabetes were 2.86 (95% CI, 1.22-6.69) in the highest quintile (tHcy ≥ 20.60 μmol/L) compared to the reference group (tHcy < 12.04 μmol/L). When tHcy was grouped by 15 μmol/L and 20 μmol/L, patients with tHcy ≥ 20 μmol/L had a significantly (P = 0.037) higher risk of diabetes (OR, 2.03; 95% CI, 1.04-3.96) than in those with tHcy < 15 μmol/L. Subgroup analysis showed that the tHcy-diabetes association was unaffected by other variables. CONCLUSION: In this study of rural Chinese people with H-type hypertension, the tHcy levels showed a positive association with diabetes mellitus. This independent association is unaffected by other potential risk factors.

키워드

과제정보

We thank all the participants for their important contributions. In particular, we would like to acknowledge the lead units for this study, Peking University First Hospital and The Second Affiliated Hospital of Nanchang University.

참고문헌

  1. Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet 2017;389:2239-51. https://doi.org/10.1016/S0140-6736(17)30058-2
  2. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995;274:1049-57. https://doi.org/10.1001/jama.1995.03530130055028
  3. Verhoef P, Stampfer MJ, Buring JE, Gaziano JM, Allen RH, Stabler SP, Reynolds RD, Kok FJ, Hennekens CH, Willett WC. Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate. Am J Epidemiol 1996;143:845-59. https://doi.org/10.1093/oxfordjournals.aje.a008828
  4. Emoto M, Kanda H, Shoji T, Kawagishi T, Komatsu M, Mori K, Tahara H, Ishimura E, Inaba M, Okuno Y, et al. Impact of insulin resistance and nephropathy on homocysteine in type 2 diabetes. Diabetes Care 2001;24:533-8. https://doi.org/10.2337/diacare.24.3.533
  5. Hoogeveen EK, Kostense PJ, Beks PJ, Mackaay AJ, Jakobs C, Bouter LM, Heine RJ, Stehouwer CD. 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. https://doi.org/10.1161/01.ATV.18.1.133
  6. Ala OA, Akintunde AA, Ikem RT, Kolawole BA, Ala OO, Adedeji TA. Association between insulin resistance and total plasma homocysteine levels in type 2 diabetes mellitus patients in south west Nigeria. Diabetes Metab Syndr 2017;11 Suppl 2:S803-9. https://doi.org/10.1016/j.dsx.2017.06.002
  7. Ndrepepa G, Kastrati A, Braun S, Koch W, Kolling K, Mehilli J, Schomig A. Circulating homocysteine levels in patients with type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis 2008;18:66-73. https://doi.org/10.1016/j.numecd.2006.03.007
  8. Passaro A, D'Elia K, Pareschi PL, Calzoni F, Carantoni M, Fellin R, Solini A. Factors influencing plasma homocysteine levels in type 2 diabetes. Diabetes Care 2000;23:420-1. https://doi.org/10.2337/diacare.23.3.420
  9. Yu C, Wang J, Wang F, Han X, Hu H, Yuan J, Miao X, Yao P, Wei S, Wang Y, et al. Inverse association between plasma homocysteine concentrations and type 2 diabetes mellitus among a middle-aged and elderly Chinese population. Nutr Metab Cardiovasc Dis 2018;28:278-84. https://doi.org/10.1016/j.numecd.2017.11.009
  10. Executive summary: standards of medical care in diabetes--2010. Diabetes Care 2010;33 Suppl 1:S4-10. https://doi.org/10.2337/dc10-S004
  11. Ebesunun MO, Obajobi EO. Elevated plasma homocysteine in type 2 diabetes mellitus: a risk factor for cardiovascular diseases. Pan Afr Med J 2012;12:48.
  12. Yuan X, Ding S, Zhou L, Wen S, Du A, Diao J. Association between plasma homocysteine levels and pancreatic islet beta-cell function in the patients with type 2 diabetes mellitus: a cross-sectional study from China. Ann Palliat Med 2021;10:8169-79. https://doi.org/10.21037/apm-21-1671
  13. Schaffer A, Verdoia M, Barbieri L, Cassetti E, Suryapranata H, De Luca G. Impact of diabetes on homocysteine levels and its relationship with coronary artery disease: a single-centre cohort study. Ann Nutr Metab 2016;68:180-8.  https://doi.org/10.1159/000441478
  14. Platt DE, Hariri E, Salameh P, Merhi M, Sabbah N, Helou M, Mouzaya F, Nemer R, Al-Sarraj Y, El-Shanti H, et al. Type II diabetes mellitus and hyperhomocysteinemia: a complex interaction. Diabetol Metab Syndr 2017;9:19.
  15. Wang YS, Ye J, Yang X, Zhang GP, Cao YH, Zhang R, Dai W, Zhang Q. Association of retinol binding protein-4, cystatin C, homocysteine and high-sensitivity C-reactive protein levels in patients with newly diagnosed type 2 diabetes mellitus. Arch Med Sci 2019;15:1203-16. https://doi.org/10.5114/aoms.2018.79565
  16. Qin X, Li Y, Yuan H, Xie D, Tang G, Wang B, Wang X, Xu X, Xu X, Hou F. Relationship of MTHFR gene 677C → T polymorphism, homocysteine, and estimated glomerular filtration rate levels with the risk of new-onset diabetes. Medicine (Baltimore) 2015;94:e563.
  17. Smulders YM, Rakic M, Slaats EH, Treskes M, Sijbrands EJ, Odekerken DA, Stehouwer CD, Silberbusch J. Fasting and post-methionine homocysteine levels in NIDDM. Determinants and correlations with retinopathy, albuminuria, and cardiovascular disease. Diabetes Care 1999;22:125-32. https://doi.org/10.2337/diacare.22.1.125
  18. 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. https://doi.org/10.2337/diacare.23.12.1816
  19. Koehler KM, Baumgartner RN, Garry PJ, Allen RH, Stabler SP, Rimm EB. Association of folate intake and serum homocysteine in elderly persons according to vitamin supplementation and alcohol use. Am J Clin Nutr 2001;73:628-37. https://doi.org/10.1093/ajcn/73.3.628
  20. Stickel F, Choi SW, Kim YI, Bagley PJ, Seitz HK, Russell RM, Selhub J, Mason JB. Effect of chronic alcohol consumption on total plasma homocysteine level in rats. Alcohol Clin Exp Res 2000;24:259-64. https://doi.org/10.1111/j.1530-0277.2000.tb04606.x
  21. Russo GT, Di Benedetto A, Giorda C, Alessi E, Crisafulli G, Ientile R, Di Cesare E, Jacques PF, Raimondo G, Cucinotta D. Correlates of total homocysteine plasma concentration in type 2 diabetes. Eur J Clin Invest 2004;34:197-204. https://doi.org/10.1111/j.1365-2362.2004.01319.x
  22. Wang B, Wu H, Li Y, Ban Q, Huang X, Chen L, Li J, Zhang Y, Cui Y, He M, et al. Effect of long-term low-dose folic acid supplementation on degree of total homocysteine-lowering: major effect modifiers. Br J Nutr 2018;120:1122-30. https://doi.org/10.1017/S0007114518002477
  23. Refsum H, Smith AD, Ueland PM, Nexo E, Clarke R, McPartlin J, Johnston C, Engbaek F, Schneede J, McPartlin C, et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem 2004;50:3-32. https://doi.org/10.1373/clinchem.2003.021634
  24. Thogersen AM, Nilsson TK, Dahlen G, Jansson JH, Boman K, Huhtasaari F, Hallmans G. Homozygosity for the C677-->T mutation of 5,10-methylenetetrahydrofolate reductase and total plasma homocyst(e) ine are not associated with greater than normal risk of a first myocardial infarction in northern Sweden. Coron Artery Dis 2001;12:85-90. https://doi.org/10.1097/00019501-200103000-00001
  25. Friedman G, Goldschmidt N, Friedlander Y, Ben-Yehuda A, Selhub J, Babaey S, Mendel M, Kidron M, Bar-On H. A common mutation A1298C in human methylenetetrahydrofolate reductase gene: association with plasma total homocysteine and folate concentrations. J Nutr 1999;129:1656-61. https://doi.org/10.1093/jn/129.9.1656
  26. Stampfer MJ, Grodstein F. Can homocysteine be related to physical functioning? Am J Med 2002;113:610-1. https://doi.org/10.1016/S0002-9343(02)01352-9
  27. Han L, Liu Y, Wang C, Tang L, Feng X, Astell-Burt T, Wen Q, Duan D, Lu N, Xu G, et al. Determinants of hyperhomocysteinemia in healthy and hypertensive subjects: a population-based study and systematic review. Clin Nutr 2017;36:1215-30. https://doi.org/10.1016/j.clnu.2016.11.011
  28. Challa F, Getahun T, Sileshi M, Nigassie B, Geto Z, Ashibire G, Gelibo T, Teferra S, Seifu D, Sitotaw Y, et al. Prevalence of hyperhomocysteinaemia and associated factors among Ethiopian adult population in a 2015 national survey. BioMed Res Int 2020;2020:9210261.
  29. Zeng Q, Li F, Xiang T, Wang W, Ma C, Yang C, Chen H, Xiang H. Influence of food groups on plasma total homocysteine for specific MTHFR C677T genotypes in Chinese population. Mol Nutr Food Res 2017;61:1600351.
  30. Shi C, Wang P, Airen S, Brown C, Liu Z, Townsend JH, Wang J, Jiang H. Nutritional and medical food therapies for diabetic retinopathy. Eye Vis (Lond) 2020;7:33.
  31. Selhub J, Jacques PF, Rosenberg IH, Rogers G, Bowman BA, Gunter EW, Wright JD, Johnson CL. Serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey (1991-1994): population reference ranges and contribution of vitamin status to high serum concentrations. Ann Intern Med 1999;131:331-9. https://doi.org/10.7326/0003-4819-131-5-199909070-00003
  32. Brattstrom L. Vitamins as homocysteine-lowering agents. J Nutr 1996;126:1276S-80S. https://doi.org/10.1093/jn/126.suppl_4.1276S
  33. Jacob RA, Wu MM, Henning SM, Swendseid ME. Homocysteine increases as folate decreases in plasma of healthy men during short-term dietary folate and methyl group restriction. J Nutr 1994;124:1072-80. https://doi.org/10.1093/jn/124.7.1072
  34. Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 1993;270:2693-8. https://doi.org/10.1001/jama.1993.03510220049033
  35. Aydemir O, Turkcuoglu P, Guler M, Celiker U, Ustundag B, Yilmaz T, Metin K. Plasma and vitreous homocysteine concentrations in patients with proliferative diabetic retinopathy. Retina 2008;28:741-3. https://doi.org/10.1097/IAE.0b013e31816079fb
  36. Wang T, Wang Q, Wang Z, Xiao Z, Liu L. Diagnostic value of the combined measurement of serum Hcy, serum Cys C, and urinary microalbumin in type 2 diabetes mellitus with early complicating diabetic nephropathy. ISRN Endocrinol 2013;2013:407452.
  37. Zheng LQ, Zhang HL, Guan ZH, Hu MY, Zhang T, Ge SJ. Elevated serum homocysteine level in the development of diabetic peripheral neuropathy. Genet Mol Res 2015;14:15365-75. https://doi.org/10.4238/2015.November.30.14
  38. Hermans MP, Gala JL, Buysschaert M. The MTHFR CT polymorphism confers a high risk for stroke in both homozygous and heterozygous T allele carriers with type 2 diabetes. Diabet Med 2006;23:529-36. https://doi.org/10.1111/j.1464-5491.2006.01841.x
  39. Ostrakhovitch EA, Tabibzadeh S. Homocysteine and age-associated disorders. Ageing Res Rev 2019;49:144-64. https://doi.org/10.1016/j.arr.2018.10.010
  40. Shin JY. Trends in the prevalence and management of diabetes in Korea: 2007-2017. Epidemiol Health 2019;41:e2019029.
  41. Xu R, Huang F, Wang Y, Liu Q, Lv Y, Zhang Q. Gender- and age-related differences in homocysteine concentration: a cross-sectional study of the general population of China. Sci Rep 2020;10:17401.
  42. Blom HJ. Determinants of plasma homocysteine. Am J Clin Nutr 1998;67:188-9. https://doi.org/10.1093/ajcn/67.2.188
  43. Choi SH, Choi-Kwon S, Kim MS, Kim JS. Poor nutrition and alcohol consumption are related to high serum homocysteine level at post-stroke. Nutr Res Pract 2015;9:503-10. https://doi.org/10.4162/nrp.2015.9.5.503
  44. Hornemann T. Serine deficiency causes complications in diabetes. Nature 2023;614:42-3.
  45. Yang M, Vousden KH. Serine and one-carbon metabolism in cancer. Nat Rev Cancer 2016;16:650-62. https://doi.org/10.1038/nrc.2016.81
  46. Davis SR, Stacpoole PW, Williamson J, Kick LS, Quinlivan EP, Coats BS, Shane B, Bailey LB, Gregory JF 3rd. Tracer-derived total and folate-dependent homocysteine remethylation and synthesis rates in humans indicate that serine is the main one-carbon donor. Am J Physiol Endocrinol Metab 2004;286:E272-9. https://doi.org/10.1152/ajpendo.00351.2003
  47. Cole JB, Florez JC. Genetics of diabetes mellitus and diabetes complications. Nat Rev Nephrol 2020;16:377-90. https://doi.org/10.1038/s41581-020-0278-5
  48. Morrish NJ, Wang SL, Stevens LK, Fuller JH, Keen H. Mortality and causes of death in the WHO multinational study of vascular disease in diabetes. Diabetologia 2001;44 Suppl 2:S14-21. https://doi.org/10.1007/PL00002934