Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Diabetes Reviews
  4. Fast Track Articles
  5. Fast Track Article
image of An Association between Bilirubin and Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus: An Effect Modification by Nrf2 Polymorphisms
file format pdf download PDF

Abstract

Background

iabetic retinopathy (DR) is a persistent microvascular complication associated with diabetes, and it constitutes a significant cause of visual impairment and blindness.

Aims

This study aimed to assess the correlation between serum bilirubin levels and the prevalence of DR in patients diagnosed with type 2 diabetes mellitus (T2DM). Additionally, we sought to establish whether the polymorphisms of Nuclear Factor E2-Related Factor 2 (Nrf2) might modify this relationship.

Methods

A cross-sectional study was undertaken in Jiangxi, China, from May, 2012 to December, 2014. Serum bilirubin levels were assessed in 558 subjects, and the correlation between bilirubin and DR was analyzed using generalized linear models with a logit link. The study utilized odds ratios (OR) and 95% confidence intervals (CI) to evaluate the relationship, both with and without the consideration of clinical risk factors.

Results

There was a significant inverse association between serum total bilirubin (TBiL) and the risk of DR (per 1-μmol/L increment; OR, 0.89; 95% CI: 0.84-0.94). Accordingly, when TBiL was categorized into tertiles, individuals in tertiles 2 and 3 exhibited significantly lower risks of DR compared to those in tertile 1. The OR for these tertiles was 0.54 (95% CI: 0.34-0.87) and 0.31 (95% CI: 0.19-0.52), respectively. Moreover, a stronger inverse relationship between TBiL and DR was observed in individuals carrying the CC and AC genotypes compared to those with the AA genotype. The OR for individuals with the CC/AC genotype was 0.87 (95% CI: 0.82, 0.92), while that for the AA genotype was 1.17 (95% CI: 0.95, 1.45). This difference was statistically significant ( for interaction = 0.001).

Conclusion

There was a significant inverse association between bilirubin and DR in participants with CC or AC genotype. However, this inverse association was not seen in AA genotype participants.

© 2024 The Author(s). Published by Bentham Science Publishers
© 2024 The Author(s). Published by Bentham Science Publishers. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode.
Loading

Article metrics loading...

/content/journals/cdr/10.2174/0115733998327164240923070313
2024-11-29
2025-01-22

  • From This Site

    /content/journals/cdr/10.2174/0115733998327164240923070313
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

/deliver/fulltext/cdr/10.2174/0115733998327164240923070313/BMS-CDR-2024-90.html?itemId=/content/journals/cdr/10.2174/0115733998327164240923070313&mimeType=html&fmt=ahah

References

  1. Sun H. Saeedi P. Karuranga S. Pinkepank M. Ogurtsova K. Duncan B.B. Stein C. Basit A. Chan J.C.N. Mbanya J.C. Pavkov M.E. Ramachandaran A. Wild S.H. James S. Herman W.H. Zhang P. Bommer C. Kuo S. Boyko E.J. Magliano D.J. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res. Clin. Pract. 2022 183 109119 10.1016/j.diabres.2021.109119 34879977
    [Google Scholar]
  2. Bommer C. Heesemann E. Sagalova V. Manne-Goehler J. Atun R. Bärnighausen T. Vollmer S. The global economic burden of diabetes in adults aged 20–79 years: A cost-of-illness study. Lancet Diabetes Endocrinol. 2017 5 6 423 430 10.1016/S2213‑8587(17)30097‑9 28456416
    [Google Scholar]
  3. Curran K. Peto T. Jonas J.B. Friedman D. Kim J.E. Leasher J. Tapply I. Fernandes A.G. Cicinelli M.V. Arrigo A. Leveziel N. Resnikoff S. Taylor H.R. Sedighi T. Flaxman S. Bikbov M.M. Braithwaite T. Bron A. Cheng C-Y. Del Monte M.A. Ehrlich J.R. Furtado J.M. Gazzard G. Hartnett M.E. Kahloun R. Kempen J.H. Khairallah M. Khanna R.C. Lansingh V.C. Naidoo K.S. Nangia V. Nowak M. Pesudovs K. Ramulu P. Topouzis F. Tsilimbaris M. Wang Y.X. Wang N. Bourne R.R.A. Curran K. Peto T. Bourne R. Leasher J.L. Jonas J.B. Friedman D.S. Kim J.E. Fernandes A.G. Ahinkorah B.O. Ahmadieh H. Ahmed A. Alfaar A.S. Almidani L. Amu H. Androudi S. Arabloo J. Aravkin A.Y. Asemu M.T. Azzam A.Y. Baghcheghi N. Bailey F. Baran M.F. Bardhan M. Bärnighausen T.W. Barrow A. Bhardwaj P. Bikbov M. Braithwaite T. Briant P.S. Burkart K. Cámera L.A. Coberly K. Dadras O. Dai X. Dehghan A. Demessa B.H. Diress M. Do T.C. Do T.H.P. Dokova K.G. Duncan B.B. Ekholuenetale M. Elhadi M. Emamian M.H. Emamverdi M. Farrokhpour H. Fatehizadeh A. Desideri L.F. Furtado J.M. Gebrehiwot M. Ghassemi F. Gudeta M.D. Gupta S. Gupta V.B. Gupta V.K. Hammond B.R. Harorani M. Hasani H. Heidari G. Hosseinzadeh M. Huang J.J. Islam S.M.S. Javadi N. Jimenez-Corona A. Jokar M. Joshua C.E. Kadashetti V. Kandel H. Kasraei H. Kaur R.J. Khanal S. Khorrami Z. Koohestani H.R. Krishan K. Lim S.S. El Razek M.M.A. Mansouri V. Maugeri A. Mestrovic T. Misganaw A. Mokdad A.H. Momeni-Moghaddam H. Momtazmanesh S. Murray C.J.L. Negash H. Osuagwu U.L. Pardhan S. Patel J. Pawar S. Petcu I-R. Pham H.T. Pourazizi M. Qattea I. Rahman M. Saeed U. Sahebkar A. Salehi M.A. Shayan M. Shittu A. Steinmetz J.D. Tan Y. Topouzis F. Tsatsakis A. Umair M. Vos T. Xiao H. You Y. Zastrozhin M.S. Zhang Z-J. Zheng P. Vision Loss Expert Group of the Global Burden of Disease Study GBD 2019 Blindness and Vision Impairment Collaborators Global estimates on the number of people blind or visually impaired by diabetic retinopathy: A meta-analysis from 2000 to 2020. Eye. 2024 38 11 2047 2057 10.1038/s41433‑024‑03101‑5 38937557
    [Google Scholar]
  4. Hussain A. Ashique S. Afzal O. Altamimi M.A. Malik A. Kumar S. Garg A. Sharma N. Farid A. Khan T. Altamimi A.S.A. A correlation between oxidative stress and diabetic retinopathy: An updated review. Exp. Eye Res. 2023 236 109650 10.1016/j.exer.2023.109650 37734426
    [Google Scholar]
  5. Kang Q. Yang C. Oxidative stress and diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications. Redox Biol. 2020 37 101799 10.1016/j.redox.2020.101799 33248932
    [Google Scholar]
  6. Tian S. Yang X. Lin Y. Li X. Zhou S. Yu P. Zhao Y. PDK4-mediated Nrf2 inactivation contributes to oxidative stress and diabetic kidney injury. Cell. Signal. 2024 121 111282 10.1016/j.cellsig.2024.111282 38971568
    [Google Scholar]
  7. Dahiya R. Walia A. Kaur J. Kumar P. Verma I. Rani N. Diabetic retinopathy - Pathophysiology to treatment: A review. Curr. Diabetes Rev. 2024 20 10.2174/0115733998259940231105200251 38315658
    [Google Scholar]
  8. Dennery P.A. Weng Y.H. Stevenson D.K. Yang G. The biology of bilirubin production. J. Perinatol. 2001 21 S1 Suppl. 1 S17 S20 10.1038/sj.jp.7210627 11803410
    [Google Scholar]
  9. Al-Suhaimi E.A. Al-Rubaish A.A. Interplay of serum biomarkers bilirubin and γ-glutamyltranspeptidase in predicting cardiovascular complications in type-2 diabetes mellitus. World J. Diabetes 2024 15 6 1074 1078 10.4239/wjd.v15.i6.1074 38983815
    [Google Scholar]
  10. Zuo L. Huang J. Zhang H. Huang B. Wu X. Chen L. Xia S. Dong X. Hao G. Dose-response association between bilirubin and cardiovascular disease: A systematic review and meta-analysis. Angiology 2022 73 10 911 919 10.1177/00033197211059693 35015578
    [Google Scholar]
  11. Moss K. Dennis B.B. Naji L. Ahmed A. Kim D. Total bilirubin levels in nonalcoholic fatty liver disease and all-cause and cause-specific mortality in US adults. J. Gastrointestin. Liver Dis. 2023 32 3 323 331 10.15403/jgld‑4732 37774224
    [Google Scholar]
  12. Wang J. Wang B. Liang M. Wang G. Li JP J. Zhang Y. Huo Y. Cui Y. Xu X. Qin X. Independent and combined effect of bilirubin and smoking on the progression of chronic kidney disease. Clin. Epidemiol. 2018 10 121 132 10.2147/CLEP.S150687 29391834
    [Google Scholar]
  13. Wang J. Zhang X. Zhang Z. Zhang Y. Zhang J. Li H. Li Y. Wang B. Nie J. Liang M. Wang G. Cai Y. Li J. Zhang Y. Huo Y. Cui Y. Xu X. Qin X. Baseline serum bilirubin and risk of first stroke in hypertensive patients. J. Am. Heart Assoc. 2020 9 12 e015799 10.1161/JAHA.119.015799 32486877
    [Google Scholar]
  14. Lu Y. Sun Y. Liu Z. Lu Y. Zhu X. Lan B. Mi Z. Dang L. Li N. Zhan W. Tan L. Pi J. Xiong H. Zhang L. Chen Y. Activation of NRF2 ameliorates oxidative stress and cystogenesis in autosomal dominant polycystic kidney disease. Sci. Transl. Med. 2020 12 554 eaba3613 10.1126/scitranslmed.aba3613 32727915
    [Google Scholar]
  15. Sorour N.E. Abd El-Kareem H.M. Ibrahim A.E. Salem R.M. Nuclear factor erythroid-2-related factor 2 gene polymorphisms in vitiligo. J. Clin. Aesthet. Dermatol. 2021 14 6 14 17 34804349
    [Google Scholar]
  16. Wang X. Chen H. Liu J. Ouyang Y. Wang D. Bao W. Liu L. Association between the NF-E2 related factor 2 gene polymorphism and oxidative stress, anti-oxidative status, and newly-diagnosed type 2 diabetes mellitus in a Chinese population. Int. J. Mol. Sci. 2015 16 7 16483 16496 10.3390/ijms160716483 26204833
    [Google Scholar]
  17. Hu Y. Wang J. Zeng S. Chen M. Zou G. Li Y. Zhu L. Xu J. Association between serum albumin levels and diabetic peripheral neuropathy among patients with type 2 diabetes: Effect modification of body mass index. Diabetes Metab. Syndr. Obes. 2022 15 527 534 10.2147/DMSO.S347349 35228809
    [Google Scholar]
  18. Alberti K.G.M.M. Zimmet P.Z. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus. Provisional report of a WHO Consultation. Diabet. Med. 1998 15 7 539 553 10.1002/(SICI)1096‑9136(199807)15:7<539::AID‑DIA668>3.0.CO;2‑S 9686693
    [Google Scholar]
  19. Shultz K.S. Whitney D.J. Zickar M.J. Measurement theory in action: Case studies and exercises. 2nd ed New York Routledge 2013 35 37 10.4324/9781315869834
    [Google Scholar]
  20. Su Z. Liu W. Yang J. Association between proliferative diabetic retinopathy and serum bile acid level in patients with type 2 diabetes mellitus. Endocr. Metab. Immune Disord. Drug Targets 2021 21 11 2063 2067 10.2174/1871530321666210112160724 33438572
    [Google Scholar]
  21. Kudo K. Inoue T. Sonoda N. Ogawa Y. Inoguchi T. Relationship between serum bilirubin levels, urinary biopyrrin levels, and retinopathy in patients with diabetes. PLoS One 2021 16 2 e0243407 10.1371/journal.pone.0243407 33571217
    [Google Scholar]
  22. Liu M. Wang J. He Y. The U-Shaped Association between bilirubin and diabetic retinopathy risk: A five-year cohort based on 5323 male diabetic patients. J. Diabetes Res. 2018 2018 1 7 10.1155/2018/4603087 30510963
    [Google Scholar]
  23. Huang E.J. Kuo W.W. Chen Y.J. Chen T.H. Chang M.H. Lu M.C. Tzang B.S. Hsu H.H. Huang C.Y. Lee S.D. Homocysteine and other biochemical parameters in Type 2 diabetes mellitus with different diabetic duration or diabetic retinopathy. Clin. Chim. Acta 2006 366 1-2 293 298 10.1016/j.cca.2005.10.025 16343469
    [Google Scholar]
  24. Hajam Y.A. Rani R. Ganie S.Y. Sheikh T.A. Javaid D. Qadri S.S. Pramodh S. Alsulimani A. Alkhanani M.F. Harakeh S. Hussain A. Haque S. Reshi M.S. Oxidative stress in human pathology and aging: Molecular mechanisms and perspectives. Cells 2022 11 3 552 10.3390/cells11030552 35159361
    [Google Scholar]
  25. Volpe C.M.O. Villar-Delfino P.H. dos Anjos P.M.F. Nogueira-Machado J.A. Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell Death Dis. 2018 9 2 119 10.1038/s41419‑017‑0135‑z 29371661
    [Google Scholar]
  26. Wang J.C. Zhao Y. Chen S.J. Long J. Jia Q.Q. Zhai J.D. Zhang Q. Chen Y. Long H.B. AOPPs induce MCP-1 expression by increasing ROS-mediated activation of the NF-κB pathway in rat mesangial cells: Inhibition by sesquiterpene lactones. Cell. Physiol. Biochem. 2013 32 6 1867 1877 10.1159/000356619 24356300
    [Google Scholar]
  27. Mahajan N. Arora P. Sandhir R. Perturbed biochemical pathways and associated oxidative stress lead to vascular dysfunctions in diabetic retinopathy. Oxid. Med. Cell. Longev. 2019 2019 1 16 10.1155/2019/8458472 30962865
    [Google Scholar]
  28. Kowluru R.A. Effect of reinstitution of good glycemic control on retinal oxidative stress and nitrative stress in diabetic rats. Diabetes 2003 52 3 818 823 10.2337/diabetes.52.3.818 12606525
    [Google Scholar]
  29. Stocker R. Yamamoto Y. McDonagh A.F. Glazer A.N. Ames B.N. Bilirubin is an antioxidant of possible physiological importance. Science 1987 235 4792 1043 1046 10.1126/science.3029864 3029864
    [Google Scholar]
  30. Punzo A. Silla A. Fogacci F. Perillo M. Cicero A.F.G. Caliceti C. Bile acids and bilirubin role in oxidative stress and inflammation in cardiovascular diseases. Diseases 2024 12 5 103 10.3390/diseases12050103 38785758
    [Google Scholar]
  31. Suzuki T. Shibata T. Takaya K. Shiraishi K. Kohno T. Kunitoh H. Tsuta K. Furuta K. Goto K. Hosoda F. Sakamoto H. Motohashi H. Yamamoto M. Regulatory nexus of synthesis and degradation deciphers cellular Nrf2 expression levels. Mol. Cell. Biol. 2013 33 12 2402 2412 10.1128/MCB.00065‑13 23572560
    [Google Scholar]
  32. Wang Y. Fu X. Zeng L. Hu Y. Gao R. Xian S. Liao S. Huang J. Yang Y. Liu J. Jin H. Klaunig J. Lu Y. Zhou S. Activation of Nrf2/HO-1 signaling pathway exacerbates cholestatic liver injury. Commun. Biol. 2024 7 1 621 10.1038/s42003‑024‑06243‑0 38783088
    [Google Scholar]
  33. He F. Ru X. Wen T. NRF2, a transcription factor for stress response and beyond. Int. J. Mol. Sci. 2020 21 13 4777 10.3390/ijms21134777 32640524
    [Google Scholar]
  34. Alcaraz M.J. Ferrándiz M.L. Relevance of Nrf2 and heme oxygenase-1 in articular diseases. Free Radic. Biol. Med. 2020 157 83 93 10.1016/j.freeradbiomed.2019.12.007 31830562
    [Google Scholar]
/content/journals/cdr/10.2174/0115733998327164240923070313
Loading
An Association between Bilirubin and Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus: An Effect Modification by Nrf2 Polymorphisms
Bentham Science Publishers ; https://doi.org/10.2174/0115733998327164240923070313
/content/journals/cdr/10.2174/0115733998327164240923070313
/content/journals/cdr/10.2174/0115733998327164240923070313
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

file format download Download

  • Article Type:     Research Article
Keywords: diabetic retinopathy ; total bilirubin ; Nrf2 polymorphisms ; antioxidant ; diabetic mellitus ; Serum bilirubin

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test