Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Association between haemoglobin levels and the risk of diabetic retinopathy in adults with type 2 diabetes: a retrospective cohort study using the TriNetX network

Eye volume 39, pages 2822–2829 (2025)Cite this article

Subjects

Abstract

Background

Diabetic retinopathy (DR) is the leading cause of preventable blindness. Although hyperglycaemia is the primary driver, other modifiable risk factors may contribute to DR development. This study investigated the association between haemoglobin levels and DR risk in adults with type 2 diabetes.

Methods

We conducted a retrospective cohort study using the TriNetX network (2010–2022). Adults aged ≥45 years with type 2 diabetes were divided into low haemoglobin (LHB, 8–12 g/dL) and control (≥12 g/dL) groups. Propensity score matching was used to address potential confounders. The primary outcome was new-onset DR occurring 6–36 months after the index date. The secondary outcomes included DR subtypes and diabetic ophthalmic complications. Subgroup analyses examined effect modifications by hypertension status, glycaemic control, and sex.

Results

After propensity score matching (28,882 patients per group), patients in the LHB group showed significantly higher risk of overall DR (HR: 1.33, 95% CI: 1.24–1.44), proliferative DR (HR: 1.95, 95% CI: 1.62–2.35), and non-proliferative DR (HR: 1.19, 95% CI: 1.06–1.33). Even mild haemoglobin reductions (10–12 g/dL) were associated with increased DR risk. The association was stronger in patients without hypertension (HR: 1.58 vs 1.21), remained consistent regardless of HbA1c levels, and was more pronounced in males than females.

Conclusion

Low haemoglobin levels independently increased the risk of DR in adults with type 2 diabetes, with the strongest association for proliferative DR. Routine haemoglobin monitoring and maintenance of optimal levels may represent a modifiable risk factor for DR prevention along with glycaemic control and blood pressure management.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Study timeline and patient selection flowchart.

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the TriNetX Research Network, but restrictions apply to the availability of these data, which were used under a collaboration agreement for the current study, and so are not publicly available. Data are available from the corresponding author (Kuo-Chuan Hung) upon reasonable request and with permission from TriNetX. Access to de-identified data requires either TriNetX network membership or establishment of a collaborative agreement with TriNetX.

References

  1. Kropp M, Golubnitschaja O, Mazurakova A, Koklesova L, Sargheini N, Vo T-TKS, et al. Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications—risks and mitigation. EPMA J. 2023;14:21–42.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Steinmetz JD, Bourne RRA, Briant PS, Flaxman SR, Taylor HRB, Jonas JB, et al. Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study. Lancet Glob Health. 2021;9:e144–e60.

    Article  Google Scholar 

  3. Teo ZL, Tham Y-C, Yu M, Chee ML, Rim TH, Cheung N, et al. Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis. Ophthalmology. 2021;128:1580–91.

    Article  PubMed  Google Scholar 

  4. Ting DSW, Cheung GCM, Wong TY. Diabetic retinopathy: global prevalence, major risk factors, screening practices and public health challenges: a review. Clin Exp Ophthalmol. 2016;44:260–77.

    Article  PubMed  Google Scholar 

  5. Bek T. Systemic risk factors contribute differently to the development of proliferative diabetic retinopathy and clinically significant macular oedema. Diabetologia. 2020;63:2462–70.

    Article  CAS  PubMed  Google Scholar 

  6. Sakko S, Karpale M, Tapio J, Leppänen I, Ahokas O, Saarela V, et al. Hemoglobin levels are associated with retinal vascular caliber in a middle-aged birth cohort. Sci Rep. 2024;14:9092.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Zhuang X, Cao D, Zeng Y, Yang D, Yao J, Kuang J, et al. Associations between retinal microvasculature/microstructure and renal function in type 2 diabetes patients with early chronic kidney disease. Diabetes Res Clin Pr. 2020;168:108373.

    Article  CAS  Google Scholar 

  8. Ghamdi AHA. Clinical predictors of diabetic retinopathy progression; a systematic review. Curr Diabetes Rev. 2020;16:242–7.

    PubMed  Google Scholar 

  9. Shinojima A, Lee D, Tsubota K, Negishi K, Kurihara T. Retinal diseases regulated by hypoxia—basic and clinical perspectives: a comprehensive review. J Clin Med. 2021;10:5496.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Li Y, Yu Y, VanderBeek BL. Anaemia and the risk of progression from non-proliferative diabetic retinopathy to vision threatening diabetic retinopathy. Eye. 2020;34:934–41.

    Article  CAS  PubMed  Google Scholar 

  11. Taderegew MM, Tewodros G, Abera TA, Woldeamanuel GG. Anemia and its associated factors among type 2 diabetes mellitus patients attending Debre Berhan referral hospital, North-East Ethiopia: a cross-sectional study. J Blood Med. 2020;11:47–58.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Faghir-Ganji M, Abdolmohammadi N, Nikbina M, Amanollahi A, Ansari-Moghaddam A, Rozhan R, et al. Prevalence of anemia in patients with diabetes mellitus: a systematic review and meta-analysis. Biomed Environ Sci. 2024;37:96–107.

    PubMed  Google Scholar 

  13. Li X, Chen M. Correlation of hemoglobin levels with diabetic retinopathy in US adults aged ≥40 years: the NHANES 2005–2008. Front Endocrinol. 2023;14:1195647.

    Article  Google Scholar 

  14. Wang J, Xin X, Luo W, Wang R, Wang X, Si S, et al. Anemia and diabetic kidney disease had joint effect on diabetic retinopathy among patients with type 2 diabetes. Invest Ophthalmol Vis Sci. 2020;61:25.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. AlFalasi SM, Abdouli KA, Aldashti NA. Association of anemia and diabetic retinopathy among patients with type 2 diabetes mellitus: retrospective cross-sectional study. Cureus. 2024;16:e67995.

    PubMed Central  PubMed  Google Scholar 

  16. Dziedziak J, Zaleska-Żmijewska A, Szaflik JP, Cudnoch-Jędrzejewska A. Impact of arterial hypertension on the eye: a review of the pathogenesis, diagnostic methods, and treatment of hypertensive retinopathy. Med Sci Monit. 2022;28:e935135.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Liu L, Quang ND, Banu R, Kumar H, Tham Y-C, Cheng C-Y, et al. Hypertension, blood pressure control and diabetic retinopathy in a large population-based study. PLOS One. 2020;15:e0229665.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Liu Y, Li J, Ma J, Tong N. The threshold of the severity of diabetic retinopathy below which intensive glycemic control is beneficial in diabetic patients: estimation using data from large randomized clinical trials. J Diabetes Res. 2020;2020:8765139.

    PubMed Central  PubMed  Google Scholar 

  19. Shiferaw WS, Akalu TY, Desta M, Kassie AM, Petrucka PM, Assefa HK, et al. Glycated hemoglobin A1C level and the risk of diabetic retinopathy in Africa: a systematic review and meta-analysis. Diabetes Metab Syndr. 2020;14:1941–9.

    Article  PubMed  Google Scholar 

  20. Park JY, Hwang JH, Kang MJ, Sim HE, Kim JS, Ko KS. Effects of glycemic variability on the progression of diabetic retinopathy among patients with type 2 diabetes. Retina. 2021;41:1487–95.

    Article  CAS  PubMed  Google Scholar 

  21. Wermine K, Gotewal S, Song J, Huang LG, Corona KK, Chokshi SN, et al. Patterns of antibiotic administration in patients with burn injuries: a TriNetX study. Burns. 2024;50:52–8.

    Article  PubMed  Google Scholar 

  22. Hoskins M, Sefick S, Zurca AD, Walter V, Thomas NJ, Krawiec C. Current utilization of interosseous access in pediatrics: a population-based analysis using an EHR database, TriNetX. Int J Emerg Med. 2022;15:65.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Yendewa GA, Olasehinde T, Mulindwa F, Salata RA, Mohareb AM, Jacobson JM. Chronic hepatitis B and COVID-19 clinical outcomes in the United States: a multisite retrospective cohort study. Open Forum Infect Dis. 2025;12:ofaf013.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Ho CN, Sun CK, Wu JY, Chen JY, Chang YJ, Chen IW, et al. Association of vitamin D deficiency with post-stroke depression: a retrospective cohort study from the TriNetX US collaborative networks. Front Nutr. 2023;10:1236233.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Chen IW, Yu TS, Lai YC, Yang CP, Yu CH, Hung KC. Association between vitamin D deficiency and clinical outcome in patients with COVID-19 in the post-Omicron phase. Front Nutr. 2025;12:1583276.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Min J, Zeng T, Roux M, Lazar D, Chen L, Tudzarova S. The role of HIF1α-PFKFB3 pathway in diabetic retinopathy. J Clin Endocrinol Metab. 2021;106:2505–19.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Han N, Xu H, Yu N, Wu Y, Yu L. MiR-203a-3p inhibits retinal angiogenesis and alleviates proliferative diabetic retinopathy in oxygen-induced retinopathy (OIR) rat model via targeting VEGFA and HIF-1α. Clin Exp Pharm Physiol. 2020;47:85–94.

    Article  CAS  Google Scholar 

  28. Atef MM, Shafik NM, Mostafa HY, Mohamed WM, Amal S, Shafik HM, et al. The evolving role of long noncoding RNA HIF1A-AS2 in diabetic retinopathy: a cross-link axis between hypoxia, oxidative stress and angiogenesis via MAPK/VEGF-dependent pathway. Redox Rep. 2022;27:70–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Yang J, Liu Z. Mechanistic pathogenesis of endothelial dysfunction in diabetic nephropathy and retinopathy. Front Endocrinol. 2022;13:816400.

    Article  Google Scholar 

  30. Theuerle JD, Al-Fiadh AH, Amirul Islam FM, Patel SK, Burrell LM, Wong TY, et al. Impaired retinal microvascular function predicts long-term adverse events in patients with cardiovascular disease. Cardiovasc Res. 2020;117:1949–57.

    Article  Google Scholar 

  31. Del Pinto R, Mulè G, Vadalà M, Carollo C, Cottone S, Agabiti Rosei C, et al. Arterial hypertension and the hidden disease of the eye: diagnostic tools and therapeutic strategies. Nutrients. 2022;14:2200.

    Article  PubMed Central  PubMed  Google Scholar 

  32. Takahashi T, Iwasaki A. Sex differences in immune responses. Science. 2021;371:347–8.

    Article  CAS  PubMed  Google Scholar 

  33. Bradshaw JL, Vasini B, Mabry S, Hefley BS, Wilson EN, Gardner JJ, et al. Chronic intermittent hypoxia modulates corneal fibrotic markers and inflammatory cytokine expression in a sex-dependent manner. Exp Eye Res. 2025;255:110358.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Chi Mei Medical Center, Tainan city, Taiwan

    Kuo-Chuan Hung, Ying-Jen Chang & Ming Yew

  2. School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung city, Taiwan

    Kuo-Chuan Hung

  3. Department of Anesthesiology, E-Da Hospital, I-Shou University, Kaohsiung city, Taiwan

    Li-Chen Chang

  4. Department of Recreation and Health-Care Management, College of Recreation and Health Management, Chia Nan University of Pharmacy and Science, Tainan City, Taiwan

    Ying-Jen Chang

  5. Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung city, Taiwan

    Chih-Wei Hsu

  6. Department of Nutrition, Chi Mei Medical Center, Tainan City, Taiwan

    Jheng-Yan Wu

  7. Department of Anesthesiology, Chi Mei Medical Center, Liouying, Tainan city, Taiwan

    I-Wen Chen

Authors
  1. Kuo-Chuan Hung
    View author publications

    Search author on:PubMed Google Scholar

  2. Li-Chen Chang
    View author publications

    Search author on:PubMed Google Scholar

  3. Ying-Jen Chang
    View author publications

    Search author on:PubMed Google Scholar

  4. Chih-Wei Hsu
    View author publications

    Search author on:PubMed Google Scholar

  5. Ming Yew
    View author publications

    Search author on:PubMed Google Scholar

  6. Jheng-Yan Wu
    View author publications

    Search author on:PubMed Google Scholar

  7. I-Wen Chen
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Kuo-Chuan Hung and Li-Chen Chang: Conceptualisation, Methodology, Software; Ying-Jen Chang and Chih-Wei Hsu: Data curation; Ming Yew and I-Wen Chen: Visualisation, Investigation; Jheng-Yan Wu: Supervision; I-Wen Chen: Software, Validation; Kuo-Chuan Hung and I-Wen Chen: Writing- Original draft preparation; Kuo-Chuan Hung and I-Wen Chen: Writing- Reviewing and Editing.

Corresponding author

Correspondence to I-Wen Chen.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval

The use of TriNetX in this study was approved by the Institutional Review Board of Chi Mei Medical Center (No. 11403-E01).

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hung, KC., Chang, LC., Chang, YJ. et al. Association between haemoglobin levels and the risk of diabetic retinopathy in adults with type 2 diabetes: a retrospective cohort study using the TriNetX network. Eye 39, 2822–2829 (2025). https://doi.org/10.1038/s41433-025-03982-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41433-025-03982-0

Search

Advanced search

Quick links