Predictive power of hematological and biochemical biomarkers in diabetic retinopathy

Year 2025, Volume: 35 Issue: 5, 825 - 837, 28.10.2025

Ahmet Kürşad Sakallıoğlu , Perihan Demircan Ökmen , Ayşe Naz Mutlu Dinç , Ayça Küpeli Çınar , Abdulkadir Can Çinar , Ramazan Birgül , Hande Güçlü

https://doi.org/10.54005/geneltip.1613743

Abstract

Abstract
Background/Aims: Diabetic retinopathy (DR) is estimated to affect 27.0% of individuals with diabetes, resulting in approximately 0.4 million cases of blindness. Identifying novel biomarkers with predictive value could offer a promising approach to enhance the management of diabetic patients Therefore, this study aimed to investigate the efficacy of hematologic and biochemical biomarkers in DR subtypes.
Methods: This retrospective comparative case study was conducted on 111 patients with diabetes mellitus (DM), divided into three equal groups: non-retinopathic diabetes mellitus (NRDM), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). The changes in the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), eosinophil-monocyte ratio (EMR), monocyte-lymphocyte ratio (MLR), systemic immuno-inflammation index (SII), systemic inflammatory response index (SIRI), hematological, and biochemical parameters between the groups were investigated.
Results: No significant difference was found in age, gender, or duration of DM between the groups. NLR, PLR, SII, SIRI, MLR, urea, and creatinine increased significantly with DR progression (P<0.001, P<0.001, P<0.001, P<0.001, P<0.001, P<0.001, P=0.047, P=0.017, respectively). In contrast, lymphocyte, red blood cell counts, hemoglobin, hematocrit, albumin, and direct bilirubin decreased significantly with DR progression (P<0.001, P=0.034, P=0.003, P=0.002, P<0.001, P=0.045, respectively). In ROC analysis, NLR, PLR, SII, SIRI, SIRI, MLR, and neutrophil count values showed good discrimination power with high specificity and sensitivity. In contrast, ROC analysis was not statistically significant, or the area under the curve values were low for other parameters that showed significant differences between groups. In binary logistic regression analysis, NLR, PLR, SII, SIRI, MLRx10, and neutrophil count showed a higher correlation with PDR.
Conclusions: SIRI, NLR, MLR, PLR, and SII values are significantly associated with PDR. The widespread use of these parameters in clinical practice may positively impact the follow-up and management of DR.

Keywords

Diabetes Mellitus , Diabetic Retinopathy , Biomarkers , Inflammation , Neutrophils , Platelet Count , Lymphocyte Count

Diyabetik retinopatide hematolojik ve biyokimyasal biyobelirteçlerin öngörü gücü

Abstract

Giriş/Amaç: Diyabetik retinopatinin (DR) diyabetli bireylerin %27,0'ını etkilediği ve yaklaşık 0,4 milyon körlük vakasına yol açtığı tahmin edilmektedir. Öngörücü değeri olan yeni biyobelirteçlerin tanımlanması, diyabetik hastaların yönetimini geliştirmek için umut verici bir yaklaşım sunabilir Bu nedenle, bu çalışma DR alt tiplerinde hematolojik ve biyokimyasal biyobelirteçlerin etkinliğini araştırmayı amaçlamıştır.
Gereçler ve Yöntem: Bu retrospektif karşılaştırmalı vaka çalışması, retinopatik olmayan diyabetes mellitus (NRDM), proliferatif olmayan diyabetik retinopati (NPDR) ve proliferatif diyabetik retinopati (PDR) olmak üzere üç eşit gruba ayrılmış 111 diyabetli hastada yürütülmüştür. Gruplar arasında nötrofil-lenfosit oranı (NLR), trombosit-lenfosit oranı (PLR), eozinofil-monosit oranı (EMR), monosit-lenfosit oranı (MLR), sistemik immüno-inflamasyon indeksi (SII), sistemik inflamatuar yanıt indeksi (SIRI), hematolojik ve biyokimyasal parametrelerdeki değişiklikler araştırılmıştır.
Bulgular: Gruplar arasında yaş, cinsiyet veya DM süresi açısından anlamlı bir fark bulunmamıştır. NLR, PLR, SII, SIRI, MLR, üre ve kreatinin DR progresyonu ile birlikte anlamlı şekilde artmıştır (sırasıyla P<0.001, P<0.001, P<0.001, P<0.001, P<0.001, P<0.001, P=0.047, P=0.017). Buna karşılık, lenfosit, kırmızı kan hücresi sayıları, hemoglobin, hematokrit, albümin ve direkt bilirubin DR progresyonu ile birlikte anlamlı şekilde azalmıştır (sırasıyla P<0.001, P=0.034, P=0.003, P=0.002, P<0.001, P=0.045). ROC analizinde NLR, PLR, SII, SIRI, SIRI, MLR ve nötrofil sayısı değerleri yüksek özgüllük ve duyarlılıkla birlikte iyi bir ayrım gücü gösterdi. Buna karşılık, gruplar arasında anlamlı farklılıklar gösteren diğer parametreler için ROC analizi istatistiksel olarak anlamlı değildi veya eğri altındaki alan değerleri düşüktü. İkili lojistik regresyon analizinde, NLR, PLR, SII, SIRI, MLRx10 ve nötrofil sayısı PDR ile daha yüksek bir korelasyon gösterdi.
Sonuç: SIRI, NLR, MLR, PLR ve SII değerleri PDR ile anlamlı şekilde ilişkilidir. Bu parametrelerin klinik uygulamada yaygın kullanımı DR'nin takibini ve yönetimini olumlu etkileyebilir.

Keywords

Diyabet Mellitus , Diyabetik Retinopati , Biyobelirteçler , İnflamasyon , Nötrofiller , Trombosit Sayısı , Lenfosit Sayısı

References

• 1. Ong KL, Stafford LK, McLaughlin SA, Boyko EJ, Vollset SE, Smith AE, et al. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 2023;402(10397):203–34.
• 2. Faselis C, Katsimardou A, Imprialos K, Deligkaris P, Kallistratos M, Dimitriadis K. Microvascular complications of type 2 diabetes mellitus. Curr Vasc Pharmacol 2020;18(2):117–24.
• 3. Crasto W, Patel V, Davies MJ, Khunti, K. Prevention of microvascular complications of diabetes. Endocrinology and Metabolism Clinics 2021;50(3), 431-55.
• 4. Zegeye AF, Temachu YZ, Mekonnen CK. Prevalence and factors associated with Diabetes retinopathy among type 2 diabetic patients at Northwest Amhara Comprehensive Specialized Hospitals, Northwest Ethiopia 2021. BMC Ophthalmol 2023;23(1):9.
• 5. Curran K, Piyasena P, Congdon N, Duke L, Malanda B, Peto T. Inclusion of diabetic retinopathy screening strategies in national-level diabetes care planning in low-and middle-income countries: a scoping review. Heal Res Policy Syst 2023;21(1):2.
• 6. Dascalu AM, Serban D, Tanasescu D, Vancea G, Cristea BM, Stana D, et al. The value of white cell inflammatory biomarkers as potential predictors for diabetic retinopathy in type 2 diabetes mellitus (T2DM). Biomedicines 2023;11(8):2106.
• 7. Usalp S. Does the eosinophil-to-monocyte ratio predict inflammation in patients with diabetic retinopathy: Diabetic retinopathy and Eosinophil-to-monocyte ratio. Int J Curr Med Biol Sci 2024;4(1):10–4.
• 8. Wang S, Pan X, Jia B, Chen S. Exploring the correlation between the systemic Immune inflammation index (SII), systemic inflammatory response index (SIRI), and type 2 Diabetic Retinopathy. Diabetes, Metab Syndr Obes 2023;3827–36.
• 9. Li J, Wang X, Jia W, Wang K, Wang W, Diao W, et al. Association of the systemic immuno-inflammation index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio with diabetic microvascular complications. Front Endocrinol (Lausanne) 2024;15:1367376.
• 10. Yang S, Berdine G. The receiver operating characteristic (ROC) curve. Southwest Respir Crit Care Chronicles 2017;5(19):34–6.
• 11. Ockrim Z, Yorston D. Managing diabetic retinopathy. Bmj 2010;341:c5400.
• 12. Antonetti DA, Silva PS, Stitt AW. Current understanding of the molecular and cellular pathology of diabetic retinopathy. Nat Rev Endocrinol 2021;17(4):195–206.
• 13. Dascalu AM, Georgescu A, Costea AC, Tribus L, El Youssoufi A, Serban D, et al. Association between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with diabetic retinopathy in type 2 diabetic patients. Cureus 2023;15(11).
• 14. Swathi M, Ramya T, Gangaram U, Kumar KK, Sandeep B. A study of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) with glycosylated hemoglobin (HBA1C) among type 2 diabetic patients. Int J Acad Med Pharm 2023;5(4):2023.
• 15. Mani S, Thirunavukkarasu A. A Clinico-Haematologic Study of Diabetic Retinopathy. tnoa J Ophthalmic Sci Res 2023;61(3):317–22.
• 16. Hussain M, Babar MZM, Akhtar L, Hussain MS. Neutrophil lymphocyte ratio (NLR): A well assessment tool of glycemic control in type 2 diabetic patients. Pakistan J Med Sci 2017;33(6):1366.
• 17. Eissa MS, Abou-ElEzz S, Kanzel SM, Mady M. Neutrophil-lymphocyte ratio and its relation to microvascular complication in geriatric patients with diabetes: a case-controlled study. Egypt J Intern Med 2022;34(1):94.
• 18. Maloney S, Pavlakis N, Itchins M, Arena J, Mittal A, Hudson A, et al. The prognostic and predictive role of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) as biomarkers in resected pancreatic cancer. J Clin Med 2023;12(5):1989. 19. Radulescu D, Baleanu VD, Padureanu V, Radulescu PM, Bordu S, Patrascu S, et al. Neutrophil/lymphocyte ratio as predictor of anastomotic leak after gastric cancer surgery. Diagnostics 2020;10(10):799.
• 20. Rajendrakumar AL, Hapca SM, Nair ATN, Huang Y, Chourasia MK, Kwan RS-Y, et al. Competing risks analysis for neutrophil to lymphocyte ratio as a predictor of diabetic retinopathy incidence in the Scottish population. BMC Med 2023;21(1):304.
• 21. El-Tawab SS, Ibrahim IK, Megallaa MH, Mgeed RMA, Elemary WS. Neutrophil–lymphocyte ratio as a reliable marker to predict pre-clinical retinopathy among type 2 diabetic patients. Egypt Rheumatol Rehabil 2023;50(1):11.
• 22. Lei C, Gu J, Liu L, Zhang K, Zhang M. The correlation between peripheral complete blood count parameters and diabetic macular edema in proliferative diabetic retinopathy patients: a cross-sectional study. Front Endocrinol (Lausanne) 2023;14:1190239.
• 23. Lee M-K, Han K-D, Lee J-H, Sohn S-Y, Jeong J-S, Kim M-K, et al. High hemoglobin levels are associated with decreased risk of diabetic retinopathy in Korean type 2 diabetes. Sci Rep 2018;8(1):5538.
• 24. Traveset A, Rubinat E, Ortega E, Alcubierre N, Vazquez B, Hernández M, et al. Lower hemoglobin concentration is associated with retinal ischemia and the severity of diabetic retinopathy in type 2 diabetes. J Diabetes Res 2016;2016(1):3674946.
• 25. Liu MY, Xie YS, Dong ZY, Zhang XG, Sun XF, Zhang D. The role of hemoglobin in differentiating diabetic nephropathy from non-diabetic renal disease. Chin J Kidney Dis Invest (Electr, Chin) 2018;7:271–6.
• 26. Chen X, Zhao J, You Y, Li Z, Chen S. The ratio of fibrinogen to albumin is related to the occurrence of retinopathy in type 2 diabetic patients. Diabetes, Metab Syndr Obes 2023;1859–67.