Increased Fatty Acid-Binding Protein 4 levels are associated with the Risk of Developing Retinopathy in Type 2 Diabetes Mellitus Patients - 18/04/25

Doi : 10.1016/j.diabet.2025.101653

Yan Liu ^1,^{^{#
Yan Liu and Kaihui Ma contributed equally to this paper.}}, Kaihui Ma ^2,^3,^{^{#
Yan Liu and Kaihui Ma contributed equally to this paper.}}, Aiying Zhang ¹, Yun Cui ¹, Hui Zhao ^2,³, Xinhua Li ^2,^3,^⁎ , Ke Zhao ^2,^3,^4,^⁎
¹ Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
² Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
³ Shandong Institute of Endocrine & Metabolic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
⁴ Jinan Key Laboratory of Translational Medicine on Metabolic Diseases, Jinan, China

^⁎Corresponding author: Xinhua Li, Professor, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, 18877 Jingshi road, Jinan, ChinaEndocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences18877 Jingshi roadJinanChina^⁎⁎Corresponding author: Ke Zhao, Professor, Jinan Key Laboratory of Translational Medicine on Metabolic Diseases, 18877 Jingshi road, Jinan 250062, ChinaJinan Key Laboratory of Translational Medicine on Metabolic Diseases18877 Jingshi roadJinan250062China

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Abstract

Aim

Fatty acid-binding protein 4 (FABP4) is associated with the risk of developing diabetes and its microvascular complications. We aimed to explore the association between serum FABP4 levels and the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).

Methods

Serum FABP4 levels were measured via enzyme-linked immunosorbent assay in 275 individuals (78 healthy controls, 197 T2DM patients). DR severity was determined via fundus fluorescence angiography. Multivariate analyses were performed via logistic regression models. The diagnostic value of these measures was assessed via receiver operating characteristic curve analysis.

Results

Serum FABP4 levels were significantly greater in the proliferative DR (PDR) group than in the ZeroDR (ZDR) and non-proliferative DR (NPDR) groups, and the FABP4 levels positively with DR severity (r = 0.328, P < 0.001). Logistic regression analysis revealed that after adjusting for potential confounders, increased FABP4, fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) levels were risk factors for DR development, and FABP4 was an independent risk factor for PDR development. A multivariate logistic regression model that included FABP4 as a categorical binary variable with a cutoff value of 20.57 ng/ml revealed that a level of FABP4 above the cutoff value increased the DR risk (OR=6.394; 95% CI=3.18;13.58; P < 0.001). Similarly, a FABP4 concentration above the cutoff value of 24.40 ng/ml increased the PDR risk (OR=4.686; 95% CI=1.907;12.34; P = 0.001).

Conclusion

The FABP4 level is associated with DR severity and has the potential as a serum biomarker for DR prediction.

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Keywords : Biomarker, Diabetic retinopathy, Fatty acid-binding protein 4, Type 2 diabetes mellitus

Abbreviations : DR, DM, NPDR, PDR, BRB, VEGF, FABP4, IR, T2DM, BMI, ZDR, SBP, DBP, FPG, TG, TCHO, HDL-c, LDL-c, Hs-CRP, HbA1c, FINS, HOMA-IR, HOMA-β, ELISA, ROC, AUC, OR, CI, TNF-α, IL, PPAR, NF-κB, MMP, OIR, CNV, ER