FAS and the risk of diabetic retinopathy in patients with type 2 diabetes mellitus

Background Chronic inflammation is considered to play an important role in the development and progression of diabetic retinopathy (DR). In this study, we investigated the predictive value of a score constructed from fibrinogen and albumin for DR risk and identified individuals with well-controlled glycated hemoglobin A1c (HbA1c) who remain at high risk of DR. Methods Discovery and validation cohorts, which included 715 patients with type 2 diabetes mellitus (T2DM), were enrolled in the study. Peripheral biomarkers (platelets, neutrophils, monocytes, lymphocytes, fibrinogen, albumin, and HbA1c) were detected, and we investigated the predictive value and risk-stratified roles of 10 inflammatory biomarkers in the two cohorts. Results In the discovery cohort, neutrophil-to-lymphocyte ratio (NLR), fibrinogen-to-albumin ratio (FAR), and fibrinogen-to-albumin score (FAS) were significantly associated with the risk of DR, and FAS showed the highest discriminatory ability. The predictive performance of FAS for DR, in terms of area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was 0.69, 0.83, 0.43, 0.42, and 0.83 in the discovery cohort, and 0.69, 0.82, 0.42, 0.47, and 0.77 in the validation cohort, respectively. When FAS was added to a base model, the resulting model (model 4) achieved an AUC of 0.80 in the discovery cohort and 0.76 in the validation cohort. Model 4 showed good calibration and high net benefit, and net reclassification improvement (NRI)/integrated discrimination improvement (IDI) analyses confirmed the incremental predictive value of FAS. Subgroup analyses by age, estimated glomerular filtration rate (eGFR), hypertension, and insulin therapy showed no significant interactions, indicating that FAS is a robust predictive biomarker across these subgroups. When stratified by HbA1c, patients with low FAS and well-controlled HbA1c had the lowest DR rate, whereas those with a FAS score of 2 had the highest DR rates. Conclusion FAS is a robust and independent predictive biomarker for DR, with consistent performance across subgroups, including in patients with well-controlled HbA1c.