Nonlinear relationship between serum ferritin and diabetic retinopathy in patients with type 2 diabetes mellitus: mediating role of neutrophil-to-albumin ratio

Aims To clarify the relationship between serum ferritin (SF) levels and diabetic retinopathy (DR) and to analyze the mediating role of the neutrophil-to-albumin ratio (NAR). Methods A total of 1,884 middle-aged and elderly patients (aged ≥ 45 years) with type 2 diabetes mellitus (T2DM) were included in this study. Participants were divided into non-DR and DR groups. Adjusted regression models, receiver operating characteristic (ROC) curve analysis, threshold effect analysis, and mediation effect analysis were performed. T2DM patients were divided into three groups, and differences in the prevalence of DR were compared. Results SF and NAR levels were higher in the DR group than in the non-DR group (P < 0.05). Logistic regression analysis showed a significant positive correlation between SF levels and the risk of DR. Restricted cubic spline (RCS) and threshold effect analyses revealed a nonlinear relationship between SF and the risk of DR, with an optimal inflection point at a SF value of 27.9556. Additionally, NAR was positively correlated with the risk of DR. The prevalence of DR increased with increasing levels of NAR markers and SF ( P < 0.05). Mediation analysis of the association between NAR and the risk of DR showed that the total effect estimate was 0.0003, the direct effect estimate was 0.0003, and the mediation effect estimate was 0.0001, with the mediation proportion accounting for 20.99% of the total effect. The combination of SF and NAR demonstrated potential as an indicator for DR, with an area under the ROC curve (AUC) of 0.69. Conclusions SF levels in middle-aged and elderly patients with T2DM are associated with an increased risk of DR. NAR, an inflammatory marker, plays an important mediating role in the association between ferritin and the risk of DR. The combined use of SF and NAR may serve as a more sensitive indicator for the early diagnosis of DR.