Abstract
INTRODUCTION: Diabetic retinopathy (DR), particularly proliferative diabetic retinopathy (PDR), is a leading cause of blindness. This study aimed to evaluate the predictive value of hemoglobin (Hb) and direct bilirubin (DBil) for PDR progression. METHODS: We retrospectively collected data from 1,496 T2DM patients with DR treated at the South District of the First People's Hospital of Hefei. Logistic regression, correlation analysis, restricted cubic spline models, and Mendelian randomization were used. RESULTS: For each unit increase in Hb and DBil, the risk of PDR decreased by 4.4% and 29.1%, respectively. Restricted cubic spline analyses showed a non-linear association between Hb and PDR: the risk decreased with increasing Hb up to a turning point at approximately 133 g/L and then plateaued thereafter; a turning point of 2.67 µmol/L was identified for DBil. The combined diagnostic model of Hb and DBil yielded an AUC of 0.742 with sensitivity 54.5% and specificity 86.5%, indicating moderate discriminative ability. Subgroup analysis showed higher PDR prevalence with worsening anemia. Mendelian randomization suggested a possible association between genetically predicted anemia and higher PDR risk (OR 1.06, 95% CI 1.003-1.12). CONCLUSION: Lower Hb and DBil levels were associated with higher PDR prevalence in this hospitalized population. These findings reflect statistical associations and require confirmation in prospective, population-based studies.