Association of hemoglobin-to-red cell distribution width ratio with diabetic retinopathy risk and severity

Background Diabetic retinopathy (DR) is a leading cause of blindness in diabetic patients, driven by inflammation, oxidative stress, and hypoxia. The hemoglobin-to-red cell distribution width ratio (HRR) is a novel inflammatory marker reflecting these pathological mechanisms. This study aimed to investigated the association of HRR with DR risk and severity. Methods Data from the 2005–2008 National Health and Nutrition Examination Survey were analyzed using weighted logistic regression, subgroup analysis, restricted cubic splines, mediation analysis, and other methods. Results Among 1,260 diabetic patients, HRR was inversely associated with DR development (OR = 0.85, P = 0.008), remaining significant post-propensity score matching. A non-linear relationship was identified, with an inflection point at HRR = 10.81 (P for non-linearity < 0.001), above which the protective effect strengthened with increasing HRR. Mediation analyses revealed diastolic blood pressure (15.9% mediation) and HbA1c (60.5% competitive mediation) as partial mediators of the HRR-DR association. HRR was also inversely associated with DR severity, particularly proliferative DR (vs. mild non-proliferative DR: OR = 0.67, P = 0.030; vs. severe non-proliferative DR: OR = 0.04, P = 0.002). Conclusions HRR is negatively correlated with DR onset and progression, highlighting its potential as a cost-effective biomarker for DR risk stratification.