Indirect bilirubin is inversely associated with diabetic retinopathy risk and is a potential predictive biomarker

Diabetic retinopathy (DR) is a major cause of visual impairment and blindness. However, the current DR biomarkers are insufficient for accurately predicting its onset.

To identify a novel marker for predicting the risk of developing DR in patients with type 2 diabetes mellitus (T2DM).

We conducted a cross-sectional study involving 6993 hospitalized T2DM patients between 2013 and 2020. Patients were divided into two groups: The DR group and the non-DR group. Data were analyzed using univariate, correlation, multivariate, subgroup, and receiver operating characteristic curve analyses.

Total bilirubin, indirect bilirubin (IBIL), and direct bilirubin were negatively correlated with the risk of developing DR (P < 0.001). Moreover, these three factors were all positively correlated with clinical indicators related to DR, including the estimated glomerular filtration rate, the albumin/creatinine ratio, and the 1,25-dihydroxyvitamin D₃ level (P < 0.001). After adjusting for multiple variables, greater IBIL levels remained independently associated with a lower risk of developing DR (odds ratio = 0.500; 95% confidence interval: 0.363-0.686; P < 0.001). The optimal IBIL cutoff point for predicting the risk of DR in male patients with elevated diastolic blood pressure was 0.655 μmol/dL (area under the curve = 0.662).

These findings suggest that IBIL could be a valuable biomarker for predicting DR risk, offering a noninvasive, cost-effective, and readily available clinical tool for the early identification of high-risk patients. Future multicenter and longitudinal studies are warranted to validate these findings and further explore the biological mechanisms underlying the protective role of IBIL in DR.