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

Abstract

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

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

Methods: 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.

Results: 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).

Conclusion: 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.