Total Bilirubin Predicts Severe Progression of Diabetic Retinopathy and the Possible Causal Mechanism

Early detection and treatment are key to delaying the progression of diabetic retinopathy (DR), avoiding loss of vision, and reducing the burden of advanced disease. Our study is aimed at determining if total bilirubin has a predictive value for DR progression and exploring the potential mechanism involved in this pathogenesis. A total of 540 patients with nonproliferative diabetic retinopathy (NPDR) were enrolled between July 2014 and September 2016 and assigned into a progression group (N = 67) or a stable group (N = 473) based on the occurrence of diabetic macular edema (DME), vitreous hemorrhage, retinal detachment, or other conditions that may cause severe loss of vision following a telephonic interview in August 2019. After further communication, 108 patients consented to an outpatient consultation between September and November 2019. Our findings suggest the following: (1) TBIL were significant independent predictors of DR progression (HR: 0.70, 95% CI: 0.54–0.89, p = 0.006). (2) Examination of outpatients indicated that compared to stable group patients, progression group patients had more components of urobilinogen and LPS but a lower concentration of TBIL. The relationship between bilirubin and severe DR was statistically significant after adjusting for sex, age, diabetes duration, type of diabetes, FPG, and HbA1c (OR: 0.70, 95% CI: 0.912–0.986, p = 0.016). The addition of serum LPS and/or urobilinogen attenuated this association. This study concludes that total bilirubin predicts an increased risk of severe DR progression. Decreasing bilirubin might be attributed to the increased levels of LPS and urobilinogen, which may indicate that the change of bilirubin levels is secondary to intestinal flora disorder and/or intestinal barrier destruction. Further prospective investigations are necessary to explore the causal associations for flora disorder, intestinal barrier destruction, and DR.