The U-Shaped Association between Bilirubin and Diabetic Retinopathy Risk: A Five-Year Cohort Based on 5323 Male Diabetic Patients

AIMS: This study aimed at assessing the impact of baseline bilirubin (TBiL) on the incidence of diabetic retinopathy (DR) based on a five-year cohort study which consisted of 5323 Chinese male diabetic patients. METHODS: A cohort study based on 5323 male diabetic patients was conducted in Beijing, from 2009 to 2013. Both baseline TBiL and follow-up changes were measured. Cox proportional risk model was used to calculate the hazard ratio (HR) of TBiL for DR risk. RESULTS: During the follow-up period, there were 269 new DR cases. The incidence of five-year follow-up was 5.1% (95% CI: 4.5%~5.6%). The TBiL level of those who had diabetic retinopathy was lower than that of those without (12.51+ 1.20 mol/L and 13.11+ 1.32 μmol/L, P = 0.033). And more interestingly, along with the quintiles of baseline TBiL, there showed a U-shaped curve with DR incidence. And the RRs were 0.928 (95% CI: 0.646–1.331), 0.544 (95% CI: 0.365–0.811), 0.913 (95% CI: 0.629–1.324), and 1.035 (95% CI: 0.725–1.479) for the second, third, fourth, and fifth quintiles of baseline TBiL levels, respectively, compared with the first quintile. For follow-up TBiL changes, after being adjusted for related covariables and baseline TBiL levels (as continuous variable) in the model, the RRs for DR were 1.411 (95% CI: 1.081–1.842) for those who had decreased TBiL level and 0.858 (95% CI: 0.770–0.947) for those who had increased TBiL level during follow-up. And this association was more prominent among those with lower baseline TBiL level. CONCLUSIONS: Serum TBiL had a U-shaped relationship with DR incidence, which was independent of control status of diabetes and other related covariates.