Association between serum bilirubin and type 2 diabetes mellitus risk: Findings from a schizophrenia cohort

The relationship between serum bilirubin levels and type 2 diabetes mellitus (T2DM) in individuals with schizophrenia (SCZ) remains poorly understood. This study investigated associations between total, conjugated, and unconjugated bilirubin (TB, CB, and UCB) and T2DM risk, while exploring the potential role of inflammatory pathways.The study included 862 SCZ patients from Baiyun Jingkang Hospital, Guangzhou, the People's Republic of China. Cox proportional hazards model assessed baseline bilirubin and T2DM risk, while causal mediation analysis explored inflammatory markers. Latent class trajectory model and logistic regression model evaluated the association between multi-timepoint trajectories of bilirubin and T2DM prevalence.Over a median 3.19-year follow-up, 63 T2DM cases were diagnosed. Adjusted hazard ratios per 1 μmol/L increase were 0.88 (95 % CI: 0.82-0.95) for TB, 0.71 (0.57-0.89) for CB, and 0.86 (0.78-0.95) for UCB. Compared to the lowest tertile, the highest tertiles of TB, CB, and UCB were associated with 63 %, 74 %, and 63 % reduced T2DM risks, respectively. Lymphocyte count mediated TB (8.77 %), CB (11.68 %), and UCB (8.34 %); CRP mediated TB (3.33 %) and UCB (4.60 %) with T2DM. Persistently high TB and UCB levels were associated with lower T2DM prevalence (OR = 0.22 and 0.30, respectively).Elevated bilirubin levels are associated with reduced T2DM risk in SCZ patients, with lymphocyte count and CRP partially mediating the bilirubin-T2DM relationship. And persistently high levels of TB and UCB linked to a lower prevalence of T2DM. These findings suggest that moderately elevated serum bilirubin may reduce T2DM risk among SCZ patients.