Total bilirubin modified the association between diabetes and stroke: a cross-sectional study from NHANES 2011-2016

Background Total bilirubin (TBIL) has antioxidant and anti-inflammatory properties. This study aimed to determine whether elevated TBIL could modify the association between diabetes and stroke. Method Data were obtained from the National Health and Nutrition Examination Survey 2011-2016. TBIL was stratified by median (10.3 mu mol/L). The association between diabetes and stroke was quantified using multivariable logistic regression models. The cut-off concentration for the presence of TBIL modification effects was identified by Johnson-Neyman analyses. Mediation analyses were performed to determine the influence of TBIL on mediating factors that mediate the relationship between diabetes and stroke. Results This cross-sectional study included 16 130 participants, with the mean age of 46.8 +/- 0.4 years and 48.5% of men. Diabetes was associated with the presence of stroke at TBIL <10.3 <mu>mol/L (OR=2.19, 95% CI 1.58 to 3.05) but not at TBIL >= 10.3 mu mol/L (OR=1.27, 95% CI 0.85 to 1.88) after adjustment for confounders. Above associations were significantly different between the two TBIL concentrations (P for interaction=0.03). Moreover, the modification effect of TBIL specifically occurred in men (P for interaction=0.02) rather than in women (P for interaction=0.08). The cut-off concentration for the presence of TBIL modification effects was 17.05 mu mol/L. Additionally, the TBIL of >= 10.3 mu mol/L inhibited mediating effects of hypersensitive C reactive protein (mediating effect=0.03, 95% CI -0.15 to 0.22, P=0.72) and systemic immune-inflammation index (mediating effect=0.01, 95% CI -0.01 to 0.04, P=0.29) as compared with the TBIL of <10.3 <mu>mol/L. Conclusions Elevated TBIL modified the association between diabetes and stroke through inhibiting mediating effects of inflammatory factors.