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 µmol/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 µmol/L (OR=2.19, 95% CI 1.58 to 3.05) but not at TBIL ≥10.3 µmol/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 µmol/L. Additionally, the TBIL of ≥10.3 µmol/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 µmol/L.

Conclusions: Elevated TBIL modified the association between diabetes and stroke through inhibiting mediating effects of inflammatory factors.