Exploring the obesity paradox in chronic respiratory disease: the mediating effect of triglyceride-glucose index on mortality

Chronic respiratory diseases (CRD) are major contributors to mortality. The "obesity paradox" suggests that higher body mass index (BMI) may confer survival benefits in CRD patients. This study investigates the association between BMI and mortality risk in CRD patients, focusing on the mediating role of the triglyceride-glucose (TyG) index. A cross-sectional analysis of 7689 participants with CRD was conducted. Participants were categorized by BMI into <25.0, 25.0-29.9, 30.0-34.9, 35.0-39.9, and ≥40 kg/m². Outcomes included all-cause mortality, cardiovascular disease (CVD) mortality, and non-CVD mortality. Cox regression models assessed associations, and mediation analysis evaluated the role of the TyG index. Among 7689 CRD patients, higher BMI was associated with lower all-cause mortality (HR for BMI 25.0-29.9: 0.81, 95% CI 0.70-0.94; HR for BMI 30.0-34.9: 0.72, 95% CI 0.61-0.85; HR for BMI 35.0-39.9: 0.72, 95% CI 0.59-0.88; HR for BMI ≥ 40: 0.82, 95% CI 0.66-1.02) and non-CVD mortality (HR for BMI 25.0-29.9: 0.77, 95% CI 0.65-0.91; HR for BMI 30.0-34.9: 0.65, 95% CI 0.54-0.79; HR for BMI 35.0-39.9: 0.66, 95% CI 0.52-0.83; HR for BMI ≥ 40: 0.69, 95% CI 0.53-0.89), but not CVD mortality. The TyG index mediated a significant proportion of the association between BMI and mortality (mediation effects: -22.39 to -18.49%). Kaplan-Meier survival curves and restricted cubic spline regression further illustrated the significant associations between BMI and all-cause mortality and non-CVD mortality, while no significant association was observed for CVD mortality. Higher BMI is associated with lower mortality risk in CRD patients, particularly for non-CVD causes, mediated by the TyG index. This highlights the potential role of insulin resistance in the "obesity paradox" and suggests that metabolic health interventions may improve outcomes in CRD.