Mid-childhood fat mass and airflow limitation at 15 years: The mediating role of insulin resistance and C-reactive protein

Background: We previously reported an association of high fat mass levels from age 9 to 15 years with lower forced expiratory flow in 1 s (FEV₁ )/forced vital capacity (FVC) ratio (i.e., increased risk of airflow limitation) at 15 years. Here, we aimed to assess whether insulin resistance and C-reactive protein (CRP) at 15 years partially mediate this association.

Methods: We included 2263 children from the UK Avon Longitudinal Study of Parents and Children population-based cohort (ALSPAC). Four fat mass index (FMI) trajectories ("low," "medium-low," "medium-high," "high") from 9 to 15 years were previously identified using Group-Based Trajectory Modeling. Data on CRP, glucose, insulin, and post-bronchodilator FEV₁ /FVC were available at 15 years. We defined insulin resistance by the homeostasis model assessment-estimated insulin resistance index (HOMA-IR). We used adjusted linear regression models and a causal mediation analysis to assess the mediating role of HOMA-IR and CRP.

Results: Compared to children in the "low" FMI trajectory, children in the "medium-high" and "high" FMI trajectories had lower FEV₁ /FVC at 15 years. The percentage of the total effect explained by HOMA-IR was 19.8% [-114.1 to 170.0] and 20.4% [1.6 to 69.0] for the "medium-high" and "high" trajectories, respectively. In contrast, there was little evidence for a mediating role of CRP.

Conclusion: The association between mid-childhood fat mass and FEV₁ /FVC ratio at 15 years may be partially mediated by insulin resistance.