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

Peralta, Gabriela P.; Granell, Raquel; Bédard, Annabelle, 1986-; Carsin, Anne-Elie; Fuertes, Elaine; Howe, Laura D.; Márquez, Sandra; Jarvis, Deborah; García Aymerich, Judith

doi:http://dx.doi.org/10.1111/pai.13894

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

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Peralta GP, Granell R, Bédard A, Carsin AE, Fuertes E, Howe LD, Márquez S, Jarvis DL, Garcia-Aymerich J. Mid-childhood fat mass and airflow limitation at 15 years: The mediating role of insulin resistance and C-reactive protein. Pediatr Allergy Immunol. 2022 Dec;33(12):e13894. DOI: 10.1111/pai.13894

Abstract

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.