Gabriela P. Peralta, Raquel Granell, Annabelle Bédard, Anne‐Elie Carsin, Elaine Fuertes, Laura D. Howe, Sandra Márquez, Deborah L. Jarvis, Judith Garcia‐Aymerich, CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), Universität Zürich [Zürich] = University of Zurich (UZH), University of Bristol [Bristol], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hospital del Mar Medical Research Institute [Barcelona, Spain] (IMIM), Imperial College London, Wellcome Trust, WT, Medical Research Council, MRC: 076467/Z/05/Z, G0401540/73080, Generalitat de Catalunya, Ministerio de Ciencia e Innovación, MICINN, Horizon 2020: 633212, The present analyses are part of the Aging Lungs in European Cohorts (ALEC) Study ( www.alecstudy.org ), which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No. 633212. The content of this article reflects only the authors' views, and the European Commission is not liable for any use that may be made of the information contained therein. The UK Medical Research Council and Wellcome (Grant reference: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and Laura Howe and Raquel Granell will serve as guarantors for the contents of this paper. A comprehensive list of grant funding is available on the ALSPAC website ( http://www.bristol.ac.uk/alspac/external/documents/grant‐acknowledgements.pdf ). Specifically, grants from Wellcome Trust and MRC (076467/Z/05/Z and G0401540/73080) supported the collection of body composition and lung function data at 15 years. We acknowledge support from the Spanish Ministry of Science and Innovation through the 'Centro de Excelencia Severo Ochoa 2019–2023' Program (CEX2018‐000806‐S), and support from the Generalitat de Catalunya through the CERCA Program., European Project: 633212,H2020,H2020-PHC-2014-two-stage,ALEC(2015), HAL UVSQ, Équipe, and Aging Lungs in European Cohorts - ALEC - - H20202015-05-01 - 2019-04-30 - 633212 - VALID
Key MessageAlthough obesity measures have been consistently associated with a lower FEV1/FVC ratio in adolescents, no previous study has assessed the underlying mechanisms of this association This population-based study assessed whether insulin resistance and CRP levels at 15 years partially mediate the association between fat mass and FEV1/FVC using a causal mediation analysis approach. The findings suggest that insulin resistance at 15 years may mediate over 20% of this association, but no evidence of a mediating role of CRP was found. Further, longitudinal studies that evaluate other biomarkers of systemic inflammation and examine other potential mechanisms are needed to better understand the pathways linking obesity and respiratory health in adolescence. This is key for public health interventions and targeting clinical interventions.AbstractBackgroundWe 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.MethodsWe 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.ResultsCompared 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.ConclusionThe association between mid-childhood fat mass and FEV1/FVC ratio at 15 years may be partially mediated by insulin resistance.