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Does inflammation mediate the association between obesity and hearing status in mid-childhood and mid-life?

Abstract

Background

Obesity is characterized by heightened inflammation, and both phenotypes are associated with hearing loss. We aimed to determine if inflammation mediates the associations between obesity and hearing ability in mid-childhood and mid-life.

Methods

Participants: 1165 11- to 12-year-old children and 1316 parents in the population-based cross-sectional Child Health CheckPoint within the Longitudinal Study of Australian Children. Adiposity measures: Body mass index (BMI) classified as normal, overweight and obesity; waist-to-height ratio (WHtR) classified as <0.5 and ≥0.5; fat mass index. Inflammatory biomarkers: Serum glycoprotein A (GlycA); high-sensitivity C-reactive protein (hsCRP). Audiometry: Composite high Fletcher Index (mean threshold of 1, 2, 4 kHz) in the better ear. Analysis: Causal mediation analysis decomposed a ‘total effect’ (obesity on hearing status) into ‘indirect’ effect via a mediator (eg GlycA, hsCRP) and ‘direct’ effect via other pathways, adjusting for age, sex and socioeconomic position.

Results

Compared to adults with BMI within the normal range, those with obesity had hearing thresholds 1.9 dB HL (95% CI 1.0–2.8) higher on the high Fletcher Index; 40% of the total effect was mediated via GlycA (indirect effect: 0.8 dB HL, 95% CI 0.1–1.4). Children with obesity had hearing thresholds 1.3 dB HL (95% CI 0.2–2.5) higher than those with normal BMI, of which 67% (indirect effect: 0.9 dB HL, 95% CI 0.4–1.4) was mediated via GlycA. Similar mediation effects were noted using other adiposity measures. Similar but less marked mediation effects were observed when hsCRP was used as the inflammatory biomarker (6–23% in adults and 23–33% in children).

Conclusions

Inflammation may play an important mediating role in the modest hearing reductions associated with obesity, particularly in children. These findings offer insights into possible mechanisms and early prevention strategies for hearing loss.

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Fig. 1: Causal mediation framework.
Fig. 2: Participants flowchart.
Fig. 3: Direct and indirect effects of obesity on hearing threshold through GlycA/hsCRP in children.
Fig. 4: Direct and indirect effects of obesity on hearing threshold through GlycA/hsCRP in adults.

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Acknowledgements

This article uses unit record data from Growing Up in Australia, the Longitudinal Study of Australian Children (LSAC). The study is conducted in partnership between the Department of Social Services, the Australian Institute of Family Studies, and the Australian Bureau of Statistics. The findings and views reported in this paper are solely those of the authors. MW and JW had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Research Electronic Data Capture (REDCap) tools were used in this study. More information about this software can be found at: www.project-redcap.org. We thank the LSAC and CheckPoint study participants, staff and students for their contributions.

Funding

This work was supported by the Australian National Health and Medical Research Council (NHMRC) Project Grants [1041352, 1109355]; The Royal Children’s Hospital Foundation [2014-241]; the Murdoch Children’s Research Institute; The University of Melbourne; the National Heart Foundation of Australia [100660]; Financial Markets Foundation for Children [2014-055, 2016-310]; and the Victorian Deaf Education Institute. Research at the Murdoch Children’s Research Institute is supported by the Victorian Government’s Operational Infrastructure Support Program. The funding bodies did not play any role in the study. JW and KL were supported by a Melbourne Children’s LifeCourse postdoctoral fellowship, funded by Royal Children’s Hospital Foundation grant [2018-984]. ML was supported by Melbourne Research Scholarship and the Murdoch Children’s Research Institute PhD Top Up Scholarship. The following authors were supported by the NHMRC: VS (Early Career Fellowship [1125687]), DB (Senior Research Fellowship [1064629]) and MW (Principal Research Fellowship [1160906]) in this work. VS was additionally supported by a Cottrell Research Fellowship from the Royal Australasian College of Physicians.

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MW conceived and led the CheckPoint study with the CheckPoint team, and was LSAC’s Health Design Leader. MW was the primary student supervisor, along with VS and RS, and oversaw all aspects of the study and the manuscript preparation. DB led the Metabolomics. JW performed data analysis and wrote the main paper. ML and AG advised on statistical issues and interpretation. MW, KL, RS and DB provided critical expert advice and critical review of this manuscript. All authors critically reviewed the manuscripts and had final approval of the submitted and published version of this paper.

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Correspondence to Melissa Wake.

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Wang, J., Liu, M., Sung, V. et al. Does inflammation mediate the association between obesity and hearing status in mid-childhood and mid-life?. Int J Obes 46, 1188–1195 (2022). https://doi.org/10.1038/s41366-022-01080-9

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