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Do worse baseline risk factors explain the association of healthy obesity with increased mortality risk? Whitehall II Study

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posted on 08.07.2019, 14:42 by William Johnson, Joshua A. Bell, Ellie Robson, Tom Norris, Mika Kivimäki, Mark Hamer
Objective To describe 20-year risk factor trajectories according to initial weight/health status and investigate the extent to which baseline differences explain greater mortality among metabolically healthy obese (MHO) individuals than healthy non-obese individuals. Methods The sample comprised 6529 participants in the Whitehall II study who were measured serially between 1991–1994 and 2012–2013. Baseline weight (non-obese or obese; body mass index (BMI) ≥30 kg/m2) and health status (healthy or unhealthy; two or more of hypertension, low high-density lipoprotein cholesterol (HDL-C), high triglycerides, high glucose, and high homeostatic model assessment of insulin resistance (HOMA-IR)) were defined. The relationships of baseline weight/health status with 20-year trajectories summarizing ~25,000 observations of systolic and diastolic blood pressures, HDL-C, triglycerides, glucose, and HOMA-IR were investigated using multilevel models. Relationships of baseline weight/health status with all-cause mortality up until July 2015 were investigated using Cox proportional hazards regression. Results Trajectories tended to be consistently worse for the MHO group compared to the healthy non-obese group (e.g., glucose by 0.21 (95% CI 0.09, 0.33; p < 0.001) mmol/L at 20-years of follow-up). Consequently, the MHO group had a greater risk of mortality (hazard ratio 2.11 (1.24, 3.58; p = 0.006)) when the referent group comprised a random sample of healthy non-obese individuals. This estimate, however, attenuated (1.34 (0.85, 2.13; p = 0.209)) when the referent group was matched to the MHO group on baseline risk factors. Conclusions Worse baseline risk factors may explain any difference in mortality risk between obese and non-obese groups both labelled as healthy, further challenging the concept of MHO.

Funding

This work was supported by the UK Medical Research Council (WJ New Investigator Research Grant: MR/P023347/1). W.J. and M.H. acknowledge support from the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, which is a partnership between University Hospitals of Leicester NHS Trust, Loughborough University, and the University of Leicester. J.A.B. is supported by a Cancer Research UK programme grant (C18281/A19169). The UK Medical Research Council (MR/K013351/1; G0902037), British Heart Foundation (RG/13/2/30098, PG/11/63/29011), and the US National Institutes of Health (R01HL36310, R01AG013196) have supported collection of data in the Whitehall II Study. M.K. was additionally supported by NordForsk and a Helsinki Institute of Life Science fellowship.

History

Citation

International Journal of Obesity, 2018

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Health Sciences

Version

VoR (Version of Record)

Published in

International Journal of Obesity

Publisher

Springer Nature

issn

0307-0565

Acceptance date

25/07/2018

Copyright date

2018

Available date

08/07/2019

Publisher version

https://www.nature.com/articles/s41366-018-0192-0

Notes

We thank all participants in the Whitehall II Study, Whitehall II researchers, and support staff who make the study possible. Please refer to the Whitehall II data sharing policy at http://www.ucl.ac.uk/whitehallII/data-sharing. Whitehall II data are available to bona fide researchers for research purposes

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en

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