Abstract
Background
Metabolically healthy obesity is not always a benign condition. It is associated with an increased incidence of cardiovascular disease and all-cause mortality. We investigated the prognostic significance of metabolically healthy obesity by comparing clinical profile-matched metabolically healthy obesity and non-obesity groups.
Methods
We analyzed a health insurance dataset with annual health checkup data from Japan. The analyzed data included 168,699 individuals aged <65 years. Obesity was defined as ≥25 kg/m2 body mass index. Metabolically healthy was defined as ≤1 metabolic risk factor (high blood pressure, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol, or high hemoglobin A1c). Incidence rates of stroke, myocardial infarction, and all-cause mortality identified from the insurance data were compared between metabolically healthy obesity and non-obesity groups (n = 8644 each) using a log-rank test.
Results
The stroke (obesity: 9.2 per 10,000 person-years; non-obesity: 10.5; log-rank test p = 0.595), myocardial infarction (obesity: 3.7; non-obesity: 3.1; p = 0.613), and all-cause mortality (obesity: 26.6; non-obesity: 23.2; p = 0.304) incidence rates did not differ significantly between the metabolically healthy obesity and non-obesity groups, even when the abdominal obesity was considered in the analysis. The lack of association was also observed in the comparison between the metabolically unhealthy obesity and non-obesity groups (n = 10,965 each). The population with metabolically healthy obesity reported negligibly worse metabolic profiles than the population with non-obesity at the 5.6-year follow-up.
Conclusion
Obesity, when accompanied by a healthy metabolic profile, did not increase the risk of cardiovascular outcomes and all-cause mortality.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Data availability
The datasets generated during and/or analyzed during the current study are not publicly available due ethical reason but are available from the corresponding author on reasonable request.
References
Johnson W, Bell JA, Robson E, Norris T, Kivimäki M, Hamer M. Do worse baseline risk factors explain the association of healthy obesity with increased mortality risk? Whitehall II Study. Int J Obes. 2019;43:1578–89. https://doi.org/10.1038/s41366-018-0192-0.
Bobbioni-Harsch E, Pataky Z, Makoundou V, Laville M, Disse E, Anderwald C, et al. From metabolic normality to cardiometabolic risk factors in subjects with obesity. Obesity. 2012;20:2063–9. https://doi.org/10.1038/oby.2012.69.
Appleton SL, Seaborn CJ, Visvanathan R, Hill CL, Gill TK, Taylor AW, et al. Diabetes and cardiovascular disease outcomes in the metabolically healthy obese phenotype: a cohort study. Diabetes Care. 2013;36:2388–94. https://doi.org/10.2337/dc12-1971.
Soriguer F, Gutiérrez-Repiso C, Rubio-Martín E, García-Fuentes E, Almaraz MC, Colomo N, et al. Metabolically healthy but obese, a matter of time? Findings from the prospective Pizarra study. J Clin Endocrinol Metab. 2013;98:2318–25. https://doi.org/10.1210/jc.2012-4253.
Aung K, Lorenzo C, Hinojosa MA, Haffner SM. Risk of developing diabetes and cardiovascular disease in metabolically unhealthy normal-weight and metabolically healthy obese individuals. J Clin Endocrinol Metab. 2014;99:462–8. https://doi.org/10.1210/jc.2013-2832.
Hinnouho GM, Czernichow S, Dugravot A, Nabi H, Brunner EJ, Kivimaki M, et al. Metabolically healthy obesity and the risk of cardiovascular disease and type 2 diabetes: the Whitehall II cohort study. Eur Heart J. 2015;36:551–9. https://doi.org/10.1093/eurheartj/ehu123.
Guo F, Garvey WT. Cardiometabolic disease risk in metabolically healthy and unhealthy obesity: stability of metabolic health status in adults. Obesity. 2016;24:516–25. https://doi.org/10.1002/oby.21344.
Caleyachetty R, Thomas GN, Toulis KA, Mohammed N, Gokhale KM, Balachandran K, et al. Metabolically healthy obese and incident cardiovascular disease events among 3.5 million men and women. J Am Coll Cardiol. 2017;70:1429–37. https://doi.org/10.1016/j.jacc.2017.07.763.
Lassale C, Tzoulaki I, Moons KGM, Sweeting M, Boer J, Johnson L, et al. Separate and combined associations of obesity and metabolic health with coronary heart disease: a pan-European case-cohort analysis. Eur Heart J. 2018;39:397–406. https://doi.org/10.1093/eurheartj/ehx448.
Commodore-Mensah Y, Lazo M, Tang O, Echouffo-Tcheugui JB, Ndumele CE, Nambi V, et al. High burden of subclinical and cardiovascular disease risk in adults with metabolically healthy obesity: the Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care. 2021;44:1657–63. https://doi.org/10.2337/dc20-2227.
Zhou Z, Macpherson J, Gray SR, Gill JMR, Welsh P, Celis-Morales C, et al. Are people with metabolically healthy obesity really healthy? A prospective cohort study of 381,363 UK Biobank participants. Diabetologia. 2021;64:1963–72. https://doi.org/10.1007/s00125-021-05484-6.
Hinnouho GM, Czernichow S, Dugravot A, Batty GD, Kivimaki M, Singh-Manoux A. Metabolically healthy obesity and risk of mortality: does the definition of metabolic health matter? Diabetes Care. 2013;36:2294–1300. https://doi.org/10.2337/dc12-1654.
Hamer M, Stamatakis E. Metabolically healthy obesity and risk of all-cause and cardiovascular disease mortality. J Clin Endocrinol Metab. 2012;97:2482–848. https://doi.org/10.1210/jc.2011-3475.
Itoh H, Kaneko H, Kiriyama H, Kamon T, Fujiu K, Morita K, et al. Metabolically healthy obesity and the risk of cardiovascular disease in the general population—analysis of a nationwide epidemiological database. Circ J. 2021;85:914–20. https://doi.org/10.1253/circj.CJ-20-1040.
Wu X, Zhao Y, Zhou Q, Han M, Qie R, Qin P, et al. All-cause mortality risk with different metabolic abdominal obesity phenotypes: the Rural Chinese Cohort Study. Br J Nutr. 2023;130:1637–44. https://doi.org/10.1017/S0007114523000673.
Wei Y, Wang R, Wang J, Han X, Wang F, Zhang Z, et al. Transitions in metabolic health status and obesity over time and risk of diabetes: the Dongfeng-Tongji cohort study. J Clin Endocrinol Metab. 2023;108:2024–32. https://doi.org/10.1210/clinem/dgad047.
Gao M, Lv J, Yu C, Guo Y, Bian Z, Yang R, et al. Metabolically healthy obesity, transition to unhealthy metabolic status, and vascular disease in Chinese adults: a cohort study. PLoS Med. 2020;17:e1003351. https://doi.org/10.1371/journal.pmed.1003351.
Smith GI, Mittendorfer B, Klein S. Metabolically healthy obesity: facts and fantasies. J Clin Invest. 2019;129:3978–89. https://doi.org/10.1172/JCI129186.
Nakatani E, Tabara Y, Sato Y, Tsuchiya A, Miyachi Y. Data resource profile of Shizuoka Kokuho Database (SKDB) using integrated health- and care-insurance claims and health checkups: the Shizuoka study. J Epidemiol. 2022;32:391–400. https://doi.org/10.2188/jea.JE20200480.
Tabara Y, Nakatani E, Miyachi Y. Body mass index, functional disability and all-cause mortality in 330 000 older adults: the Shizuoka study. Geriatr Gerontol Int. 2021;21:1040–6. https://doi.org/10.1111/ggi.14286.
Teramoto T, Sasaki J, Ueshima H, Egusa G, Kinoshita M, Shimamoto K, et al. Metabolic syndrome. J Atheroscler Thromb. 2008;15:1–5. https://doi.org/10.5551/jat.e580.
Park J, Kwon S, Choi EK, Choi YJ, Lee E, Choe W, et al. Validation of diagnostic codes of major clinical outcomes in a National Health Insurance database. Int J Arrhythm. 2019;20:5. https://doi.org/10.1186/s42444-019-0005-0.
Hayashida K, Murakami G, Matsuda S, Fushimi K. History and profile of Diagnosis Procedure Combination (DPC): development of a real data collection system for acute inpatient care in Japan. J Epidemiol. 2021;31:1–11. https://doi.org/10.2188/jea.JE20200288.
Zhang Z, Kim HJ, Lonjon G, Zhu Y, written on behalf of AME Big-Data Clinical Trial Collaborative Group. Balance diagnostics after propensity score matching. Ann Transl Med. 2019;7:16 https://doi.org/10.21037/atm.2018.12.10.
Cho YK, Kang YM, Yoo JH, Lee J, Park JY, Lee WJ, et al. Implications of the dynamic nature of metabolic health status and obesity on risk of incident cardiovascular events and mortality: a nationwide population-based cohort study. Metabolism. 2019;97:50–6. https://doi.org/10.1016/j.metabol.2019.05.002.
Lee HJ, Choi EK, Lee SH, Kim YJ, Han KD, Oh S. Risk of ischemic stroke in metabolically healthy obesity: a nationwide population-based study. PLoS ONE. 2018;13:e0195210. https://doi.org/10.1371/journal.pone.0195210.
Czernichow S, Kengne AP, Stamatakis E, Hamer M, Batty GD. Body mass index, waist circumference and waist-hip ratio: which is the better discriminator of cardiovascular disease mortality risk?: evidence from an individual-participant meta-analysis of 82 864 participants from nine cohort studies. Obes Rev. 2011;12:680–7. https://doi.org/10.1111/j.1467-789X.2011.00879.x.
NCD Risk Factor Collaboration (NCD-RisC). A century of trends in adult human height. Elife. 2016;5:e13410. https://doi.org/10.7554/eLife.13410.
Acknowledgements
We thank the Shizuoka Prefectural Government, 35 city and town offices in the Shizuoka Prefecture, and the Shizuoka Federation of National Health Insurance Organizations for their help in constructing the SKDB dataset. We also thank Crimson Interactive Pvt. Ltd. for their assistance in editing the English of this manuscript.
Funding
This study was supported by a public health research grant from Shizuoka Prefecture.
Author information
Authors and Affiliations
Contributions
YT was responsible for study designing, data analysis, and preparing manuscript, AA and AO contributed to revising the manuscript, YS contributed to preparing the dataset and revising the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Ethical approval
The study was conducted in accordance with the Declaration of Helsinki, and the study protocol was approved by the ethics committee of Shizuoka Graduate University of Public Health (SGUPH_2021_001). Approval was obtained from the review board of each municipality to use the health insurance data in a medical study. All personal information was anonymized by the Shizuoka Federation of National Health Insurance Organizations before releasing the dataset. Information about this study is available on the websites of the Shizuoka Prefectural Government Office and the Shizuoka Graduate University of Public Health to ensure that study participants are able to opt out of inclusion in the dataset as an alternative to obtaining written informed consent from the study participants.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Tabara, Y., Shoji-Asahina, A., Ogawa, A. et al. Metabolically healthy obesity and risks of cardiovascular disease and all-cause mortality, a matched cohort study: the Shizuoka study. Int J Obes (2024). https://doi.org/10.1038/s41366-024-01541-3
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41366-024-01541-3