Skip to main content
Top

08-14-2018 | Obesity | Article

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

Journal: International Journal of Obesity

Authors: William Johnson, Joshua A. Bell, Ellie Robson, Tom Norris, Mika Kivimäki, Mark Hamer

Publisher: Nature Publishing Group UK

Abstract

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.
Literature
1.
GBD 2015 Obesity Collaborators, Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, et al. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N Engl J Med. 2017;377:13–27.CrossRef
2.
Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: the Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016;37:2315–81.CrossRef
3.
Stefan N, Haring HU, Schulze MB Metabolically healthy obesity: the low-hanging fruit in obesity treatment? Lancet Diabetes Endocrinol. 2017. https://​doi.​org/​10.​1016/​S2213-8587(17)30292-9.
4.
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.CrossRef
5.
Bell JA, Hamer M, Batty GD, Singh-Manoux A, Sabia S, Kivimaki M. Incidence of metabolic risk factors among healthy obese adults: 20-year follow-up. J Am Coll Cardiol. 2015;66:871–3.CrossRef
6.
Bell JA, Hamer M, Sabia S, Singh-Manoux A, Batty GD, Kivimaki M. The natural course of healthy obesity over 20 years. J Am Coll Cardiol. 2015;65:101–2.CrossRef
7.
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.CrossRef
8.
den Engelsen C, Gorter KJ, Salome PL, Rutten GE. Development of metabolic syndrome components in adults with a healthy obese phenotype: a 3-year follow-up. Obesity. 2013;21:1025–30.CrossRef
9.
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.CrossRef
10.
Hamer M, Bell JA, Sabia S, Batty GD, Kivimaki M. Stability of metabolically healthy obesity over 8 years: the English Longitudinal Study of Ageing. Eur J Endocrinol. 2015;173:703–8.CrossRef
11.
Soriguer F, Gutierrez-Repiso C, Rubio-Martin E, Garcia-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.CrossRef
12.
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.CrossRef
13.
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.CrossRef
14.
Fan J, Song Y, Chen Y, Hui R, Zhang W. Combined effect of obesity and cardio-metabolic abnormality on the risk of cardiovascular disease: a meta-analysis of prospective cohort studies. Int J Cardiol. 2013;168:4761–8.CrossRef
15.
Gunter MJ, Xie X, Xue X, Kabat GC, Rohan TE, Wassertheil-Smoller S, et al. Breast cancer risk in metabolically healthy but overweight postmenopausal women. Cancer Res. 2015;75:270–4.CrossRef
16.
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.CrossRef
17.
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. 2017. https://​doi.​org/​10.​1093/​eurheartj/​ehx448.
18.
Murphy N, Cross AJ, Abubakar M, Jenab M, Aleksandrova K, Boutron-Ruault MC, et al. A nested case-control study of metabolically defined body size phenotypes and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). PLoS Med. 2016;13:e1001988CrossRef
19.
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;36:2294–300.CrossRef
20.
Sung KC, Ryu S, Cheong ES, Kim BS, Kim BJ, Kim YB, et al. All-cause and cardiovascular mortality among Koreans: effects of obesity and metabolic health. Am J Prev Med. 2015;49:62–71.CrossRef
21.
Marmot MG, Smith GD, Stansfeld S, Patel C, North F, Head J, et al. Health inequalities among British civil servants: the Whitehall II study. Lancet. 1991;337:1387–93.CrossRef
22.
Bouillon K, Singh-Manoux A, Jokela M, Shipley MJ, Batty GD, Brunner EJ, et al. Decline in low-density lipoprotein cholesterol concentration: lipid-lowering drugs, diet, or physical activity? Evidence from the Whitehall II study. Heart. 2011;97:923–30.CrossRef
23.
Goldberg DP The Detection of Psychiatric Illness by Questionnaire. London: Oxford University Press; 1972.
24.
Stringhini S, Sabia S, Shipley M, Brunner E, Nabi H, Kivimaki M, et al. Association of socioeconomic position with health behaviors and mortality. JAMA. 2010;303:1159–66.CrossRef
25.
Wildman RP, Muntner P, Reynolds K, McGinn AP, Rajpathak S, Wylie-Rosett J, et al. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999-2004). Arch Intern Med. 2008;168:1617–24.CrossRef
26.
Johnson W. Analytical strategies in human growth research. Am J Hum Biol. 2015;27:69–83.CrossRef
27.
Johnson W, Balakrishna N, Griffiths PL. Modeling physical growth using mixed effects models. Am J Phys Anthropol. 2013;150:58–67.CrossRef
28.
Leckie G, Charlton C. runmlwin: a program to run the MLwiN multilevel software from within Stata. J Stat Softw. 2012;52:1–40.CrossRef
29.
Bell JA, Kivimaki M, Hamer M. Metabolically healthy obesity and risk of incident type 2 diabetes: a meta-analysis of prospective cohort studies. Obes Rev. 2014;15:504–15.CrossRef
30.
Eckel N, Meidtner K, Kalle-Uhlmann T, Stefan N, Schulze MB. Metabolically healthy obesity and cardiovascular events: a systematic review and meta-analysis. Eur J Prev Cardiol. 2016;23:956–66.CrossRef
31.
Jokela M, Hamer M, Singh-Manoux A, Batty GD, Kivimaki M. Association of metabolically healthy obesity with depressive symptoms: pooled analysis of eight studies. Mol Psychiatry. 2014;19:910–4.CrossRef
32.
Kramer CK, Zinman B, Retnakaran R. Are metabolically healthy overweight and obesity benign conditions?: a systematic review and meta-analysis. Ann Intern Med. 2013;159:758–69.CrossRef
33.
Lotta LA, Abbasi A, Sharp SJ, Sahlqvist AS, Waterworth D, Brosnan JM, et al. Definitions of metabolic health and risk of future type 2 diabetes in BMI categories: a systematic review and network meta-analysis. Diabetes Care. 2015;38:2177–87.CrossRef
34.
Zhang J, Jiang H, Chen J. Combined effect of body mass index and metabolic status on the risk of prevalent and incident chronic kidney disease: a systematic review and meta-analysis. Oncotarget. 2017;8:35619–29.PubMed
35.
Gavrilova O, Marcus-Samuels B, Graham D, Kim JK, Shulman GI, Castle AL, et al. Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice. J Clin Invest. 2000;105:271–8.CrossRef
36.
Medina-Gomez G, Gray SL, Yetukuri L, Shimomura K, Virtue S, Campbell M, et al. PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. PLoS Genet. 2007;3:e64CrossRef
37.
Primeau V, Coderre L, Karelis AD, Brochu M, Lavoie ME, Messier V, et al. Characterizing the profile of obese patients who are metabolically healthy. Int J Obes. 2011;35:971–81.CrossRef
38.
Kilpelainen TO, Zillikens MC, Stancakova A, Finucane FM, Ried JS, Langenberg C, et al. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Nat Genet. 2011;43:753–60.CrossRef
39.
Batty GD, Shipley M, Tabak A, Singh-Manoux A, Brunner E, Britton A, et al. Generalizability of occupational cohort study findings. Epidemiology. 2014;25:932–3.CrossRef
40.
Kennedy AB, Lavie CJ, Blair SN. Fitness or fatness: which is more important? JAMA. 2018;319:231–2.CrossRef

Be confident that your patient care is up to date

Medicine Matters is being incorporated into Springer Medicine, our new medical education platform. 

Alongside the news coverage and expert commentary you have come to expect from Medicine Matters diabetes, Springer Medicine's complimentary membership also provides access to articles from renowned journals and a broad range of Continuing Medical Education programs. Create your free account »