Abstract
Purpose
Evidence that metabolically healthy obesity (MHO) is a stable benign condition is unclear. The aim of this study was to estimate the transition of MHO subjects to unhealthy obesity (occurrence of cardio-metabolic events and/or risk factors) and its predictors.
Methods
We conducted an explorative follow-up study in a subset of MHO patients > 40 years without any cardio-metabolic risk factors and with normal LDL cholesterol (LDLc) levels, identified among 1530 obese patients. Due to the low sample size, a bootstrap approach was applied to identify the variables to be included in the final multivariate discrete-time logit model.
Results
The prevalence of MHO was 3.7%. During the follow-up (mean 6.1 years, SD 2.0), none of the MHO reported cardiovascular events, diabetes or prediabetes; 26 subjects developed risk factors (53% high LDLc and 50% hypertension). At the 6 and 12-year of follow-up, the cumulative incidence of transition to unhealthy obesity was 44% (95% CI 31–59%) and 62% (95% CI 45–79%), the incidence of high LDLc was 23% (95% CI 13–37%) and 40% (95% CI 25–59%) and that of hypertension was 20% (95% CI 11–33%) and 30% (95% CI 17–48%). LDLc and duration of follow-up were independent predictors of the transition from MHO to unhealthy obesity [OR 1.038 (1.005–1.072) and 1.360 (1.115–1.659)].
Conclusions
Results suggest that (a) MHO individuals do not move over time forward diabetes/prediabetes but develop risk factors, such as hypertension and higher LDL c that worsen the cardiovascular prognosis; (b) LDLc and the flow of time independently predict the transition to unhealthy status.
Level of evidence
Level III, cohort study.
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References
Jung CH, Lee WJ, Song KH (2017) Metabolically healthy obesity: a friend or foe? Korean J Intern Med 32:611–621. https://doi.org/10.3904/kjim.2016.259
Phillips CM (2017) Metabolically healthy obesity across the life course: epidemiology, determinants, and implications. Ann N Y Acad Sci 1391:85–100. https://doi.org/10.1111/nyas.13230
Bosello O, Donataccio MP, Cuzzolaro M (2016) Obesity or obesities? Controversies on the association between body mass index and premature mortality. Eat Weight Disord 21:165–174. https://doi.org/10.1007/s40519-016-0278-4
Rey-López JP, de Rezende LF, Pastor-Valero M, Tess BH (2014) The prevalence of metabolically healthy obesity: a systematic review and critical evaluation of the definitions used. Obes Rev 15:781–790. https://doi.org/10.1111/obr.12198
Lin H, Zhang L, Zheng R, Zheng Y (2017) The prevalence, metabolic risk and effects of lifestyle intervention for metabolically healthy obesity: a systematic review and meta-analysis: a PRISMA-compliant article. Medicine (Baltimore) 96:e8838. https://doi.org/10.1097/MD.0000000000008838
Bell JA, Hamer M, Sabia S, Singh-Manoux A, Batty GD, Kivimaki M (2015) The natural course of healthy obesity over 20 years. J Am Coll Cardiol 65:101–102. https://doi.org/10.1016/j.jacc.2014.09.077
Kim NH, Seo JA, Cho H, Seo JH, Yu JH, Yoo HJ et al (2016) Risk of the development of diabetes and cardiovascular disease in metabolically healthy obese people: the Korean genome and epidemiology study. Medicine (Baltimore) 95:e3384. https://doi.org/10.1097/MD.0000000000003384
Mongraw-Chaffin M, Foster MC, Anderson CAM, Burke GL, Haq N, Kalyani RR et al (2018) Metabolically healthy obesity, transition to metabolic syndrome, and cardiovascular risk. J Am Coll Cardiol 71:1857–1865. https://doi.org/10.1016/j.jacc.2018.02.055
Magkos F, Mohammed BS, Mittendorfer B (2008) Effect of obesity on the plasma lipoprotein subclass profile in normoglycemic and normolipidemic men and women. Int J Obes 32:1655–1664. https://doi.org/10.1038/ijo.2008.164
Pataky Z, Makoundou V, Nilsson P, Gabriel RS, Lalic K, Muscelli E et al (2011) Metabolic normality in overweight and obese subjects. Which parameters? Which risks? Int J Obes 35:1208–1215. https://doi.org/10.1038/ijo.2010.264
Appleton SL, Seaborn CJ, Visvanathan R, Hill CL, Gill TK, Taylor AW et al (2013) Diabetes and cardiovascular disease outcomes in the metabolically healthy obese phenotype: a cohort study. Diabetes Care 36:2388–2394. https://doi.org/10.2337/dc12-1971
Gilardini L, Redaelli G, Croci M, Conti A, Pasqualinotto L, Invitti C (2016) Effect of a modest weight loss in normalizing blood pressure in obese subjects on antihypertensive drugs. Obes Facts 9:251–258. https://doi.org/10.1159/000445504
Buyukkaya E, Karakas MF, Karakas E, Akçay AB, Tanboga IH, Kurt M et al (2014) Correlation of neutrophil to lymphocyte ratio with the presence and severity of metabolic syndrome. Clin Appl Thromb Hemost 20:159–163. https://doi.org/10.1177/1076029612459675
Maul A (1994) A discrete time logistic regression model for analyzing censored survival data. Environmetrics 5:145–157
Sauerbrei W, Schumacher M (1992) A bootstrap resampling procedure for model building: application to the Cox regression model. Stat Med 11:2093–2109
Goff DC, Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB, Gibbons R et al (2014) 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 63:2935–2959. https://doi.org/10.1016/j.jacc.2013.11.005
Soriguer F, Gutiérrez-Repiso C, Rubio-Martín E, García-Fuentes E, Almaraz MC, Colomo N et al (2013) Metabolically healthy but obese, a matter of time? Findings from the prospective Pizarra study. J Clin Endocrinol Metab 98:2318–2325. https://doi.org/10.1210/jc.2012-4253
Hwang YC, Hayashi T, Fujimoto WY, Kahn SE, Leonetti DL, McNeely MJ et al (2015) Visceral abdominal fat accumulation predicts the conversion of metabolically healthy obese subjects to an unhealthy phenotype. Int J Obes 39:1365–1370. https://doi.org/10.1038/ijo.2015.75
Lee SK, Kim SH, Cho GY, Baik I, Lim HE, Park CG et al (2013) Obesity phenotype and incident hypertension: a prospective community-based cohort study. J Hypertens 31:145–151. https://doi.org/10.1097/HJH.0b013e32835a3637
Borghi C, Urso R, Cicero AF (2017) Renin–angiotensin system at the crossroad of hypertension and hypercholesterolemia. Nutr Metab Cardiovasc Dis 27:115–120. https://doi.org/10.1016/j.numecd.2016.07.013
Pahlavani M, Kalupahana NS, Ramalingam L, Moustaid-Moussa N (2017) Regulation and functions of the renin-angiotensin system in white and brown adipose tissue. Compr Physiol 7:1137–1150. https://doi.org/10.1002/cphy.c160031
Dugail I, Le Lay S, Varret M, Le Liepvre X, Dagher G, Ferré P (2003) Review New insights into how adipocytes sense their triglyceride stores. Is cholesterol a signal? Horm Metab Res 35:204–210. https://doi.org/10.1055/s-2003-39475
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Gilardini, L., Zambon, A., Soranna, D. et al. Predictors of the transition from metabolically healthy obesity to unhealthy obesity. Eat Weight Disord 23, 739–744 (2018). https://doi.org/10.1007/s40519-018-0600-4
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DOI: https://doi.org/10.1007/s40519-018-0600-4