Epidemiology and Population Health

Levels and changes in body mass index decomposed into fat and fat-free mass index: relation to long-term all-cause mortality in the general population

Abstract

Background

In the general population, body mass index (BMI = weight (kg)/(height (m))2) shows a U-shaped relation to mortality, which is attributable to a combination of an inverse association with fat-free mass index (FFMI) and a direct association with fat mass index (FMI). However, preceding changes in body composition related to diseases, health behaviors, or social conditions that are also influencing later mortality may confound these associations.

Objective

To examine associations of FFMI and FMI, adjusted for preceding changes in FFMI and FMI over a 6 years period, with all-cause mortality in a healthy general population.

Methods

The study population was a random subset of adult Danes, participating in the Danish MONICA project; 989 men and 962 women, born 1922, 1932, 1942, and 1952, and examined in 1987–88 and 1993–94. They had no known major co-morbidities until start of follow-up in 1993–94, and were followed up for 18 years. Measures included height, weight, and bio-impedance, from which BMI, FFMI, and FMI were calculated, and information on educational level, smoking, alcohol drinking, leisure-time physical activity, which were obtained by questionnaires. We analyzed the relation between body composition and all-cause mortality by Cox proportional hazards model with splines, stratified by birth cohorts, and with adjustment for preceding changes in body composition and for the covariates including gender. We estimated hazard ratios (HR) with 95% confidence intervals (CI) relative to HR = 1.00 at the median values of BMI, FMI, and FFMI.

Results

During 18 years of follow-up, 286 men and 200 women died. BMI showed the well-known U-shaped association with mortality, and FMI was directly and FFMI inversely associated with mortality. Associations were not significantly modified by gender. Preceding changes in BMI, FMI, and FFMI were only weakly and not significantly associated with mortality. Associations for FMI and FFMI were monotonic, but curve-linear with a higher mortality above and below the respective median values of FMI and FFMI: at the 5th percentiles of FMI and FFMI, HRs were 0.80 (CI 0.57–1.13) and 2.01 (1.24–3.27), and at the 95th percentiles, HRs were 2.16 (1.38–3.38) and 0.81 (0.52–1.27), respectively.

Conclusions

In an apparently healthy general population, a large fat mass and a small fat-free mass are associated with greater risk of early mortality, also after adjusting for preceding changes in body composition, health behaviors, and educational level.

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Fig. 1: Flow-chart showing the formation of the study sample.
Fig. 2: Relationships of body composition and its preceding changes with mortality during 18 years of follow-up.

References

  1. 1.

    Bhaskaran K, Dos-Santos-Silva I, Leon DA, Douglas IJ, Smeeth L. Association of BMI with overall and cause-specific mortality: a population-based cohort study of 3·6 million adults in the UK. Lancet Diab Endocrinol. 2018;6:944–53.

    Article  Google Scholar 

  2. 2.

    Allison DB, Faith MS, Heo M, Kotler DP. Hypothesis concerning the U-shaped relation between body mass index and mortality. Am J Epidemiol. 1997;146:339–49.

    CAS  Article  Google Scholar 

  3. 3.

    Allison DB, Zhu SK, Plankey M, Faith MS, Heo M. Differential associations of body mass index and adiposity with all-cause mortality among men in the first and second National Health and Nutrition Examination Surveys (NHANES I and NHANES II) follow-up studies. Int J Obes Relat Metab Disord. 2002;26:410–6.

    CAS  Article  Google Scholar 

  4. 4.

    Zhu S, Heo M, Plankey M, Faith MS, Allison DB. Associations of body mass index and anthropometric indicators of fat mass and fat free mass with all-cause mortality among women in the first and second National Health and Nutrition Examination Surveys follow-up studies. Ann Epidemiol. 2003;13:286–93.

    Article  Google Scholar 

  5. 5.

    Heitmann BL, Erikson H, Ellsinger BM, Mikkelsen KL, Larsson B. Mortality associated with body fat, fat-free mass and body mass index among 60-year-old Swedish men-a 22-year follow-up. The study of men born in 1913. Int J Obes Relat Metab Disord. 2000;24:33–7.

    CAS  Article  Google Scholar 

  6. 6.

    Bigaard J, Frederiksen K, Tjønneland A, Thomsen BL, Overvad K, Heitmann BL, et al. Body fat and fat-free mass and all-cause mortality. Obes Res. 2004;12:1042–9.

    Article  Google Scholar 

  7. 7.

    Lee DH, Giovannucci EL. Body composition and mortality in the general population: a review of epidemiologic studies. Exp Biol Med. 2018;243:1275–85.

    CAS  Article  Google Scholar 

  8. 8.

    Carslake D, Davey Smith G, Gunnell D, Davies N, Nilsen TIL, Romundstad P. Confounding by ill health in the observed association between BMI and mortality: evidence from the HUNT Study using offspring BMI as an instrument. Int J Epidemiol. 2018;47:760–70.

    Article  Google Scholar 

  9. 9.

    De Stefani FDC, Pietraroia PS, Fernandes-Silva MM, Faria-Neto J, Baena CP. Observational evidence for unintentional weight loss in all-cause mortality and major cardiovascular events: a systematic review and meta-analysis. Sci Rep. 2018;8:15447.

    Article  Google Scholar 

  10. 10.

    Heitmann BL. Body fat in the adult Danish population aged 35-65 years: an epidemiological study. Int J Obes. 1991;15:535–45.

    CAS  PubMed  Google Scholar 

  11. 11.

    World Health Organization. The World Health Organization MONICA Project (monitoring trends and determinants in cardiovascular disease): a major international collaboration. WHO MONICA Project Principal Investigators. J Clin Epidemiol. 1988;41:105–14.

    Article  Google Scholar 

  12. 12.

    World Health Organization. Measuring obesity—classification and description of anthropometric data. Report on a WHO consultation of the epidemiology of obesity. Warsaw 21–23 October 1987. Nutrition Unit document, EUR/ICP/NUT 123. Copenhagen: WHO; 1989.

  13. 13.

    Heitmann BL. Prediction of body water and fat in adult Danes from measurement of electrical impedance. A validation study. Int J Obes. 1990;14:789–802.

    CAS  PubMed  Google Scholar 

  14. 14.

    Cox DR. Regression models and life-tables. J R Stat Soc (B). 1972;34:187–220.

    Google Scholar 

  15. 15.

    Korn EL, Graubard BI, Midthune. Time-to-event analysis of longitudinal follow-up of a survey: choise of the time-scale. Am J Epidemiol. 1997;145:72–80.

    CAS  Article  Google Scholar 

  16. 16.

    Therneau TM, Grambsch PM. Modeling survival data: extending the Cox model. New York: Springer; 2000.

    Google Scholar 

  17. 17.

    R Core Team. R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2018. https://www.R-project.org/.

  18. 18.

    Wood SN. Thin-plate regression splines. J Royal Stat Soc (B). 2003;65:95–114.

    Article  Google Scholar 

  19. 19.

    Wood SN, Pya N, Saefken B. Smoothing parameter and model selection for general smooth models (with discussion). J Am Stat Assoc. 2016;111:1548–75.

    CAS  Article  Google Scholar 

  20. 20.

    Lee DH, Keum N, Hu FB, Orav EJ, Rimm EB, Willett WC, et al. Predicted lean body mass, fat mass, and all cause and cause specific mortality in men: prospective US cohort study. BMJ. 2018;362:k2575.

    Article  Google Scholar 

  21. 21.

    Mulasi U, Kuchnia AJ, Cole AJ, Earthman CP. Bioimpedance at the bedside: current applications, limitations, and opportunities. Nutr Clin Pract. 2015;30:180–93.

    Article  Google Scholar 

  22. 22.

    Tournadre A, Vial G, Capel F, Soubrier M, Boirie Y. Sarcopenia. Joint Bone Spine. 2019;86:309–14.

    Article  Google Scholar 

  23. 23.

    Afzal S, Tybjærg-Hansen A, Jensen GB, Nordestgaard BG. Change in body mass index associated with lowest mortality in Denmark, 1976–2013. JAMA. 2016;315:1989–96.

    CAS  Article  Google Scholar 

  24. 24.

    St-Onge MP. Relationship between body composition changes and changes in physical function and metabolic risk factors in aging. Curr Opin Clin Nutr Metab Care. 2005;8:523–8.

    PubMed  Google Scholar 

  25. 25.

    Ma C, Avenell A, Bolland M, Hudson J, Stewart F, Robertson C, et al. Effects of weight loss interventions for adults who are obese on mortality, cardiovascular disease, and cancer: systematic review and meta-analysis. BMJ. 2017;359:j4849.

    Article  Google Scholar 

  26. 26.

    Berentzen T, Sørensen TI. Effects of intended weight loss on morbidity and mortality: possible explanations of controversial results. Nutr Rev. 2006;64:502–7.

    Article  Google Scholar 

  27. 27.

    Karahalios A, English DR, Simpson JA. Change in body size and mortality: a systematic review and meta-analysis. Int J Epidemiol. 2017;46:526–46.

    PubMed  Google Scholar 

  28. 28.

    Kim YH, Kim SM, Han KD, Son JW, Lee SS, Oh SW, et al. Taskforce Team of the obesity fact sheet of the Korean Society for the Study of Obesity. Change in weight and body mass index associated with all-cause mortality in Korea: a nationwide longitudinal study. J Clin Endocrinol Metab. 2017;102:4041–50.

    Article  Google Scholar 

  29. 29.

    Allison DB, Zannolli R, Faith MS, Heo M, Pietrobelli A, VanItallie TB, et al. Weight loss increases and fat loss decreases all-cause mortality rate: results from two independent cohort studies. Int J Obes Relat Metab Disord. 1999;23:603–11.

    CAS  Article  Google Scholar 

  30. 30.

    Graf CE, Herrmann FR, Spoerri A, Makhlouf AM, Sørensen TIA, Ho S, et al. Impact of body composition changes on risk of all-cause mortality in older adults. Clin Nutr. 2016;35:1499–505.

    Article  Google Scholar 

  31. 31.

    Østergaard JN, Grønbaek M, Schnohr P, Sørensen TI, Heitmann BL. Combined effects of weight loss and physical activity on all-cause mortality of overweight men and women. int J Obes. 2010;34:760–9.

    Article  Google Scholar 

  32. 32.

    Heitmann BL, Hills AP, Frederiksen P, Ward LC. Obesity, leanness, and mortality: effect modification by physical activity in men and women. Obesity. 2009;17:136–42.

    Article  Google Scholar 

  33. 33.

    Bigaard J, Frederiksen K, Tjønneland A, Thomsen BL, Overvad K, Heitmann BL, et al. Waist circumference and body composition in relation to all-cause mortality in middle-aged men and women. Int J Obes. 2005;29:778–84.

    CAS  Article  Google Scholar 

  34. 34.

    Kim YH, Kim SM, Han KD, Jung JH, Lee SS, Oh SW, et al. Waist circumference and all-cause mortality independent of body mass index in Korean population from the National Health Insurance Health Check-up 2009–2015. J Clin Med. 2019;8:1–10.

    Google Scholar 

Download references

Funding

The Parker Institute, Bispebjerg and Frederiksberg Hospital is supported by a core grant from the Oak Foundation (OCAY-13-309). The Novo Nordisk Foundation Center for Basic Metabolic is supported by The Novo Nordisk Foundation. Sources of funding had no role in the design, implementation, analysis, or interpretation of the data.

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Conceptualization: TIAS and BLH; study design: BLH; data collection: BLH; statistical analyses: PF; interpretation of results: TIAS, PF, and BLH; writing of first draft: TIAS; revision of the manuscript: TIAS, PF, and BLH; approval of the final version for submission: TIAS, PF, and BLH.

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Correspondence to Berit L. Heitmann.

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Sørensen, T.I.A., Frederiksen, P. & Heitmann, B.L. Levels and changes in body mass index decomposed into fat and fat-free mass index: relation to long-term all-cause mortality in the general population. Int J Obes (2020). https://doi.org/10.1038/s41366-020-0613-8

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