Fat-free mass and glucose homeostasis: is greater fat-free mass an independent predictor of insulin resistance?

  • Ahmed Ghachem
  • Jean-Christophe Lagacé
  • Martin Brochu
  • Isabelle J. DionneEmail author
Original Article



A greater fat-free mass (FFM) is purported to be associated with protective effects on insulin resistance (IR). However, recent studies suggested negative associations between FFM and IR.


(1) To explore the direction of the association between FFM and IR in a large heterogeneous sample after controlling for confounding factors. (2) To determine cut off values of FFM associated with an increased risk of IR.


Outcome variables were measured in 7044 individuals (48.6% women, 20–79 years; NHANES, 1999–2006): body composition [fat mass (FM), FFM and appendicular FFM (aFFM); DXA], FFM index [FFMI: FFM/height (kg/m2)], appendicular FFMI [aFFM/height (kg/m2)] and insulin resistance (HOMA-IR). Multivariate regression analyses were performed to determine the independent predictors of HOMA-IR in younger (20–49 years) and older (50–79 years) men and women. ROC analyses were used to determine FFM cut-offs to identify a higher risk of insulin resistance (HOMA-IR > 75th percentile).


aFFMI was an independent predictor of IR in younger (men: β = 0.21; women: β = 0.31; all p ≤ 0.001) and older (men: β = 0.11; women: β = 0.37; all p ≤ 0.001) individuals. Thresholds for aFFMI at which the risk of IR was significantly increased were 8.96 and 8.39 kg/m2 in younger and older men, and 7.22 and 6.64 kg/m2 in younger and older women, respectively.


Independently of age, a greater aFFMI was an independent predictor of IR. These results suggest revisiting how we envision the link between FFM and IR and explore potential mechanisms.


Fat-free mass Fat-free mass thresholds Insulin resistance HOMA-IR 


Author Contributions

A.G and J-C.L, both contributed to the review of literature, database design, statistical analysis, interpretation of the data and drafting of the manuscript. M.B and I.D contributed to the drafting and revision of the manuscript. All of the authors approved the final manuscript prior to submission and they are guarantors of this work and take responsibility for the integrity of the data and the accuracy of the data analysis.

Compliance with ethical standards

Conflict of interest

All authors declare no conflict of interest.

Ethical approval

The protocol was approved by the National Center for Health Statistics.

Informed consent

All participants provided written and informed consent.


  1. 1.
    Cameron AJ, Shaw JE, Zimmet PZ (2004) The metabolic syndrome: prevalence in worldwide populations. Endocrinol Metab Clin N Am 33:351–375CrossRefGoogle Scholar
  2. 2.
    Balkau B et al (2003) The incidence and persistence of the NCEP (National Cholesterol Education Program) metabolic syndrome. The French D.E.S.I.R. study. Diabetes Metab 29:526–532CrossRefPubMedGoogle Scholar
  3. 3.
    Pararasa C, Bailey CJ, Griffiths HR (2015) Ageing, adipose tissue, fatty acids and inflammation. Biogerontology 16:235–248CrossRefPubMedGoogle Scholar
  4. 4.
    Lipscombe LL, Hux JE (2007) Trends in diabetes prevalence, incidence, and mortality in Ontario, Canada 1995–2005: a population-based study. Lancet 369:750–756CrossRefPubMedGoogle Scholar
  5. 5.
    Cleasby ME, Jamieson PM, Atherton PJ (2016) Insulin resistance and sarcopenia: mechanistic links between common co-morbidities. J Endocrinol 229:R67–R81CrossRefPubMedGoogle Scholar
  6. 6.
    Yang J (2014) Enhanced skeletal muscle for effective glucose homeostasis. Prog Mol Biol Transl Sci 121:133–163CrossRefPubMedGoogle Scholar
  7. 7.
    Miller WJ, Sherman WM, Ivy JL (1984) Effect of strength training on glucose tolerance and post-glucose insulin response. Med Sci Sports Exerc 16:539–543PubMedGoogle Scholar
  8. 8.
    Szczypaczewska M, Nazar K, Kaciuba-Uscilko H (1989) Glucose tolerance and insulin response to glucose load in body builders. Int J Sports Med 10:34–37CrossRefPubMedGoogle Scholar
  9. 9.
    Albright A et al (2000) American College of Sports Medicine position stand. Exercise and type 2 diabetes. Med Sci Sports Exerc 32:1345–1360CrossRefPubMedGoogle Scholar
  10. 10.
    Canadian Diabetes Association Clinical Practice Guidelines Expert (2013) Physical activity and diabetes. Can J Diabetes 37:S40–S44Google Scholar
  11. 11.
    Perreault K et al (2016) Association between fat free mass and glucose homeostasis: common knowledge revisited. Ageing Res Rev 28:46–61CrossRefPubMedGoogle Scholar
  12. 12.
    Aubertin-Leheudre M et al (2006) Effect of sarcopenia on cardiovascular disease risk factors in obese postmenopausal women. Obesity (Silver Spring) 14:2277–2283CrossRefGoogle Scholar
  13. 13.
    Goulet ED et al (2007) No difference in insulin sensitivity between healthy postmenopausal women with or without sarcopenia: a pilot study. Appl Physiol Nutr Metab 32:426–433CrossRefPubMedGoogle Scholar
  14. 14.
    Barsalani R, Brochu M, Dionne IJ (2013) Is there a skeletal muscle mass threshold associated with the deterioration of insulin sensitivity in sedentary lean to obese postmenopausal women? Diabetes Res Clin Pract 102:123–128CrossRefPubMedGoogle Scholar
  15. 15.
    Brochu M et al (2008) Contribution of the lean body mass to insulin resistance in postmenopausal women with visceral obesity: a Monet study. Obesity (Silver Spring) 16:1085–1093CrossRefGoogle Scholar
  16. 16.
    Lebon J et al (2012) Is a small muscle mass index really detrimental for insulin sensitivity in postmenopausal women of various body composition status? J Musculoskelet Neuronal Interact 12:116–126PubMedGoogle Scholar
  17. 17.
    Goulet ED et al (2009) Frailty in the elderly is associated with insulin resistance of glucose metabolism in the postabsorptive state only in the presence of increased abdominal fat. Exp Gerontol 44:740–744CrossRefPubMedGoogle Scholar
  18. 18.
    Glouzon BK et al (2015) Muscle mass and insulin sensitivity in postmenopausal women after 6-month exercise training. Climacteric 18:846–851CrossRefPubMedGoogle Scholar
  19. 19.
    Myette-Cote E et al (2015) Changes in glucose disposal after a caloric restriction-induced weight loss program in obese postmenopausal women: characteristics of positive and negative responders in a Montreal–Ottawa New Emerging Team study. Menopause 22:96–103CrossRefPubMedGoogle Scholar
  20. 20.
    Kuk JL et al (2008) Whole-body skeletal muscle mass is not related to glucose tolerance or insulin sensitivity in overweight and obese men and women. Appl Physiol Nutr Metab 33:769–774CrossRefPubMedGoogle Scholar
  21. 21.
    Curtin LR et al (2012) The National Health and Nutrition Examination Survey: sample design, 1999–2006. Vital Health Stat 2:1–39Google Scholar
  22. 22.
    Hoaglin DC, Iglewicz B (1987) Fine-tuning some resistant rules for outlier labeling. J Am Stat Assoc 82:1147–1149CrossRefGoogle Scholar
  23. 23.
    Hoaglin DC, Iglewicz B, Tukey JW (1986) Performance of some resistant rules for outlier labeling. J Am Stat Assoc 81:991–999CrossRefGoogle Scholar
  24. 24.
    Deschenes MR (2004) Effects of aging on muscle fibre type and size. Sports Med 34:809–824CrossRefPubMedGoogle Scholar
  25. 25.
    Karelis AD et al (2005) The metabolically healthy but obese individual presents a favorable inflammation profile. J Clin Endocrinol Metab 90:4145–4150CrossRefPubMedGoogle Scholar
  26. 26.
    Schutz Y, Kyle UU, Pichard C (2002) Fat-free mass index and fat mass index percentiles in Caucasians aged 18–98 y. Int J Obes Relat Metab Disord 26:953–960CrossRefPubMedGoogle Scholar
  27. 27.
    Kyle UG et al (2003) Body composition interpretation. Contributions of the fat-free mass index and the body fat mass index. Nutrition 19:597–604CrossRefPubMedGoogle Scholar
  28. 28.
    Kyle UG et al (2004) Aging, physical activity and height-normalized body composition parameters. Clin Nutr 23:79–88CrossRefPubMedGoogle Scholar
  29. 29.
    Brochu M et al (1999) Are aerobically fit older individuals more physically active in their free-living time? A doubly labeled water approach. J Clin Endocrinol Metab 84:3872–3876PubMedGoogle Scholar
  30. 30.
    Gallagher D et al (1997) Appendicular skeletal muscle mass: effects of age, gender, and ethnicity. J Appl Physiol (1985) 83:229–239CrossRefGoogle Scholar
  31. 31.
    Prevention Cf.D.C.a. and N.C.f.H. Statistic (2017) National Health and Nutrition Examination Survey (NHANES) Questionnaire (or examination protocol, or laboratory protocol) 2011–2012. Accessed 14 Dec 2017
  32. 32.
    Willi C et al (2007) Active smoking and the risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 298:2654–2664CrossRefPubMedGoogle Scholar
  33. 33.
    Carlsson S, Hammar N, Grill V (2005) Alcohol consumption and type 2 diabetes meta-analysis of epidemiological studies indicates a U-shaped relationship. Diabetologia 48:1051–1054CrossRefPubMedGoogle Scholar
  34. 34.
    Marin P et al (1994) Muscle fiber composition and capillary density in women and men with NIDDM. Diabetes Care 17:382–386CrossRefPubMedGoogle Scholar
  35. 35.
    Nyholm B et al (1997) Evidence of an increased number of type IIb muscle fibers in insulin-resistant first-degree relatives of patients with NIDDM. Diabetes 46:1822–1828CrossRefPubMedGoogle Scholar
  36. 36.
    Prior SJ et al (2009) Reduced skeletal muscle capillarization and glucose intolerance. Microcirculation 16:203–212CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Lillioja S et al (1987) Skeletal muscle capillary density and fiber type are possible determinants of in vivo insulin resistance in man. J Clin Investig 80:415–424CrossRefPubMedGoogle Scholar
  38. 38.
    Snijders T et al (2017) Muscle fiber capillarization as determining factor on indices of insulin sensitivity in humans. Physiol Rep 5:e13278CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Goodpaster BH et al (2000) Intramuscular lipid content is increased in obesity and decreased by weight loss. Metabolism 49:467–472CrossRefPubMedGoogle Scholar
  40. 40.
    Roden M (2004) How free fatty acids inhibit glucose utilization in human skeletal muscle. News Physiol Sci 19:92–96PubMedGoogle Scholar
  41. 41.
    Summers SA (2006) Ceramides in insulin resistance and lipotoxicity. Prog Lipid Res 45:42–72CrossRefPubMedGoogle Scholar
  42. 42.
    Addison O et al (2014) Intermuscular fat: a review of the consequences and causes. Int J Endocrinol 2014:309570CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Park SW et al (2009) Excessive loss of skeletal muscle mass in older adults with type 2 diabetes. Diabetes Care 32:1993–1997CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Lee CG et al (2011) Insulin sensitizers may attenuate lean mass loss in older men with diabetes. Diabetes Care 34:2381–2386CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Park SW et al (2007) Accelerated loss of skeletal muscle strength in older adults with type 2 diabetes: the health, aging, and body composition study. Diabetes Care 30:1507–1512CrossRefPubMedGoogle Scholar
  46. 46.
    Atlantis E et al (2009) Inverse associations between muscle mass, strength, and the metabolic syndrome. Metabolism 58:1013–1022CrossRefPubMedGoogle Scholar
  47. 47.
    Kalyani RR et al (2012) Glucose and insulin measurements from the oral glucose tolerance test and relationship to muscle mass. J Gerontol A Biol Sci Med Sci 67:74–81CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Faculty of Physical Activity SciencesUniversity of SherbrookeSherbrookeCanada
  2. 2.Research Centre on Aging, Social Services and Health CentreUniversity Institute of Geriatrics of SherbrookeSherbrookeCanada

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