Insulin resistance may be misdiagnosed by HOMA-IR in adults with greater fat-free mass: the ELSA-Brasil Study.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Additional Information
    • Source:
      Publisher: Springer Verlag Country of Publication: Germany NLM ID: 9200299 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-5233 (Electronic) Linking ISSN: 09405429 NLM ISO Abbreviation: Acta Diabetol Subsets: MEDLINE
    • Publication Information:
      Publication: Berlin : Springer Verlag
      Original Publication: Berlin : Springer International, c1991-
    • Subject Terms:
    • Abstract:
      Aims: Conflicting results have been reported on the association of fat-free mass (FFM) and insulin resistance (IR). This study sought to test the association of FFM and IR by indexing FFM to avoid collinearity with fat mass.
      Methods: This cross-sectional study comprised 11,284 volunteers, aged 38-79 years. Body composition was assessed by multi-frequency bioelectrical impedance. FFM indexed to body surface area (FFMbsa) was calculated. IR and impaired glucose tolerance (IGT) were estimated with homeostatic model assessment of insulin resistance index (HOMA-IR) and 2-h oral glucose tolerance test (2h-OGTT), respectively.
      Results: Percent body fat decreased from the 1st to the 5th quintile of FFMbsa in both women (Eta 2  = 0.166) and men (Eta 2  = 0.133). In women, fasting insulin (Eta 2  = 0.002), glucose (Eta 2  = 0.006), and HOMA-IR (Eta 2  = 0.007) increased slightly, but 2-h plasma glucose (2-h PG) was similar across the quintiles of FFMbsa. In men, fasting insulin and HOMA-IR were similar across the quintiles of FFMbsa, whereas fasting glucose increased slightly (Eta 2  = 0.002) and 2-h PG decreased (Eta 2  = 0.005) toward the highest quintile of FFMbsa. The higher the odds ratio for IR, the greater the FFMbsa in both sexes. Differently, FFMbsa did not affect the odds of IGT in women, while in men the odds ratio for IGT was lower in the 5th quintile compared with the 1st quintile of FFMbsa.
      Conclusions: Higher odds of IR associated with greater FFMbsa contrasted with lower odds of IGT associated with greater FFMbsa. IR may be misdiagnosed by HOMA-IR in adults with greater fat-free mass.
    • References:
      Ye J (2007) Role of insulin in the pathogenesis of free fatty acid-induced insulin resistance in skeletal muscle. Endocr Metab Immune Disord Drug Targets 7:65–74. (PMID: 10.2174/187153007780059423)
      Mlinar B, Marc J, Janez A, Pfeifer M (2007) Molecular mechanisms of insulin resistance and associated diseases. Clin Chim Acta 375:20–35. (PMID: 10.1016/j.cca.2006.07.005)
      Reaven GM (1988) Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37(12):1595–1607. (PMID: 10.2337/diab.37.12.1595)
      McLaughlin T, Abbasi F, Cheal K, Chu J, Lamendola C, Reaven G (2003) Use of metabolic markers to identify overweight individuals who are insulin resistant. Ann Intern Med 139:802–809. (PMID: 10.7326/0003-4819-139-10-200311180-00007)
      Reyes-Muñoz E, Ortega-González C, Martínez-Cruz N, Arce-Sánchez L, Estrada-Gutierrez G, Moran C et al (2016) Association of obesity and overweight with the prevalence of insulin resistance, pre-diabetes and clinical-biochemical characteristics among infertile Mexican women with polycystic ovary syndrome: a cross-sectional study. BMJ Open 6(7):e012107. (PMID: 10.1136/bmjopen-2016-012107)
      Risérus U, Arnlöv J, Berglund L (2007) Long-term predictors of insulin resistance: role of lifestyle and metabolic factors in middle-aged men. Diabetes Care 30(11):2928–2933. (PMID: 10.2337/dc07-0360)
      Yki-Jfirvinen H, Koivisto VA, Taskinen M-R, Nikkilfi EA (1984) Glucose tolerance, plasma lipoproteins, and tissue lipoprotein lipase activities in body builders. Eur J Appl Physiol 53:253–259. (PMID: 10.1007/BF00776599)
      Szczypaczewska M, Nazar K, Kaciuba-Uscilko H (1989) Glucose tolerance and insulin response to glucose load in body builders. Int J Sports Med 10(1):34–37. (PMID: 10.1055/s-2007-1024870)
      Castaneda C, Janssen I (2005) Ethnic comparisons of sarcopenia and obesity in diabetes. Ethn Dis 15:664–670. (PMID: 16259491)
      Srikanthan P, Karlamangla AS (2011) Relative muscle mass is inversely associated with insulin resistance and prediabetes. Findings from the third National Health and Nutrition Examination Survey. J Clin Endocrinol Metab 96(9):2898–2903. (PMID: 10.1210/jc.2011-0435)
      Weber DR, Leonard MB, Shults J, Zemel BS (2014) A comparison of fat and lean body mass index to BMI for the identification of metabolic syndrome in children and adolescents. J Clin Endocrinol Metab 99:3208–3216. (PMID: 10.1210/jc.2014-1684)
      Ghachem A, Lagacé JC, Brochu M, Dionne IJ (2019) Fat-free mass and glucose homeostasis: is greater fat-free mass an independent predictor of insulin resistance? Aging Clin Exp Res 31(4):447–454. (PMID: 10.1007/s40520-018-0993-y)
      Atlantis E, Martin SA, Haren MT, Taylor AW, Wittert GA (2009) Members of the Florey Adelaide Male Ageing Study. Inverse associations between muscle mass, strength, and the metabolic syndrome. Metabolism 58:1013–1022. (PMID: 10.1016/j.metabol.2009.02.027)
      Aubertin-Leheudre M, Lord C, Khalil A, Dionne IJ (2007) Effect of 6 months of exercise and isoflavone supplementation on clinical cardiovascular risk factors in obese postmenopausal women: a randomized, double-blind study. Menopause 14:624–629. (PMID: 10.1097/gme.0b013e31802e426b)
      Aquino EM, Barreto SM, Bensenor IM, Carvalho MS, Chor D, Duncan BB et al (2012) Brazilian Longitudinal Study of Adult Health (ELSA-Brasil): objectives and design. Am J Epidemiol 175(4):315–324. (PMID: 10.1093/aje/kwr294)
      Schmidt MI, Duncan BB, Mill JG, Lotufo PA, Chor D, Barreto SM, Aquino EM, Passos VM, Matos SM, Molina Mdel C, Carvalho MS, Bensenor IM (2015) Cohort Profile: Longitudinal Study of Adult Health (ELSA-Brasil). Int J Epidemiol 44(1):68–75. (PMID: 10.1093/ije/dyu027)
      Fedeli LG, Vidigal PG, Leite CM, Castilhos CD, Pimentel RA, Maniero VC et al (2013) Logistics of collection and transportation of biological samples and the organization of the central laboratory in the ELSA-Brasil. Rev Saude Publica 47(Suppl 2):63–71. (PMID: 10.1590/S0034-8910.2013047003807)
      Yarmolinsky J, Mueller NT, Duncan BB, Bisi Molina Mdel C, Goulart AC, Schmidt MI (2015) Coffee consumption, newly diagnosed diabetes, and other alterations in glucose homeostasis: a cross-sectional analysis of the longitudinal study of adult health (ELSA-Brasil). PLoS ONE 10(5):e0126469. (PMID: 10.1371/journal.pone.0126469)
      Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7):412–419. (PMID: 10.1007/BF00280883)
      Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (1997). Diabetes Care 20:1183–97.
      Perreault K, Lagacé J-C, Brochu M, Dionne IJ (2016) Association between fat free mass and glucose homeostasis: common knowledge revisited. Age Res Rev 28:46–61. (PMID: 10.1016/j.arr.2016.04.007)
      Deshmukh AS (2016) Insulin-stimulated glucose uptake in healthy and insulin-resistant skeletal muscle. Horm Mol Biol Clin Investig 26:13–24. (PMID: 26485752)
      Brochu M, Mathieu ME, Karelis AD, Doucet E, Lavoie ME, Garrel D, Rabasa-Lhoret R (2008) Contribution of the lean body mass to insulin resistance in postmenopausal women with visceral obesity: a Monet study. Obesity 16:1085–1093. (PMID: 10.1038/oby.2008.23)
      Lebon J, Aubertin-Leheudre M, Bobeuf F, Lord C, Labonte M, Dionne IJ (2012) Is a small muscle mass index really detrimental for insulin sensitivity in postmenopausal women of various body composition status? J Musculoskelet Neuronal Interact 12:116–126. (PMID: 22947543)
      Comerford KB, Almario RU, Kim K, Karakas SE (2012) Lean mass and insulin resistance in women with polycystic ovary syndrome. Metabolism 61:1256–1260. (PMID: 10.1016/j.metabol.2012.02.004)
      Tripathy D, Almgren P, Tuomi T, Groop L (2004) Contribution of insulin-stimulated glucose uptake and basal hepatic insulin sensitivity to surrogate measures of insulin sensitivity. Diab Care 27:2204–2210. (PMID: 10.2337/diacare.27.9.2204)
      Clark MG, Barrett EJ, Wallis MG, Vincent MA, Rattigan S (2002) The microvasculature in insulin resistance and type 2 diabetes. Semin Vasc Med 2(1):21–31. (PMID: 10.1055/s-2002-23506)
      Armstrong RB, Delp MD, Goljan EF, Laughlin MH (1987) Distribution of blood flow in muscles of miniature swine during exercise. J Appl Physiol 62(3):1285–1298. (PMID: 10.1152/jappl.1987.62.3.1285)
      Kahn BB, Rossetti L, Lodish HF, Charron MJ (1991) Decreased in vivo glucose uptake but normal expression of GLUT1 and GLUT4 in skeletal muscle of diabetic rats. J Clin Invest 87(6):2197–2206. (PMID: 10.1172/JCI115254)
      Tanner CJ, Barakat HA, Dohm GL, Pories WJ, MacDonald KG, Cunningham PR et al (2002) Muscle fiber type is associated with obesity and weight loss. Am J Physiol Endocrinol Metab 282:E1191–E1196. (PMID: 10.1152/ajpendo.00416.2001)
      Kamel Hosam K (2003) Sarcopenia and aging. Nutr Rev 61(51):157–167. (PMID: 10.1301/nr.2003.may.157-167)
      Storgaard H, Masbad S, Richter EA, Vaag AA (2007) Altered skeletal muscle fiber composition and size precede whole-body insulin resistance in young men with low birth weight. J Clin Endocrinol Metab 92(4):1530–1534. (PMID: 10.1210/jc.2006-2360)
      Alvim RO, Cheuhen MR, Machado SR, Sousa AG, Santos PC (2015) General aspects of muscle glucose uptake. An Acad Bras Cienc 87(1):351–368. (PMID: 10.1590/0001-3765201520140225)
      Lukaski HC, Bolonchuk WW, Hall CB, Siders WA (1986) Validation of tetrapolar bioelectrical impedance method to assess human body composition. J Appl Physiol 60(4):1327–1332. (PMID: 10.1152/jappl.1986.60.4.1327)
      Jensen B, Braun W, Geisler C, Both M, Klückmann K, Müller MJ, Bosy-Westphal A (2019) Limitations of fat-free mass for the assessment of muscle mass in obesity. Obes Facts 12:307–315. (PMID: 10.1159/000499607)
      Ritz P, Vol S, Berrut G, Tack I, Arnaud MJ, Tichet J (2008) Influence of gender and body composition on hydration and body water spaces. Clin Nutr 27(5):740–746. (PMID: 10.1016/j.clnu.2008.07.010)
    • Grant Information:
      01 06 0010.00 Ministério da Saúde; 01 06 0300.00 Ministério da Ciência, Tecnologia e Inovação
    • Contributed Indexing:
      Keywords: Fat-free mass; Glucose tolerance test; HOMA-IR; Insulin resistance
    • Accession Number:
      0 (Blood Glucose)
      0 (Insulin)
    • Publication Date:
      Date Created: 20200830 Date Completed: 20210305 Latest Revision: 20210305
    • Publication Date:
      20231215
    • Accession Number:
      10.1007/s00592-020-01594-6
    • Accession Number:
      32860145