title: Insulin Resistance Negatively Influences the Muscle-Dependent IGF-1-Bone Mass Relationship in Premenarcheal Girls.
abstract: BACKGROUND
  IGF-1 promotes bone growth directly and indirectly through its effects on skeletal muscle. Insulin and IGF-1 share a common cellular signaling process; thus, insulin resistance may influence the IGF-1-muscle-bone relationship.
  
  
  OBJECTIVE
  We sought to determine the effect of insulin resistance on the muscle-dependent relationship between IGF-1 and bone mass in premenarcheal girls.
  
  
  METHODS
  This was a cross-sectional study conducted at a university research center involving 147 girls ages 9 to 11 years.
  
  
  METHODS
  Glucose, insulin, and IGF-1 were measured from fasting blood samples. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from glucose and insulin. Fat-free soft tissue (FFST) mass and bone mineral content (BMC) were measured by dual-energy x-ray absorptiometry. Our primary outcome was BMC/height.
  
  
  RESULTS
  In our path model, IGF-1 predicted FFST mass (b = 0.018; P = .001), which in turn predicted BMC/height (b = 0.960; P < .001). IGF-1 predicted BMC/height (b = 0.001; P = .002), but not after accounting for the mediator of this relationship, FFST mass. The HOMA-IR by IGF-1 interaction negatively predicted FFST mass (b = -0.044; P = .034). HOMA-IR had a significant and negative effect on the muscle-dependent relationship between IGF-1 and BMC/height (b = -0.151; P = .047).
  
  
  CONCLUSIONS
  Lean body mass is an important intermediary factor in the IGF-1-bone relationship. For this reason, bone development may be compromised indirectly via suboptimal IGF-1-dependent muscle development in insulin-resistant children.
authors.affiliation: Department of Foods and Nutrition (J.M.K., E.M.L., R.D.L.), College of Family and Consumer Sciences, University of Georgia, Athens, Georgia 30602; Department of Pediatrics (N.K.P.), Georgia Prevention Institute, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912; Department of Kinesiology, College of Education (N.T.J.), and Department of Health and Human Development, College of Family and Consumer Sciences (O.A.), University of Georgia, Athens, Georgia 30602; and Department of Neuroscience and Regenerative Medicine (C.I.), and Department of Cellular Biology and Anatomy (M.H.), Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912.
authors.forename: J M
authors.initials: JM
authors.lastname: Kindler
authors.affiliation: Department of Foods and Nutrition (J.M.K., E.M.L., R.D.L.), College of Family and Consumer Sciences, University of Georgia, Athens, Georgia 30602; Department of Pediatrics (N.K.P.), Georgia Prevention Institute, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912; Department of Kinesiology, College of Education (N.T.J.), and Department of Health and Human Development, College of Family and Consumer Sciences (O.A.), University of Georgia, Athens, Georgia 30602; and Department of Neuroscience and Regenerative Medicine (C.I.), and Department of Cellular Biology and Anatomy (M.H.), Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912.
authors.forename: N K
authors.initials: NK
authors.lastname: Pollock
authors.affiliation: Department of Foods and Nutrition (J.M.K., E.M.L., R.D.L.), College of Family and Consumer Sciences, University of Georgia, Athens, Georgia 30602; Department of Pediatrics (N.K.P.), Georgia Prevention Institute, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912; Department of Kinesiology, College of Education (N.T.J.), and Department of Health and Human Development, College of Family and Consumer Sciences (O.A.), University of Georgia, Athens, Georgia 30602; and Department of Neuroscience and Regenerative Medicine (C.I.), and Department of Cellular Biology and Anatomy (M.H.), Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912.
authors.forename: E M
authors.initials: EM
authors.lastname: Laing
authors.affiliation: Department of Foods and Nutrition (J.M.K., E.M.L., R.D.L.), College of Family and Consumer Sciences, University of Georgia, Athens, Georgia 30602; Department of Pediatrics (N.K.P.), Georgia Prevention Institute, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912; Department of Kinesiology, College of Education (N.T.J.), and Department of Health and Human Development, College of Family and Consumer Sciences (O.A.), University of Georgia, Athens, Georgia 30602; and Department of Neuroscience and Regenerative Medicine (C.I.), and Department of Cellular Biology and Anatomy (M.H.), Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912.
authors.forename: N T
authors.initials: NT
authors.lastname: Jenkins
authors.affiliation: Department of Foods and Nutrition (J.M.K., E.M.L., R.D.L.), College of Family and Consumer Sciences, University of Georgia, Athens, Georgia 30602; Department of Pediatrics (N.K.P.), Georgia Prevention Institute, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912; Department of Kinesiology, College of Education (N.T.J.), and Department of Health and Human Development, College of Family and Consumer Sciences (O.A.), University of Georgia, Athens, Georgia 30602; and Department of Neuroscience and Regenerative Medicine (C.I.), and Department of Cellular Biology and Anatomy (M.H.), Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912.
authors.forename: A
authors.initials: A
authors.lastname: Oshri
authors.affiliation: Department of Foods and Nutrition (J.M.K., E.M.L., R.D.L.), College of Family and Consumer Sciences, University of Georgia, Athens, Georgia 30602; Department of Pediatrics (N.K.P.), Georgia Prevention Institute, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912; Department of Kinesiology, College of Education (N.T.J.), and Department of Health and Human Development, College of Family and Consumer Sciences (O.A.), University of Georgia, Athens, Georgia 30602; and Department of Neuroscience and Regenerative Medicine (C.I.), and Department of Cellular Biology and Anatomy (M.H.), Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912.
authors.forename: C
authors.initials: C
authors.lastname: Isales
authors.affiliation: Department of Foods and Nutrition (J.M.K., E.M.L., R.D.L.), College of Family and Consumer Sciences, University of Georgia, Athens, Georgia 30602; Department of Pediatrics (N.K.P.), Georgia Prevention Institute, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912; Department of Kinesiology, College of Education (N.T.J.), and Department of Health and Human Development, College of Family and Consumer Sciences (O.A.), University of Georgia, Athens, Georgia 30602; and Department of Neuroscience and Regenerative Medicine (C.I.), and Department of Cellular Biology and Anatomy (M.H.), Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912.
authors.forename: M
authors.initials: M
authors.lastname: Hamrick
authors.affiliation: Department of Foods and Nutrition (J.M.K., E.M.L., R.D.L.), College of Family and Consumer Sciences, University of Georgia, Athens, Georgia 30602; Department of Pediatrics (N.K.P.), Georgia Prevention Institute, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912; Department of Kinesiology, College of Education (N.T.J.), and Department of Health and Human Development, College of Family and Consumer Sciences (O.A.), University of Georgia, Athens, Georgia 30602; and Department of Neuroscience and Regenerative Medicine (C.I.), and Department of Cellular Biology and Anatomy (M.H.), Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912.
authors.forename: R D
authors.initials: RD
authors.lastname: Lewis
mesh_terms: D015502:Absorptiometry, Photon; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000502:physiology; D001827:Body Height; D015519:Bone Density / Q000502:physiology*; D002648:Child; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008572:Menarche; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000502:physiology*
chemical_list: D001786:Blood Glucose; C583557:IGF1 protein, human; D007328:Insulin; D007334:Insulin-Like Growth Factor I