Insulin Resistance Negatively Influences the Muscle-Dependent IGF-1-Bone Mass Relationship in Premenarcheal Girls
J M Kindler1, N K Pollock1, E M Laing1
1Department 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.
Context:
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.
Design, Setting, And Participants:
This was a cross-sectional study conducted at a university research center involving 147 girls ages 9 to 11 years.
Main Outcome Measures:
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.
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