Insulin resistance negatively influences the muscle- dependent igf-1-bone mass relationship in premenarcheal girls

J. M. Kindler, Norman K. Pollock, E. M. Laing, N. T. Jenkins, A. Oshri, Carlos M Isales, Mark W Hamrick, R. D. Lewis

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 dualenergy 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.

Original languageEnglish (US)
Pages (from-to)199-205
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume101
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

Insulin-Like Growth Factor I
Muscle
Insulin Resistance
Bone
Insulin
Bone and Bones
Muscles
Bone Density
Minerals
Fats
Tissue
Homeostasis
Bone Development
Cell signaling
Glucose
Muscle Development
Fasting
Skeletal Muscle
Blood
Cross-Sectional Studies

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Insulin resistance negatively influences the muscle- dependent igf-1-bone mass relationship in premenarcheal girls. / Kindler, J. M.; Pollock, Norman K.; Laing, E. M.; Jenkins, N. T.; Oshri, A.; Isales, Carlos M; Hamrick, Mark W; Lewis, R. D.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 101, No. 1, 01.01.2016, p. 199-205.

Research output: Contribution to journalArticle

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AU - Jenkins, N. T.

AU - Oshri, A.

AU - Isales, Carlos M

AU - Hamrick, Mark W

AU - Lewis, R. D.

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AB - 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 dualenergy 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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