Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years

Joseph M. Kindler; Norman K. Pollock; Emma M. Laing; Assaf Oshri; Nathan T. Jenkins; Carlos M. Isales; Mark W. Hamrick; Ke Hong Ding; Dorothy B. Hausman; George P. McCabe; Berdine R. Martin; Kathleen M. Hill Gallant; Stuart J. Warden; Connie M. Weaver; Munro Peacock; Richard D. Lewis

doi:10.1002/jbmr.3132

Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years

Joseph M. Kindler, Norman K. Pollock, Emma M. Laing, Assaf Oshri, Nathan T. Jenkins, Carlos M. Isales, Mark W. Hamrick, Ke Hong Ding, Dorothy B. Hausman, George P. McCabe, Berdine R. Martin, Kathleen M. Hill Gallant, Stuart J. Warden, Connie M. Weaver, Munro Peacock, Richard D. Lewis

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (p_Interaction < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (β_{Indirect Effect}= 0.321, p < 0.001). However, this relationship was moderated in the children with high (β_{Indirect Effect}= 0.200, p < 0.001) versus normal (β_{Indirect Effect}= 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed.

Original language	English (US)
Pages (from-to)	1537-1545
Number of pages	9
Journal	Journal of Bone and Mineral Research
Volume	32
Issue number	7
DOIs	https://doi.org/10.1002/jbmr.3132
State	Published - Jul 2017

Keywords

BONE QCT/µCT
GH/IGF-I
SKELETAL MUSCLE
pQCT

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Orthopedics and Sports Medicine

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Kindler, J. M., Pollock, N. K., Laing, E. M., Oshri, A., Jenkins, N. T., Isales, C. M., Hamrick, M. W., Ding, K. H., Hausman, D. B., McCabe, G. P., Martin, B. R., Hill Gallant, K. M., Warden, S. J., Weaver, C. M., Peacock, M., & Lewis, R. D. (2017). Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years. Journal of Bone and Mineral Research, 32(7), 1537-1545. https://doi.org/10.1002/jbmr.3132

Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years. / Kindler, Joseph M.; Pollock, Norman K.; Laing, Emma M.; Oshri, Assaf; Jenkins, Nathan T.; Isales, Carlos M.; Hamrick, Mark W.; Ding, Ke Hong; Hausman, Dorothy B.; McCabe, George P.; Martin, Berdine R.; Hill Gallant, Kathleen M.; Warden, Stuart J.; Weaver, Connie M.; Peacock, Munro; Lewis, Richard D.

In: Journal of Bone and Mineral Research, Vol. 32, No. 7, 07.2017, p. 1537-1545.

Research output: Contribution to journal › Article › peer-review

Kindler, JM, Pollock, NK, Laing, EM, Oshri, A, Jenkins, NT, Isales, CM , Hamrick, MW , Ding, KH, Hausman, DB, McCabe, GP, Martin, BR, Hill Gallant, KM, Warden, SJ, Weaver, CM, Peacock, M & Lewis, RD 2017, 'Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years', Journal of Bone and Mineral Research, vol. 32, no. 7, pp. 1537-1545. https://doi.org/10.1002/jbmr.3132

Kindler, Joseph M. ; Pollock, Norman K. ; Laing, Emma M. ; Oshri, Assaf ; Jenkins, Nathan T. ; Isales, Carlos M. ; Hamrick, Mark W. ; Ding, Ke Hong ; Hausman, Dorothy B. ; McCabe, George P. ; Martin, Berdine R. ; Hill Gallant, Kathleen M. ; Warden, Stuart J. ; Weaver, Connie M. ; Peacock, Munro ; Lewis, Richard D. / Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years. In: Journal of Bone and Mineral Research. 2017 ; Vol. 32, No. 7. pp. 1537-1545.

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title = "Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years",

abstract = "IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (pInteraction < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (βIndirect Effect= 0.321, p < 0.001). However, this relationship was moderated in the children with high (βIndirect Effect= 0.200, p < 0.001) versus normal (βIndirect Effect= 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed.",

keywords = "BONE QCT/µCT, GH/IGF-I, SKELETAL MUSCLE, pQCT",

author = "Kindler, {Joseph M.} and Pollock, {Norman K.} and Laing, {Emma M.} and Assaf Oshri and Jenkins, {Nathan T.} and Isales, {Carlos M.} and Hamrick, {Mark W.} and Ding, {Ke Hong} and Hausman, {Dorothy B.} and McCabe, {George P.} and Martin, {Berdine R.} and {Hill Gallant}, {Kathleen M.} and Warden, {Stuart J.} and Weaver, {Connie M.} and Munro Peacock and Lewis, {Richard D.}",

note = "Funding Information: We thank Ms Jessica Smith, the staff and students at the University of Georgia, Purdue University, and Indiana University who were involved in this study, as well as the participants and their families for their commitment to this research. This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development grant RO1HD057126, by the Allen Foundation grant 2.008.319, and by the University of Georgia Agricultural Experiment Station, HATCH projects GEO00797 and GEO00700. ClinicalTrials.gov Identifier: NCT00931580. Authors? roles: Study design: JMK, EML, NKP, AO, and RDL. Study conduct: all authors. Data collection: JMK, EML, RDL, CMI, and KHD. Data interpretation: all authors. Drafting manuscript: JMK. Revising manuscript content: all authors. Approving final version of manuscript: all authors. JMK and RDL take responsibility for the integrity of the data analysis. Publisher Copyright: {\textcopyright} 2017 American Society for Bone and Mineral Research Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",

year = "2017",

month = jul,

doi = "10.1002/jbmr.3132",

language = "English (US)",

volume = "32",

pages = "1537--1545",

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T1 - Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years

AU - Kindler, Joseph M.

AU - Pollock, Norman K.

AU - Laing, Emma M.

AU - Oshri, Assaf

AU - Jenkins, Nathan T.

AU - Isales, Carlos M.

AU - Hamrick, Mark W.

AU - Ding, Ke Hong

AU - Hausman, Dorothy B.

AU - McCabe, George P.

AU - Martin, Berdine R.

AU - Hill Gallant, Kathleen M.

AU - Warden, Stuart J.

AU - Weaver, Connie M.

AU - Peacock, Munro

AU - Lewis, Richard D.

N1 - Funding Information: We thank Ms Jessica Smith, the staff and students at the University of Georgia, Purdue University, and Indiana University who were involved in this study, as well as the participants and their families for their commitment to this research. This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development grant RO1HD057126, by the Allen Foundation grant 2.008.319, and by the University of Georgia Agricultural Experiment Station, HATCH projects GEO00797 and GEO00700. ClinicalTrials.gov Identifier: NCT00931580. Authors? roles: Study design: JMK, EML, NKP, AO, and RDL. Study conduct: all authors. Data collection: JMK, EML, RDL, CMI, and KHD. Data interpretation: all authors. Drafting manuscript: JMK. Revising manuscript content: all authors. Approving final version of manuscript: all authors. JMK and RDL take responsibility for the integrity of the data analysis. Publisher Copyright: © 2017 American Society for Bone and Mineral Research Copyright: Copyright 2018 Elsevier B.V., All rights reserved.

PY - 2017/7

Y1 - 2017/7

N2 - IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (pInteraction < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (βIndirect Effect= 0.321, p < 0.001). However, this relationship was moderated in the children with high (βIndirect Effect= 0.200, p < 0.001) versus normal (βIndirect Effect= 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed.

AB - IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (pInteraction < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (βIndirect Effect= 0.321, p < 0.001). However, this relationship was moderated in the children with high (βIndirect Effect= 0.200, p < 0.001) versus normal (βIndirect Effect= 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed.

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KW - GH/IGF-I

KW - SKELETAL MUSCLE

KW - pQCT

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Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years

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