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. © 2017 American Society for Bone and Mineral Research.
authors.affiliation: Department of Foods and Nutrition, The University of Georgia, Athens, GA, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Kindler
authors.affiliation: Department of Pediatrics, Augusta University, Augusta, GA, USA.
authors.forename: Norman K
authors.initials: NK
authors.lastname: Pollock
authors.affiliation: Department of Foods and Nutrition, The University of Georgia, Athens, GA, USA.
authors.forename: Emma M
authors.initials: EM
authors.lastname: Laing
authors.affiliation: Department of Human Development and Family Science, The University of Georgia, Athens, GA, USA.
authors.forename: Assaf
authors.initials: A
authors.lastname: Oshri
authors.affiliation: Department of Kinesiology, The University of Georgia, Athens, GA, USA.
authors.forename: Nathan T
authors.initials: NT
authors.lastname: Jenkins
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Augusta University, Augusta, GA, USA.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Isales
authors.affiliation: Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Hamrick
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Augusta University, Augusta, GA, USA.
authors.forename: Ke-Hong
authors.initials: KH
authors.lastname: Ding
authors.affiliation: Department of Foods and Nutrition, The University of Georgia, Athens, GA, USA.
authors.forename: Dorothy B
authors.initials: DB
authors.lastname: Hausman
authors.affiliation: Department of Statistics, Purdue University, West Lafayette, IN, USA.
authors.forename: George P
authors.initials: GP
authors.lastname: McCabe
authors.affiliation: Department of Nutrition Science, Purdue University, West Lafayette, IN, USA.
authors.forename: Berdine R
authors.initials: BR
authors.lastname: Martin
authors.affiliation: Department of Nutrition Science, Purdue University, West Lafayette, IN, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Hill Gallant
authors.affiliation: Department of Physical Therapy, Indiana University, Indianapolis, IN, USA.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Warden
authors.affiliation: Department of Nutrition Science, Purdue University, West Lafayette, IN, USA.
authors.forename: Connie M
authors.initials: CM
authors.lastname: Weaver
authors.affiliation: Department of Medicine, Indiana University, Indianapolis, IN, USA.
authors.forename: Munro
authors.initials: M
authors.lastname: Peacock
authors.affiliation: Department of Foods and Nutrition, The University of Georgia, Athens, GA, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Lewis
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D015519:Bone Density; D002648:Child; D000071538:Cortical Bone / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D013977:Tibia / Q000000981:diagnostic imaging / Q000378:metabolism*; D014057:Tomography, X-Ray Computed
chemical_list: D001786:Blood Glucose; D007328:Insulin; D007334:Insulin-Like Growth Factor I
keywords: BONE QCT/µCT; GH/IGF-I; SKELETAL MUSCLE; pQCT