Skeletal growth and bone mineral acquisition in type 1 diabetic children; abnormalities of the GH/IGF-1 axis

Manish Raisingani, Brar Preneet, Brenda Kohn, Shoshana Yakar

Research output: Contribution to journalReview article

Abstract

Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases diagnosed in childhood. Childhood and adolescent years are also the most important period for growth in height and acquisition of skeletal bone mineral density (BMD). The growth hormone (GH)/insulin like growth factor -1 (IGF-1) axis which regulates growth, is affected by T1DM, with studies showing increased GH and decreased IGF-1 levels in children with T1DM. There is conflicting data as to whether adolescents with TIDM are able to achieve their genetically-determined adult height. Furthermore, data support that adolescents with T1DM have decreased peak BMD, although the pathophysiology of which has not been completely defined. Various mechanisms have been proposed for the decrease in BMD including low osteocalcin levels, reflecting decreased bone formation; increased sclerostin, an inhibitor of bone anabolic pathways; and increased leptin, an adipocytokine which affects bone metabolism via central and peripheral mechanisms. Other factors implicated in the increased bone resorption in T1DM include upregulation of the osteoprotegerin/ receptor-activator of the nuclear factor-κB ligand pathway, elevated parathyroid hormone levels, and activation of other cytokines involved in chronic systemic inflammation. In this review, we summarize the clinical studies that address the alterations in the GH/IGF-I axis, linear growth velocity, and BMD in children and adolescents with T1DM; and we review the possible molecular mechanisms that may contribute to an attenuation of linear growth and to the reduction in the acquisition of peak bone mass in the child and adolescent with T1DM.

Original languageEnglish (US)
Pages (from-to)13-21
Number of pages9
JournalGrowth Hormone and IGF Research
Volume34
DOIs
StatePublished - Jun 1 2017

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Bone Development
Somatomedins
Type 1 Diabetes Mellitus
Growth Hormone
Minerals
Bone Density
Growth
Bone and Bones
Osteoprotegerin
Adipokines
Osteocalcin
Bone Resorption
Cytoplasmic and Nuclear Receptors
Leptin
Parathyroid Hormone
Insulin-Like Growth Factor I
Osteogenesis
Chronic Disease
Up-Regulation
Cytokines

Keywords

  • Bone mineral density (BMD)
  • Growth hormone (GH)
  • Growth velocity
  • Insulin-like growth factor-1 (IGF-1)
  • Type 1 diabetes mellitus (T1DM)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Skeletal growth and bone mineral acquisition in type 1 diabetic children; abnormalities of the GH/IGF-1 axis. / Raisingani, Manish; Preneet, Brar; Kohn, Brenda; Yakar, Shoshana.

In: Growth Hormone and IGF Research, Vol. 34, 01.06.2017, p. 13-21.

Research output: Contribution to journalReview article

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