Prepubertal Children With Obesity Have High Free IGF-1 Levels and Accelerated Growth Despite Reduced Pappalysin Levels

Álvaro Martín-Rivada; Gabriel Martos-Moreno; Santiago Guerra-Cantera; Ana Campillo-Calatayud; Claus Oxvig; Jan Frystyk; Julie A. Chowen; Vicente Barrios; Jesús Argente

doi:10.1210/clinem/dgae288

Prepubertal Children With Obesity Have High Free IGF-1 Levels and Accelerated Growth Despite Reduced Pappalysin Levels

Álvaro Martín-Rivada
, Gabriel Martos-Moreno
, Santiago Guerra-Cantera
, Ana Campillo-Calatayud
, Claus Oxvig
, Jan Frystyk
, Julie A. Chowen
, Vicente Barrios
, Jesús Argente^*

^*Corresponding author af dette arbejde

Institut for Molekylærbiologi og Genetik

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

3 Citationer (Scopus)

Abstract

Background: Prepubertal children with obesity frequently have enhanced growth, accelerated skeletal maturation, and changes in the growth hormone-insulin-like growth factor (GH-IGF) axis. However, the involvement of pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC1, STC2) as regulators of IGF bioavailability has not been studied in obesity. Objective: We aimed to determine the effects of childhood obesity and weight reduction on serum levels of PAPP-A, PAPP-A2, STC1, and STC2 and their relationship with IGF bioavailability, growth, and other components of the GH-IGF system. Methods: Prepubertal children with severe obesity (150, 50% males/females, age: 7.72 ± 2.05 years, BMI z-score: 4.95 ± 1.70, height z-score: 1.28 ± 1.04) were studied at diagnosis and after a minimum of 0.5 BMI z-score reduction. Two hundred and six healthy age- and sex-matched children were used as controls. Results: Children with obesity had decreased serum concentrations of PAPP-A, PAPP-A2 and STC2, but increased total and free IGF-I, intact IGFBP-3, acid-labile subunit (ALS), IGF-II, and insulin levels, with no difference in the free IGF-I/total IGF-I ratio. Neither the standardized body mass index (BMI) nor height correlated with any biochemical parameter analyzed. A decrease in IGF-II, insulin, and ALS with an increase in IGFBP-2 and -5, STC2, and PAPP-A were observed after weight loss. Conclusion: Increased circulating total and free IGF-I, insulin, and IGF-II may all contribute to the increased rate of prepubertal growth and bone maturation observed in children with obesity, with STC2 possibly being involved.

Originalsprog	Engelsk
Tidsskrift	Journal of Clinical Endocrinology and Metabolism
Vol/bind	110
Nummer	3
Sider (fra-til)	e622-e629
ISSN	0021-972X
DOI	https://doi.org/10.1210/clinem/dgae288
Status	Udgivet - mar. 2025

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Martín-Rivada, Á., Martos-Moreno, G., Guerra-Cantera, S., Campillo-Calatayud, A., Oxvig, C., Frystyk, J., Chowen, J. A., Barrios, V., & Argente, J. (2025). Prepubertal Children With Obesity Have High Free IGF-1 Levels and Accelerated Growth Despite Reduced Pappalysin Levels. Journal of Clinical Endocrinology and Metabolism, 110(3), e622-e629. https://doi.org/10.1210/clinem/dgae288

@article{2b6cb5a7502742f3abf7f9c54db396d1,

title = "Prepubertal Children With Obesity Have High Free IGF-1 Levels and Accelerated Growth Despite Reduced Pappalysin Levels",

abstract = "Background: Prepubertal children with obesity frequently have enhanced growth, accelerated skeletal maturation, and changes in the growth hormone-insulin-like growth factor (GH-IGF) axis. However, the involvement of pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC1, STC2) as regulators of IGF bioavailability has not been studied in obesity. Objective: We aimed to determine the effects of childhood obesity and weight reduction on serum levels of PAPP-A, PAPP-A2, STC1, and STC2 and their relationship with IGF bioavailability, growth, and other components of the GH-IGF system. Methods: Prepubertal children with severe obesity (150, 50\% males/females, age: 7.72 ± 2.05 years, BMI z-score: 4.95 ± 1.70, height z-score: 1.28 ± 1.04) were studied at diagnosis and after a minimum of 0.5 BMI z-score reduction. Two hundred and six healthy age- and sex-matched children were used as controls. Results: Children with obesity had decreased serum concentrations of PAPP-A, PAPP-A2 and STC2, but increased total and free IGF-I, intact IGFBP-3, acid-labile subunit (ALS), IGF-II, and insulin levels, with no difference in the free IGF-I/total IGF-I ratio. Neither the standardized body mass index (BMI) nor height correlated with any biochemical parameter analyzed. A decrease in IGF-II, insulin, and ALS with an increase in IGFBP-2 and -5, STC2, and PAPP-A were observed after weight loss. Conclusion: Increased circulating total and free IGF-I, insulin, and IGF-II may all contribute to the increased rate of prepubertal growth and bone maturation observed in children with obesity, with STC2 possibly being involved.",

keywords = "children obesity, growth, IGF-I, IGFBP, pappalysin, stanniocalcin",

author = "{\'A}lvaro Mart{\'i}n-Rivada and Gabriel Martos-Moreno and Santiago Guerra-Cantera and Ana Campillo-Calatayud and Claus Oxvig and Jan Frystyk and Chowen, \{Julie A.\} and Vicente Barrios and Jes{\'u}s Argente",

year = "2025",

month = mar,

doi = "10.1210/clinem/dgae288",

language = "English",

volume = "110",

pages = "e622--e629",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Endocrine Society",

number = "3",

}

Martín-Rivada, Á, Martos-Moreno, G, Guerra-Cantera, S, Campillo-Calatayud, A, Oxvig, C, Frystyk, J, Chowen, JA, Barrios, V & Argente, J 2025, 'Prepubertal Children With Obesity Have High Free IGF-1 Levels and Accelerated Growth Despite Reduced Pappalysin Levels', Journal of Clinical Endocrinology and Metabolism, bind 110, nr. 3, s. e622-e629. https://doi.org/10.1210/clinem/dgae288

Prepubertal Children With Obesity Have High Free IGF-1 Levels and Accelerated Growth Despite Reduced Pappalysin Levels. / Martín-Rivada, Álvaro; Martos-Moreno, Gabriel; Guerra-Cantera, Santiago et al.
I: Journal of Clinical Endocrinology and Metabolism, Bind 110, Nr. 3, 03.2025, s. e622-e629.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Prepubertal Children With Obesity Have High Free IGF-1 Levels and Accelerated Growth Despite Reduced Pappalysin Levels

AU - Martín-Rivada, Álvaro

AU - Martos-Moreno, Gabriel

AU - Guerra-Cantera, Santiago

AU - Campillo-Calatayud, Ana

AU - Oxvig, Claus

AU - Frystyk, Jan

AU - Chowen, Julie A.

AU - Barrios, Vicente

AU - Argente, Jesús

PY - 2025/3

Y1 - 2025/3

N2 - Background: Prepubertal children with obesity frequently have enhanced growth, accelerated skeletal maturation, and changes in the growth hormone-insulin-like growth factor (GH-IGF) axis. However, the involvement of pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC1, STC2) as regulators of IGF bioavailability has not been studied in obesity. Objective: We aimed to determine the effects of childhood obesity and weight reduction on serum levels of PAPP-A, PAPP-A2, STC1, and STC2 and their relationship with IGF bioavailability, growth, and other components of the GH-IGF system. Methods: Prepubertal children with severe obesity (150, 50% males/females, age: 7.72 ± 2.05 years, BMI z-score: 4.95 ± 1.70, height z-score: 1.28 ± 1.04) were studied at diagnosis and after a minimum of 0.5 BMI z-score reduction. Two hundred and six healthy age- and sex-matched children were used as controls. Results: Children with obesity had decreased serum concentrations of PAPP-A, PAPP-A2 and STC2, but increased total and free IGF-I, intact IGFBP-3, acid-labile subunit (ALS), IGF-II, and insulin levels, with no difference in the free IGF-I/total IGF-I ratio. Neither the standardized body mass index (BMI) nor height correlated with any biochemical parameter analyzed. A decrease in IGF-II, insulin, and ALS with an increase in IGFBP-2 and -5, STC2, and PAPP-A were observed after weight loss. Conclusion: Increased circulating total and free IGF-I, insulin, and IGF-II may all contribute to the increased rate of prepubertal growth and bone maturation observed in children with obesity, with STC2 possibly being involved.

AB - Background: Prepubertal children with obesity frequently have enhanced growth, accelerated skeletal maturation, and changes in the growth hormone-insulin-like growth factor (GH-IGF) axis. However, the involvement of pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC1, STC2) as regulators of IGF bioavailability has not been studied in obesity. Objective: We aimed to determine the effects of childhood obesity and weight reduction on serum levels of PAPP-A, PAPP-A2, STC1, and STC2 and their relationship with IGF bioavailability, growth, and other components of the GH-IGF system. Methods: Prepubertal children with severe obesity (150, 50% males/females, age: 7.72 ± 2.05 years, BMI z-score: 4.95 ± 1.70, height z-score: 1.28 ± 1.04) were studied at diagnosis and after a minimum of 0.5 BMI z-score reduction. Two hundred and six healthy age- and sex-matched children were used as controls. Results: Children with obesity had decreased serum concentrations of PAPP-A, PAPP-A2 and STC2, but increased total and free IGF-I, intact IGFBP-3, acid-labile subunit (ALS), IGF-II, and insulin levels, with no difference in the free IGF-I/total IGF-I ratio. Neither the standardized body mass index (BMI) nor height correlated with any biochemical parameter analyzed. A decrease in IGF-II, insulin, and ALS with an increase in IGFBP-2 and -5, STC2, and PAPP-A were observed after weight loss. Conclusion: Increased circulating total and free IGF-I, insulin, and IGF-II may all contribute to the increased rate of prepubertal growth and bone maturation observed in children with obesity, with STC2 possibly being involved.

KW - children obesity

KW - growth

KW - IGF-I

KW - IGFBP

KW - pappalysin

KW - stanniocalcin

UR - https://www.scopus.com/pages/publications/85215664290

U2 - 10.1210/clinem/dgae288

DO - 10.1210/clinem/dgae288

M3 - Journal article

C2 - 38662803

AN - SCOPUS:85215664290

SN - 0021-972X

VL - 110

SP - e622-e629

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 3

ER -

Prepubertal Children With Obesity Have High Free IGF-1 Levels and Accelerated Growth Despite Reduced Pappalysin Levels

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