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Published in: BMC Endocrine Disorders 1/2020

01-12-2020 | Insulins | Research article

Relationship between hemoglobin and insulin-like growth factor-1 in children and adolescents with idiopathic short stature

Authors: Qianqian Zhao, Mei Zhang, Baolan Ji, Yuntian Chu, Hui Pan, Wenhua Yan, Bo Ban

Published in: BMC Endocrine Disorders | Issue 1/2020

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Abstract

Background

The growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis is critical for the regulation of children’s growth and development. Serum IGF-1 concentrations are usually low in individuals with idiopathic short stature (ISS) despite normal endogenous GH levels, and the associated underlying factors are unknown. This study aimed to explore the relationship between IGF-1 and hemoglobin (Hb) in children with ISS.

Methods

A cross-sectional analysis was performed including 178 children and adolescents with ISS who were enrolled from March 2013 to February 2019. The related clinical and biochemical parameters were evaluated for each patient. Univariate analysis, smooth curve fitting and multivariate piecewise linear regression were performed.

Result

The mean levels of IGF-1 standard deviation scores (SDS) and Hb were − 0.99 (− 1.60 - -0.09) and 131.81 ± 9.36 g/L, respectively. Univariate analysis displayed a significant positive association between Hb and IGF-1 SDS (P < 0.001). After adjusting for potential confounding factors, the positive relationship between Hb and IGF-1 SDS remained (P = 0.001). Furthermore, there was an inflection point for Hb in the curve. In a multivariate piecewise linear regression model, IGF-1 SDS was significantly positively associated with Hb when Hb concentrations were lower than 145 g/L (B 0.05; 95% CI 0.02, 0.07; P < 0.001). However, IGF-1 SDS decreased with increasing Hb levels when Hb concentrations were greater than 145 g/L (B -0.15; 95% CI -0.23, − 0.06; P = 0.001).

Conclusion

This study demonstrated that Hb is associated with IGF-1 in Chinese children and adolescents with ISS. The levels of IGF-1 increased with the elevation of Hb, but when the concentration of Hb exceeded a certain range, with the increase of Hb, IGF-1 decreased instead.
Literature
1.
go back to reference Cohen P, Rogol AD, Deal CL, Saenger P, Reiter EO, Ross JL, Chernausek SD, Savage MO, Wit JM. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the growth hormone research society, the Lawson Wilkins pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop. J Clin Endocrinol Metab. 2008;93(11):4210–7.PubMedCrossRef Cohen P, Rogol AD, Deal CL, Saenger P, Reiter EO, Ross JL, Chernausek SD, Savage MO, Wit JM. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the growth hormone research society, the Lawson Wilkins pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop. J Clin Endocrinol Metab. 2008;93(11):4210–7.PubMedCrossRef
2.
go back to reference Derraik JGB, Miles HL, Chiavaroli V, Hofman PL, Cutfield WS. Idiopathic short stature and growth hormone sensitivity in prepubertal children. Clin Endocrinol. 2019;91(1):110–7. Derraik JGB, Miles HL, Chiavaroli V, Hofman PL, Cutfield WS. Idiopathic short stature and growth hormone sensitivity in prepubertal children. Clin Endocrinol. 2019;91(1):110–7.
3.
go back to reference Inzaghi E, Reiter E, Cianfarani S. The challenge of defining and investigating the causes of idiopathic short stature and finding an effective therapy. Horm Res Paediatr. 2019;92(2):71–83.PubMedCrossRef Inzaghi E, Reiter E, Cianfarani S. The challenge of defining and investigating the causes of idiopathic short stature and finding an effective therapy. Horm Res Paediatr. 2019;92(2):71–83.PubMedCrossRef
4.
go back to reference Stawerska R, Czkwianianc E, Smyczyńska J, Hilczer M, Lewiński A. Nutritional status in short stature children is related to both ghrelin and insulin-like growth factor I concentrations. J Pediatr Gastroenterol Nutr. 2017;64(5):812–7.PubMedCrossRef Stawerska R, Czkwianianc E, Smyczyńska J, Hilczer M, Lewiński A. Nutritional status in short stature children is related to both ghrelin and insulin-like growth factor I concentrations. J Pediatr Gastroenterol Nutr. 2017;64(5):812–7.PubMedCrossRef
5.
go back to reference Kumar A, Pal A, Kalaivani M, Gupta N, Jain V. Etiology of short stature in Indian children and an assessment of the growth hormone-insulin-like growth factor axis in children with idiopathic short stature. J Pediatr Endocrinol Metab. 2018;31(9):1009–17.PubMedCrossRef Kumar A, Pal A, Kalaivani M, Gupta N, Jain V. Etiology of short stature in Indian children and an assessment of the growth hormone-insulin-like growth factor axis in children with idiopathic short stature. J Pediatr Endocrinol Metab. 2018;31(9):1009–17.PubMedCrossRef
6.
go back to reference Wang P, Ji B, Shao Q, Zhang M, Ban B. Association between insulin-like growth Factor-1 and uric acid in Chinese children and adolescents with idiopathic short stature: a cross-sectional study. Biomed Res Int. 2018;2018:1–6. Wang P, Ji B, Shao Q, Zhang M, Ban B. Association between insulin-like growth Factor-1 and uric acid in Chinese children and adolescents with idiopathic short stature: a cross-sectional study. Biomed Res Int. 2018;2018:1–6.
7.
go back to reference Zhao Q, Jiang Y, Zhang M, Chu Y, Ji B, Pan H, Ban B. Low-density lipoprotein cholesterol levels are associated with insulin-like growth factor-1 in short-stature children and adolescents: a cross-sectional study. Lipids Health Dis. 2019;18:120.PubMedPubMedCentralCrossRef Zhao Q, Jiang Y, Zhang M, Chu Y, Ji B, Pan H, Ban B. Low-density lipoprotein cholesterol levels are associated with insulin-like growth factor-1 in short-stature children and adolescents: a cross-sectional study. Lipids Health Dis. 2019;18:120.PubMedPubMedCentralCrossRef
8.
go back to reference Larson LM, Kubes JN, Ramírez Luzuriaga MJ, Khishen S. H. Shankar a, Prado EL. Effects of increased hemoglobin on child growth, development, and disease: a systematic review and meta-analysis. Ann N Y Acad Sci. 2019;1450(1):83–104.PubMed Larson LM, Kubes JN, Ramírez Luzuriaga MJ, Khishen S. H. Shankar a, Prado EL. Effects of increased hemoglobin on child growth, development, and disease: a systematic review and meta-analysis. Ann N Y Acad Sci. 2019;1450(1):83–104.PubMed
9.
go back to reference Choy CC, Desai MM, Park JJ, Frame EA, Thompson AA, Naseri T, Reupena MS, Duckham RL, Deziel NC, Hawley NL. Child, maternal and household-level correlates of nutritional status: a cross-sectional study among young Samoan children. Public Health Nutr. 2017;20:1235–47.PubMedCrossRef Choy CC, Desai MM, Park JJ, Frame EA, Thompson AA, Naseri T, Reupena MS, Duckham RL, Deziel NC, Hawley NL. Child, maternal and household-level correlates of nutritional status: a cross-sectional study among young Samoan children. Public Health Nutr. 2017;20:1235–47.PubMedCrossRef
10.
go back to reference AT S, De Sanctis V, S K. Anemia and growth. Indian J Endocrinol Metab. 2014;18:S1–5. AT S, De Sanctis V, S K. Anemia and growth. Indian J Endocrinol Metab. 2014;18:S1–5.
11.
go back to reference Kajimura S, Aida K, Duan C. Insulin-like growth factor-binding protein-1 (IGFBP-1) mediates hypoxia-induced embryonic growth and developmental retardation. Proc Natl Acad Sci U S A. 2005;102:1240–5.PubMedPubMedCentralCrossRef Kajimura S, Aida K, Duan C. Insulin-like growth factor-binding protein-1 (IGFBP-1) mediates hypoxia-induced embryonic growth and developmental retardation. Proc Natl Acad Sci U S A. 2005;102:1240–5.PubMedPubMedCentralCrossRef
12.
go back to reference Soliman AT, De Sanctis V, Yassin M, Adel A. Growth and growth hormone - insulin like growth factor -I (GH-IGF-I) Axis in chronic Anemias. Acta Biomed. 2017;88(1):101–11.PubMed Soliman AT, De Sanctis V, Yassin M, Adel A. Growth and growth hormone - insulin like growth factor -I (GH-IGF-I) Axis in chronic Anemias. Acta Biomed. 2017;88(1):101–11.PubMed
13.
go back to reference Shimizu Y, Nakazato M, Sekita T, Kadota K, Arima K, Yamasaki H, Takamura N, Aoyagi K, Maeda T. Association between the hemoglobin levels and hypertension in relation to the BMI status in a rural Japanese population: the Nagasaki Islands study. Intern Med. 2014;53(5):435–40.PubMedCrossRef Shimizu Y, Nakazato M, Sekita T, Kadota K, Arima K, Yamasaki H, Takamura N, Aoyagi K, Maeda T. Association between the hemoglobin levels and hypertension in relation to the BMI status in a rural Japanese population: the Nagasaki Islands study. Intern Med. 2014;53(5):435–40.PubMedCrossRef
14.
go back to reference Shimizu Y, Nakazato M, Sekita T, Kadota K, Yamasaki H, Takamura N, Aoyagi K, Maeda T. Association between hemoglobin levels and arterial stiffness for general Japanese population in relation to body mass index status: the Nagasaki Islands study. Geriatr Gerontol Int. 2014;14(4):811–8.PubMedCrossRef Shimizu Y, Nakazato M, Sekita T, Kadota K, Yamasaki H, Takamura N, Aoyagi K, Maeda T. Association between hemoglobin levels and arterial stiffness for general Japanese population in relation to body mass index status: the Nagasaki Islands study. Geriatr Gerontol Int. 2014;14(4):811–8.PubMedCrossRef
15.
go back to reference Dewey KG, Oaks BM. U-shaped curve for risk associated with maternal hemoglobin, iron status, or iron supplementation. Am J Clin Nutr. 2017;106(Suppl 6):1694S–702S.PubMedPubMedCentralCrossRef Dewey KG, Oaks BM. U-shaped curve for risk associated with maternal hemoglobin, iron status, or iron supplementation. Am J Clin Nutr. 2017;106(Suppl 6):1694S–702S.PubMedPubMedCentralCrossRef
16.
go back to reference Starr LM, Scott ME, Koski KG. Protein deficiency and intestinal nematode infection in pregnant mice differentially impact fetal growth through specific stress hormones, growth factors, and cytokines. J Nutr. 2015;145(1):41–50.PubMedCrossRef Starr LM, Scott ME, Koski KG. Protein deficiency and intestinal nematode infection in pregnant mice differentially impact fetal growth through specific stress hormones, growth factors, and cytokines. J Nutr. 2015;145(1):41–50.PubMedCrossRef
17.
go back to reference Succurro E, Arturi F, Caruso V, Rudi S, Sciacqua A, Andreozzi F, Hribal ML, Perticone F, Sesti G. Low insulin-like growth factor-1 levels are associated with anaemia in adult non-diabetic subjects. Thromb Haemost. 2011;105(2):365–70.PubMedCrossRef Succurro E, Arturi F, Caruso V, Rudi S, Sciacqua A, Andreozzi F, Hribal ML, Perticone F, Sesti G. Low insulin-like growth factor-1 levels are associated with anaemia in adult non-diabetic subjects. Thromb Haemost. 2011;105(2):365–70.PubMedCrossRef
18.
go back to reference Nilsson-Ehle H, Bengtsson BA, Lindstedt G, Mellstrom D. Insulin-like growth factor-1 is a predictor of blood haemoglobin concentration in 70-yr-old subjects. Eur J Haematol. 2005;74(2):111–6.PubMedCrossRef Nilsson-Ehle H, Bengtsson BA, Lindstedt G, Mellstrom D. Insulin-like growth factor-1 is a predictor of blood haemoglobin concentration in 70-yr-old subjects. Eur J Haematol. 2005;74(2):111–6.PubMedCrossRef
19.
go back to reference Utriainen P, Jaaskelainen J, Voutilainen R. Blood erythrocyte and hemoglobin concentrations in premature adrenarche. J Clin Endocrinol Metab. 2013;98(1):E87–91.PubMedCrossRef Utriainen P, Jaaskelainen J, Voutilainen R. Blood erythrocyte and hemoglobin concentrations in premature adrenarche. J Clin Endocrinol Metab. 2013;98(1):E87–91.PubMedCrossRef
20.
go back to reference Li H, Ji CY, Zong XN, Zhang YQ. Height and weight standardized growth charts for Chinese children and adolescents aged 0 to 18 years. Chinese J Pediatr. 2009;47(7):487–92. Li H, Ji CY, Zong XN, Zhang YQ. Height and weight standardized growth charts for Chinese children and adolescents aged 0 to 18 years. Chinese J Pediatr. 2009;47(7):487–92.
21.
go back to reference Wright CM, Ahmed L, Dunger DB, Preece MA, Cole TJ, Butler G. Can we characterise growth in puberty more accurately? Validation of a new puberty phase specific (PPS) growth chart. Arch Dis Child. 2012;97(Suppl 1):A100. Wright CM, Ahmed L, Dunger DB, Preece MA, Cole TJ, Butler G. Can we characterise growth in puberty more accurately? Validation of a new puberty phase specific (PPS) growth chart. Arch Dis Child. 2012;97(Suppl 1):A100.
22.
go back to reference Isojima T, Shimatsu A, Yokoya S, Chihara K, Tanaka T, Hizuka N, Teramoto A, Tatsumi KI, Tachibana K, Katsumata N. Standardized centile curves and reference intervals of serum insulin-like growth factor-I (IGF-I) levels in a normal Japanese population using the LMS method. Endocr J. 2012;59(9):771–80.PubMedCrossRef Isojima T, Shimatsu A, Yokoya S, Chihara K, Tanaka T, Hizuka N, Teramoto A, Tatsumi KI, Tachibana K, Katsumata N. Standardized centile curves and reference intervals of serum insulin-like growth factor-I (IGF-I) levels in a normal Japanese population using the LMS method. Endocr J. 2012;59(9):771–80.PubMedCrossRef
23.
go back to reference Allali S, Brousse V, Sacri AS, Chalumeau M, de Montalembert M. Anemia in children: prevalence, causes, diagnostic work-up, and long-term consequences. Expert Rev Hematol. 2017;10(11):1023–8.PubMedCrossRef Allali S, Brousse V, Sacri AS, Chalumeau M, de Montalembert M. Anemia in children: prevalence, causes, diagnostic work-up, and long-term consequences. Expert Rev Hematol. 2017;10(11):1023–8.PubMedCrossRef
24.
go back to reference Wang Q, Liu DY, Yang LQ, Liu Y, Chen XJ. The epidemic characteristics of short stature in school students. Ital J Pediatr. 2015;41(1):1–6.CrossRef Wang Q, Liu DY, Yang LQ, Liu Y, Chen XJ. The epidemic characteristics of short stature in school students. Ital J Pediatr. 2015;41(1):1–6.CrossRef
25.
go back to reference De Vita F, Maggio M, Lauretani F, Crucitti L, Bandinelli S, Mammarella F, Landi F, Ferrucci L, Ceda GP. Insulin-like growth FACTOR-1 and anemia in older subjects: the INCHIANTI study. Endocr Pract. 2015;21(11):1211–8.PubMedPubMedCentralCrossRef De Vita F, Maggio M, Lauretani F, Crucitti L, Bandinelli S, Mammarella F, Landi F, Ferrucci L, Ceda GP. Insulin-like growth FACTOR-1 and anemia in older subjects: the INCHIANTI study. Endocr Pract. 2015;21(11):1211–8.PubMedPubMedCentralCrossRef
26.
go back to reference Vihervuori E, Virtanen M, Koistinen H, Koistinen R, Seppala M, Siimes MA. Hemoglobin level is linked to growth hormone-dependent proteins in short children. Blood. 1996;87(5):2075–81.PubMedCrossRef Vihervuori E, Virtanen M, Koistinen H, Koistinen R, Seppala M, Siimes MA. Hemoglobin level is linked to growth hormone-dependent proteins in short children. Blood. 1996;87(5):2075–81.PubMedCrossRef
27.
go back to reference Isguven P, Arslanoglu I, Erol M, Yildiz M, Adal E, Erguven M. Serum levels of ghrelin, leptin, IGF-I, IGFBP-3, insulin, thyroid hormones and cortisol in prepubertal children with iron deficiency. Endocr J. 2007;54(6):985–90.PubMedCrossRef Isguven P, Arslanoglu I, Erol M, Yildiz M, Adal E, Erguven M. Serum levels of ghrelin, leptin, IGF-I, IGFBP-3, insulin, thyroid hormones and cortisol in prepubertal children with iron deficiency. Endocr J. 2007;54(6):985–90.PubMedCrossRef
28.
go back to reference Soliman A, Eldabbagh M, Adel A, Sabt A. 765 linear growth and circulating IGF-I concentrations in children with Iron deficiency Anemia after treatment. Arch Dis Child. 2012;97(Suppl 2):A220.CrossRef Soliman A, Eldabbagh M, Adel A, Sabt A. 765 linear growth and circulating IGF-I concentrations in children with Iron deficiency Anemia after treatment. Arch Dis Child. 2012;97(Suppl 2):A220.CrossRef
29.
go back to reference Tsunawaki T, Sakai K, Momomura M, Wachi Y, Matsuzawa Y, Iwashita M. Hypoxia alters phosphorylation status of insulin-like growth factor (IGF)-binding protein-1 and attenuates biological activities of IGF-I in HepG2 cell cultures. J Obstet Gynaecol Res. 2013;39(9):1367–73.PubMedCrossRef Tsunawaki T, Sakai K, Momomura M, Wachi Y, Matsuzawa Y, Iwashita M. Hypoxia alters phosphorylation status of insulin-like growth factor (IGF)-binding protein-1 and attenuates biological activities of IGF-I in HepG2 cell cultures. J Obstet Gynaecol Res. 2013;39(9):1367–73.PubMedCrossRef
30.
go back to reference Tran PV, Fretham SJ, Wobken J, Miller BS, Georgieff MK. Gestational-neonatal iron deficiency suppresses and iron treatment reactivates IGF signaling in developing rat hippocampus. Am J Physiol Endocrinol Metab. 2012;302(3):E316–24.PubMedCrossRef Tran PV, Fretham SJ, Wobken J, Miller BS, Georgieff MK. Gestational-neonatal iron deficiency suppresses and iron treatment reactivates IGF signaling in developing rat hippocampus. Am J Physiol Endocrinol Metab. 2012;302(3):E316–24.PubMedCrossRef
Metadata
Title
Relationship between hemoglobin and insulin-like growth factor-1 in children and adolescents with idiopathic short stature
Authors
Qianqian Zhao
Mei Zhang
Baolan Ji
Yuntian Chu
Hui Pan
Wenhua Yan
Bo Ban
Publication date
01-12-2020
Publisher
BioMed Central
Keywords
Insulins
Insulins
Published in
BMC Endocrine Disorders / Issue 1/2020
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-020-00600-w

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