High-dose growth hormone (GH) treatment in non-GH-deficient children born small for gestational age induces growth responses related to pre-treatment GH secretion and associated with a reversible decrease in insulin sensitivity

Francis De Zegher, Ken Ong, Maria Van Helvoirt, Angelica Mohn, Kathryn (Katie) Woods, David Dunger

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Abstract

GH therapy variably reduces the height deficit of short children born small for gestational age (SGA) but is associated with hyperinsulinemia. Intermittent, higher-dose GH regimens may be alternatives to continuous, lower-dose treatment. We examined whether the growth response to GH therapy is related to pre-treatment indices of endogenous somatotropic activity, and studied the reversibility of the insulin resistant state induced by GH. 13 non-GH deficient short SGA children were randomised to high-dose GH (100 mcg/kg/day) by daily sc injection (n=9), or no GH treatment (n=4) for 2 years (2/4 controls subsequently received GH treatment). Overnight GH profiles were performed at baseline; intravenous glucose tolerance tests were performed at baseline, yearly on GH treatment, and 3 months post-GH treatment. Fasting glucose, insulin and proinsulin levels were measured, insulin sensitivity estimated using Bergman's minimal model, and glucose tolerance calculated from rate of glucose disappearance. In all GH-treated children, gain in height SDS (mean gain yr 1 = +1.2 SDS) was inversely related to baseline peak overnight GH (r=-0.88, n=10, p=0.0008), IGF-I (r=-0.74, n=11, p=0.009), and fasting insulin levels (r=-0.71, n=11, p=0.014). GH treatment increased fasting glucose (means: baseline vs. yr 2: 3.7 vs. 4.4 mmol/1, p=0.005), insulin (3.8 vs. 13.9 mU/1, p=0.0002), and proinsulin levels (1.7 vs. 4.5 pmol/1, p=0.004), and decreased insulin sensitivity (26.9 vs. 4.0 per min/mU/1×104, p=0.002). Glucose tolerance initially decreased (baseline: 2.62 min-1; Yr 1: 2.18, p=0.02; yr 2: 2.39, p=0.12). However, by 3 months post-GH treatment significant improvements were seen in fasting insulin (post-GH: 5.2 mU/1, p=0.0003 vs. Yr 2), proinsulin (1.7 pmol/1, p=0.002), and insulin sensitivity (17.6 per min/mU/1 × 104, p=0.0001). Post-GH treatment, fasting glucose levels (4.1 mmol/1, p=0.4) and glucose tolerance (2.49 min-1, p=0.4) were similar to baseline, and the slight increase in fasting insulin levels (5.2 mU/1, p=0.04) was similar to that observed in non-GH treated children over the 2 yr study period (baseline vs. 2 Years: 3.9 vs. 5.9 mU/1, n=4). In conclusion, in this study of 13 short non-GH-deficient SGA children, high-dose GH therapy induced growth responses that were associated with reversible decreases in insulin sensitivity, and that were predicted by pretreatment markers of endogenous, but not stimulated, somatotropic activity.

Original languageEnglish (US)
Pages (from-to)148-151
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume87
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

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Growth Hormone
Gestational Age
Insulin Resistance
Hormones
Insulin
Growth
Glucose
Fasting
Therapeutics
Proinsulin
Hyperinsulinism
Glucose Tolerance Test
Insulin-Like Growth Factor I

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

@article{f7b7899db6f048dd94f7c6e8eda43e9e,
title = "High-dose growth hormone (GH) treatment in non-GH-deficient children born small for gestational age induces growth responses related to pre-treatment GH secretion and associated with a reversible decrease in insulin sensitivity",
abstract = "GH therapy variably reduces the height deficit of short children born small for gestational age (SGA) but is associated with hyperinsulinemia. Intermittent, higher-dose GH regimens may be alternatives to continuous, lower-dose treatment. We examined whether the growth response to GH therapy is related to pre-treatment indices of endogenous somatotropic activity, and studied the reversibility of the insulin resistant state induced by GH. 13 non-GH deficient short SGA children were randomised to high-dose GH (100 mcg/kg/day) by daily sc injection (n=9), or no GH treatment (n=4) for 2 years (2/4 controls subsequently received GH treatment). Overnight GH profiles were performed at baseline; intravenous glucose tolerance tests were performed at baseline, yearly on GH treatment, and 3 months post-GH treatment. Fasting glucose, insulin and proinsulin levels were measured, insulin sensitivity estimated using Bergman's minimal model, and glucose tolerance calculated from rate of glucose disappearance. In all GH-treated children, gain in height SDS (mean gain yr 1 = +1.2 SDS) was inversely related to baseline peak overnight GH (r=-0.88, n=10, p=0.0008), IGF-I (r=-0.74, n=11, p=0.009), and fasting insulin levels (r=-0.71, n=11, p=0.014). GH treatment increased fasting glucose (means: baseline vs. yr 2: 3.7 vs. 4.4 mmol/1, p=0.005), insulin (3.8 vs. 13.9 mU/1, p=0.0002), and proinsulin levels (1.7 vs. 4.5 pmol/1, p=0.004), and decreased insulin sensitivity (26.9 vs. 4.0 per min/mU/1×104, p=0.002). Glucose tolerance initially decreased (baseline: 2.62 min-1; Yr 1: 2.18, p=0.02; yr 2: 2.39, p=0.12). However, by 3 months post-GH treatment significant improvements were seen in fasting insulin (post-GH: 5.2 mU/1, p=0.0003 vs. Yr 2), proinsulin (1.7 pmol/1, p=0.002), and insulin sensitivity (17.6 per min/mU/1 × 104, p=0.0001). Post-GH treatment, fasting glucose levels (4.1 mmol/1, p=0.4) and glucose tolerance (2.49 min-1, p=0.4) were similar to baseline, and the slight increase in fasting insulin levels (5.2 mU/1, p=0.04) was similar to that observed in non-GH treated children over the 2 yr study period (baseline vs. 2 Years: 3.9 vs. 5.9 mU/1, n=4). In conclusion, in this study of 13 short non-GH-deficient SGA children, high-dose GH therapy induced growth responses that were associated with reversible decreases in insulin sensitivity, and that were predicted by pretreatment markers of endogenous, but not stimulated, somatotropic activity.",
author = "{De Zegher}, Francis and Ken Ong and {Van Helvoirt}, Maria and Angelica Mohn and Woods, {Kathryn (Katie)} and David Dunger",
year = "2002",
doi = "10.1210/jc.87.1.148",
language = "English (US)",
volume = "87",
pages = "148--151",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "1",

}

TY - JOUR

T1 - High-dose growth hormone (GH) treatment in non-GH-deficient children born small for gestational age induces growth responses related to pre-treatment GH secretion and associated with a reversible decrease in insulin sensitivity

AU - De Zegher, Francis

AU - Ong, Ken

AU - Van Helvoirt, Maria

AU - Mohn, Angelica

AU - Woods, Kathryn (Katie)

AU - Dunger, David

PY - 2002

Y1 - 2002

N2 - GH therapy variably reduces the height deficit of short children born small for gestational age (SGA) but is associated with hyperinsulinemia. Intermittent, higher-dose GH regimens may be alternatives to continuous, lower-dose treatment. We examined whether the growth response to GH therapy is related to pre-treatment indices of endogenous somatotropic activity, and studied the reversibility of the insulin resistant state induced by GH. 13 non-GH deficient short SGA children were randomised to high-dose GH (100 mcg/kg/day) by daily sc injection (n=9), or no GH treatment (n=4) for 2 years (2/4 controls subsequently received GH treatment). Overnight GH profiles were performed at baseline; intravenous glucose tolerance tests were performed at baseline, yearly on GH treatment, and 3 months post-GH treatment. Fasting glucose, insulin and proinsulin levels were measured, insulin sensitivity estimated using Bergman's minimal model, and glucose tolerance calculated from rate of glucose disappearance. In all GH-treated children, gain in height SDS (mean gain yr 1 = +1.2 SDS) was inversely related to baseline peak overnight GH (r=-0.88, n=10, p=0.0008), IGF-I (r=-0.74, n=11, p=0.009), and fasting insulin levels (r=-0.71, n=11, p=0.014). GH treatment increased fasting glucose (means: baseline vs. yr 2: 3.7 vs. 4.4 mmol/1, p=0.005), insulin (3.8 vs. 13.9 mU/1, p=0.0002), and proinsulin levels (1.7 vs. 4.5 pmol/1, p=0.004), and decreased insulin sensitivity (26.9 vs. 4.0 per min/mU/1×104, p=0.002). Glucose tolerance initially decreased (baseline: 2.62 min-1; Yr 1: 2.18, p=0.02; yr 2: 2.39, p=0.12). However, by 3 months post-GH treatment significant improvements were seen in fasting insulin (post-GH: 5.2 mU/1, p=0.0003 vs. Yr 2), proinsulin (1.7 pmol/1, p=0.002), and insulin sensitivity (17.6 per min/mU/1 × 104, p=0.0001). Post-GH treatment, fasting glucose levels (4.1 mmol/1, p=0.4) and glucose tolerance (2.49 min-1, p=0.4) were similar to baseline, and the slight increase in fasting insulin levels (5.2 mU/1, p=0.04) was similar to that observed in non-GH treated children over the 2 yr study period (baseline vs. 2 Years: 3.9 vs. 5.9 mU/1, n=4). In conclusion, in this study of 13 short non-GH-deficient SGA children, high-dose GH therapy induced growth responses that were associated with reversible decreases in insulin sensitivity, and that were predicted by pretreatment markers of endogenous, but not stimulated, somatotropic activity.

AB - GH therapy variably reduces the height deficit of short children born small for gestational age (SGA) but is associated with hyperinsulinemia. Intermittent, higher-dose GH regimens may be alternatives to continuous, lower-dose treatment. We examined whether the growth response to GH therapy is related to pre-treatment indices of endogenous somatotropic activity, and studied the reversibility of the insulin resistant state induced by GH. 13 non-GH deficient short SGA children were randomised to high-dose GH (100 mcg/kg/day) by daily sc injection (n=9), or no GH treatment (n=4) for 2 years (2/4 controls subsequently received GH treatment). Overnight GH profiles were performed at baseline; intravenous glucose tolerance tests were performed at baseline, yearly on GH treatment, and 3 months post-GH treatment. Fasting glucose, insulin and proinsulin levels were measured, insulin sensitivity estimated using Bergman's minimal model, and glucose tolerance calculated from rate of glucose disappearance. In all GH-treated children, gain in height SDS (mean gain yr 1 = +1.2 SDS) was inversely related to baseline peak overnight GH (r=-0.88, n=10, p=0.0008), IGF-I (r=-0.74, n=11, p=0.009), and fasting insulin levels (r=-0.71, n=11, p=0.014). GH treatment increased fasting glucose (means: baseline vs. yr 2: 3.7 vs. 4.4 mmol/1, p=0.005), insulin (3.8 vs. 13.9 mU/1, p=0.0002), and proinsulin levels (1.7 vs. 4.5 pmol/1, p=0.004), and decreased insulin sensitivity (26.9 vs. 4.0 per min/mU/1×104, p=0.002). Glucose tolerance initially decreased (baseline: 2.62 min-1; Yr 1: 2.18, p=0.02; yr 2: 2.39, p=0.12). However, by 3 months post-GH treatment significant improvements were seen in fasting insulin (post-GH: 5.2 mU/1, p=0.0003 vs. Yr 2), proinsulin (1.7 pmol/1, p=0.002), and insulin sensitivity (17.6 per min/mU/1 × 104, p=0.0001). Post-GH treatment, fasting glucose levels (4.1 mmol/1, p=0.4) and glucose tolerance (2.49 min-1, p=0.4) were similar to baseline, and the slight increase in fasting insulin levels (5.2 mU/1, p=0.04) was similar to that observed in non-GH treated children over the 2 yr study period (baseline vs. 2 Years: 3.9 vs. 5.9 mU/1, n=4). In conclusion, in this study of 13 short non-GH-deficient SGA children, high-dose GH therapy induced growth responses that were associated with reversible decreases in insulin sensitivity, and that were predicted by pretreatment markers of endogenous, but not stimulated, somatotropic activity.

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