Elsevier

The Journal of Pediatrics

Volume 142, Issue 2, February 2003, Pages 113-116
The Journal of Pediatrics

Original Articles
Reduced insulin sensitivity during growth hormone therapy for short children born small for gestational age☆,☆☆

https://doi.org/10.1067/mpd.2003.8Get rights and content

Abstract

Objectives To examine the influence of recombinant human growth hormone (rhGH) therapy on insulin sensitivity in short children born small for gestational age (SGA). Study design Twelve short (height standard deviation score, −3.2 ± 0.1) non–GH-deficient children SGA (7 boys/5 girls) were studied at 9.3 ± 1.0 years of age. The insulin sensitivity index was measured with Bergman's minimal model before (11 children) and during (12 children) rhGH therapy (21 ± 6 months) administered daily at 20 IU/m2 per week. No child had a change in pubertal status during the study. In addition, 5 children who remained prepubertal had insulin sensitivity remeasured 3 months after rhGH therapy was suspended. Results With rhGH therapy, insulin sensitivity fell 44% ± 10% (P =.018), with a compensatory rise in the acute insulin response of 123% ± 59% (P <.009). Reassessment of insulin sensitivity in 5 children (3 boys/2 girls) 3 months after suspension of rhGH occurred at 9.9 ± 0.7 years. Insulin sensitivity remained unchanged after rhGH therapy was stopped: 31.6 (20.5-42.3) before treatment, 11.5 (5.7-24.4) with treatment, and 10.7 (6.2-16.9) 10−4 · min−1 μU/mL after treatment. Conclusions Children SGA are known to have reduced insulin sensitivity. There was a further reduction in insulin sensitivity with rhGH therapy that did not recover 3 months after rhGH therapy was stopped. (J Pediatr 2003;142:113-6)

Section snippets

Patients

All children were born SGA and had marked short stature (height approximately −3 SDS) with a height velocity <25th percentile for >1 year before starting rhGH therapy.8 SGA was defined as a birth weight <10th percentile for gestational age.9 Additional enrollment criteria for inclusion into the study included no change in Tanner pubertal stage and/or testicular volumes throughout the study period, normal GH response to clonidine stimulation (defined as a GH level ≥7 μg/L), absence of both islet

Results

Seven boys and 5 girls were studied. Three children were in early puberty (Tanner stage 2 breast development or testicular volumes <6 mL) on both occasions when insulin sensitivity was measured. All other children remained prepubertal, as earlier defined, throughout the study period. At enrollment, children were 9.3 ± 1.0 years old, of white ethnicity (11 of 12 children), with a birth weight SDS of −3.5 ± 0.7 and pretreatment height SDS of −3.2 ± 0.1. Children received 21 ± 6 months of rhGH

Discussion

We previously demonstrated that short children born SGA had reduced insulin sensitivity when matched to short normal children.7 We now show that during rhGH treatment of children SGA with short stature, there is a further reduction in insulin sensitivity that persists 3 months after rhGH is stopped. The reduction in insulin sensitivity was accompanied by a compensatory increase in insulin secretion, as reflected in the AIR, to maintain euglycemia.

rhGH induces anti-insulin effects through

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      Therefore, our results do not support the hypothesis that higher insulin levels promote better growth. This is in accordance with the findings of Cutfield et al, who did not observe a relation between the fall in insulin sensitivity and change in relative height velocity.27 The reduction in insulin sensitivity was significant and could be seen in almost every individual child (Figure 1).

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    ☆

    Supported by grants from the Auckland Medical Research Foundation, Health Research Council of New Zealand, and Pharmacia Corporation.

    ☆☆

    Reprint requests: Wayne Cutfield, Department of Paediatrics, University of Auckland, Private Bag 92019, Auckland, New Zealand.

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