Carbohydrate metabolism during long-term growth hormone treatment in children with short stature born small for gestational age.
OBJECTIVE
To assess possible side-effects of long-term continuous growth hormone (GH) treatment on carbohydrate (CH) metabolism in children with short stature born small for gestational age.


METHODS
In a prospective, randomised double-blind, dose-response multicentre trial, the effect of GH treatment on CH metabolism was evaluated, comparing two GH dosages [3 vs. 6 IU/(m(2) body surface.day)].


METHODS
Seventy-eight children with short stature (height SD-score < - 1.88) born small for gestational age (birth length SD-score < - 1.88) being all prepubertal with a mean (SD) chronological age of 7.3 (2.2) years before start of treatment.


METHODS
Glucose and insulin concentrations during oral glucose tolerance tests (OGTTs) and glycosylated haemoglobin (HbA(1c)) were measured before and during 6 years of GH treatment.


RESULTS
Before treatment, the glucose response to oral glucose after 120 min was in six of the 78 children (8%) above 7.8 mmol/l but below 11.1 mmol/l, indicating impaired glucose tolerance (IGT), whereas after 6 years of GH treatment, IGT was found in 4% of the children. None of the children developed diabetes mellitus. Mean fasting glucose levels had increased significantly by 0.5 mmol/l after 1 year of GH treatment, without a further increase thereafter. The 2-h area under the curve adjusted for fasting levels (AUCab) for glucose and the HbA(1c) levels were lower after 6 years of GH treatment compared to baseline. During GH treatment, all HbA(1c) levels were in the normal range. In contrast to the effects on glucose levels, GH treatment induced considerably higher fasting insulin levels and glucose-stimulated insulin levels. The increase in AUCab for insulin occurred particularly during the first year of treatment, whereas the fasting insulin levels showed a further increase from one to six years. As a result, the 30- and 120-min ratios of insulin to glucose were higher during GH treatment compared to the start of treatment. The children who remained prepubertal during the entire study period showed similar patterns in glucose and insulin levels compared to the children who entered puberty. None of the observed changes were different between the GH dosage groups.


CONCLUSIONS
Continuous GH treatment during 6 years in children with short stature born small for gestational age has no adverse effects on glucose levels, even with dosages up to 6 IU/(m(2) d). However, as has been reported in other patient groups, GH treatment induces higher fasting insulin levels and glucose-stimulated insulin levels, indicating relative insulin resistance. Since the consequences of long-term hyperinsulinism during childhood are unknown, careful follow-up of these GH-treated children born small for gestational age is required.
Sas
T
T
Department of Paediatrics, Division of Endocrinology, Sophia Children's Hospital/Erasmus University, Rotterdam, The Netherlands.
Mulder
P
P
Aanstoot
H J
HJ
Houdijk
M
M
Jansen
M
M
Reeser
M
M
Hokken-Koelega
A
A
D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D050260:Carbohydrate Metabolism; D002648:Child; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D006130:Growth Disorders / Q000188:drug therapy / Q000378:metabolism*; D013006:Growth Hormone / Q000008:administration & dosage* / Q000627:therapeutic use; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008297:Male
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D013006:Growth Hormone; D019382:Human Growth Hormone; D007328:Insulin