The exon 3-deleted/full-length growth hormone receptor polymorphism does not influence the effect of puberty or growth hormone therapy on glucose homeostasis in short non-growth hormone-deficient small-for-gestational-age children: results from a two-year controlled prospective study.
BACKGROUND
The exon 3-deleted/full-length (d3/fl) GH receptor polymorphism (d3/fl-GHR) has been associated with responsiveness to GH therapy in short small-for-gestational-age (SGA) patients, although consensus is lacking. However, its influence on glucose homeostasis, at baseline or under GH therapy, has not been investigated.


OBJECTIVE
Our objective was to evaluate whether the d3/fl-GHR genotypes influence insulin sensitivity in short SGA children before or after puberty onset or during GH therapy.


METHODS
We conducted a 2-yr prospective, controlled, randomized trial.


METHODS
Thirty Spanish hospitals participated. Auxological, GH secretion, and glucose homeostasis evaluation was hospital based, whereas molecular analyses and data computation were centralized.


METHODS
Patients included 219 short SGA children [body mass index sd score (SDS) < or = 2.0]; 159 were prepubertal (group 1), and 60 had entered puberty (group 2).


METHODS
Seventy-eight patients from group 1 were treated with GH (66 microg/kg.d) for 2 yr (group 3).


METHODS
Previous and 2-yr follow-up auxological and biochemical data were recorded, d3/fl-GHR genotypes determined, and data analyzed.


RESULTS
In groups 1 and 2, fasting glucose, insulin, homeostasis model assessment (HOMA), and quantitative insulin sensitivity check index (QUICKI) were similar in each d3/fl-GHR genotype. Group 2 glucose, insulin, and HOMA were significantly higher and QUICKI lower than in group 1. In group 3 GH-treated patients, height SDS, growth velocity SDS, fasting glucose, insulin, and HOMA significantly increased as did body mass index SDS at the end of the second year, and QUICKI decreased during the first and second years, with no differences among the d3/fl-GHR genotypes.


CONCLUSIONS
In short SGA patients, the d3/fl-GHR genotypes do not seem to influence prepubertal or pubertal insulin sensitivity indexes or their changes over 2 yr of GH therapy (66 mug/kg.d).
Audí
L
L
Servicio de Pediatría, Unidad de Endocrinología, Hospital Maternoinfantil Vall d'Hebron, Paseo Vall d'Hebron 119, Barcelona, Spain. laudi@ir.vhebron.net
Carrascosa
A
A
Esteban
C
C
Fernández-Cancio
M
M
Andaluz
P
P
Yeste
D
D
Espadero
R
R
Granada
M L
ML
Wollmann
H
H
Fryklund
L
L
D015992:Body Mass Index; D002648:Child; D005091:Exons; D005260:Female; D017353:Gene Deletion; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D019382:Human Growth Hormone / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008297:Male; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D011627:Puberty; D011986:Receptors, Somatotropin / Q000235:genetics*
D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D005947:Glucose