Context: The exon 3-deleted/full-length growth hormone receptor polymorphism (exon 3-deleted/full-length-GHR) has been associated with responsiveness to GH therapy in short SGA patients, although consensus is lacking. However, its influence on glucose homeostasis, at baseline or under GH therapy, has not been investigated.

Objective: To evaluate whether the exon 3-deleted/full-length-GHR genotypes influence insulin sensitivity in short SGA children before or after puberty onset or during GH therapy.

Design: Two-year prospective controlled randomized trial.

Setting: Thirty Spanish hospitals participated. Auxologic, GH secretion and glucose homeostasis evaluation was hospital-based whereas molecular analyses and data computation were centralized.

Patients: Two hundred and nineteen short SGA children (BMI-SDS2.0): 159 were prepubertal (Group 1) and 60 had entered puberty (Group 2).

Intervention: Seventy-eight patients from Group 1 were treated with GH (66µg/kg/day) for 2 years (Group 3).

Main outcome measures: Previous and two-year follow-up auxologic and biochemical data were recorded, exon 3-deleted/full-length-GHR genotypes determined and data analyzed.

Results: In groups 1 and 2, fasting glucose, insulin, HOMA and QUICKI indexes were similar in each exon 3-deleted/full-length-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 BMI-SDS at the end of the 2^nd year and QUICKI decreased during the first and second years, with no differences among the exon 3-deleted/full-length-GHR genotypes.

Conclusion: In short SGA patients, the exon 3-deleted/full-length-GHR genotypes do not seem to influence prepubertal or pubertal insulin sensitivity indexes or their changes over 2 years of GH therapy (66 µg/kg/day).