Audí L, Carrascosa A, Esteban C, Fernández-Cancio M, Andaluz P, Yeste D, Espadero R, Granada M L, Wollmann H, Fryklund L
Servicio de Pediatría, Unidad de Endocrinología, Hospital Maternoinfantil Vall d'Hebron, Paseo Vall d'Hebron 119, Barcelona, Spain.
J Clin Endocrinol Metab. 2008 Jul;93(7):2709-15. doi: 10.1210/jc.2008-0150. Epub 2008 Apr 29.
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.
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.
We conducted a 2-yr prospective, controlled, randomized trial.
Thirty Spanish hospitals participated. Auxological, GH secretion, and glucose homeostasis evaluation was hospital based, whereas molecular analyses and data computation were centralized.
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).
Seventy-eight patients from group 1 were treated with GH (66 microg/kg.d) for 2 yr (group 3).
Previous and 2-yr follow-up auxological and biochemical data were recorded, d3/fl-GHR genotypes determined, and data analyzed.
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.
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).
外显子3缺失/全长（d3/fl）生长激素受体多态性（d3/fl-GHR）与小于胎龄儿（SGA）矮小患者对生长激素治疗的反应有关，尽管目前尚未达成共识。然而，其在基线或生长激素治疗期间对葡萄糖稳态的影响尚未得到研究。
我们的目的是评估d3/fl-GHR基因型是否会影响青春期前或青春期开始后或生长激素治疗期间矮小SGA儿童的胰岛素敏感性。
我们进行了一项为期2年的前瞻性、对照、随机试验。
30家西班牙医院参与了研究。身高、生长激素分泌和葡萄糖稳态评估在医院进行，而分子分析和数据计算则集中进行。
患者包括219名矮小SGA儿童[体重指数标准差评分（SDS）≤2.0]；159名处于青春期前（第1组），60名已进入青春期（第2组）。
第1组中的78名患者接受生长激素（66μg/kg·d）治疗2年（第3组）。
记录治疗前和2年随访时的身高、生化数据，确定d3/fl-GHR基因型并进行数据分析。
在第1组和第2组中，每种d3/fl-GHR基因型的空腹血糖、胰岛素、稳态模型评估（HOMA）和定量胰岛素敏感性检查指数（QUICKI）相似。第2组的血糖、胰岛素和HOMA显著高于第1组，而QUICKI低于第1组。在第3组接受生长激素治疗的患者中，第二年结束时身高SDS、生长速度SDS、空腹血糖、胰岛素和HOMA显著增加，体重指数SDS也增加，而QUICKI在第一年和第二年下降，d3/fl-GHR基因型之间无差异。
在矮小SGA患者中，d3/fl-GHR基因型似乎不影响青春期前或青春期的胰岛素敏感性指标，也不影响生长激素治疗2年（66μg/kg·d）期间这些指标的变化。
