Prodam Flavia, Savastio Silvia, Genoni Giulia, Babu Deepak, Giordano Mara, Ricotti Roberta, Aimaretti Gianluca, Bona Gianni, Bellone Simonetta
Division of Pediatrics, Department of Health Sciences, University of "Piemonte Orientale Amedeo Avogadro", Novara, Italy ; Endocrinology, Department of Clinical and Experimental Medicine, University of Piemonte Orientale, Novara, Italy ; I.C.O.S. (Interdisciplinary Center for Obesity Study), Novara, Italy.
Division of Pediatrics, Department of Health Sciences, University of "Piemonte Orientale Amedeo Avogadro", Novara, Italy.
PLoS One. 2014 Jan 30;9(1):e87157. doi: 10.1371/journal.pone.0087157. eCollection 2014.
Growth hormone deficiency (GHD) is associated with insulin resistance and diabetes, in particular after treatment in children and adults with pre-existing metabolic risk factors. Our aims were. i) to evaluate the effect on glucose metabolism of rhGH treatment and withdrawal in not confirmed GHD adolescents at the achievement of adult height; ii) to investigate the impact of GH receptor gene genomic deletion of exon 3 (d3GHR).
We performed a longitudinal study (1 year) in a tertiary care center.
23 GHD adolescent were followed in the last year of rhGH treatment (T0), 6 (T6) and 12 (T12) months after rhGH withdrawal with fasting and post-OGTT evaluations. 40 healthy adolescents were used as controls. HOMA-IR, HOMA%β, insulinogenic (INS) and disposition (DI) indexes were calculated. GHR genotypes were determined by multiplex PCR.
In the group as a whole, fasting insulin (p<0.05), HOMA-IR (p<0.05), insulin and glucose levels during OGTT (p<0.01) progressively decreased from T0 to T12 becoming similar to controls. During rhGH, a compensatory insulin secretion with a stable DI was recorded, and, then, HOMAβ and INS decreased at T6 and T12 (p<0.05). By evaluating the GHR genotype, nDel GHD showed a decrease from T0 to T12 in HOMA-IR, HOMAβ, INS (p<0.05) and DI. Del GHD showed a gradual increase in DI (p<0.05) and INS with a stable HOMA-IR and higher HDL-cholesterol (p<0.01).
In not confirmed GHD adolescents the fasting deterioration in glucose homeostasis during rhGH is efficaciously coupled with a compensatory insulin secretion and activity at OGTT. The presence of at least one d3GHR allele is associated with lower glucose levels and higher HOMA-β and DI after rhGH withdrawal. Screening for the d3GHR in the pediatric age may help physicians to follow and phenotype GHD patients also by a metabolic point of view.
生长激素缺乏症（GHD）与胰岛素抵抗及糖尿病相关，尤其是在对已有代谢危险因素的儿童和成人进行治疗后。我们的目的是：i）评估重组人生长激素（rhGH）治疗及停药对未确诊GHD青少年成年身高达成时葡萄糖代谢的影响；ii）研究生长激素受体基因第3外显子基因组缺失（d3GHR）的影响。
我们在一家三级医疗中心进行了一项为期1年的纵向研究。
23名GHD青少年在rhGH治疗的最后一年（T0）、停药后6个月（T6）和12个月（T12）接受随访，进行空腹及口服葡萄糖耐量试验（OGTT）后评估。40名健康青少年作为对照。计算稳态模型评估胰岛素抵抗（HOMA-IR）、稳态模型评估β细胞功能（HOMA%β）、胰岛素生成指数（INS）和处置指数（DI）。通过多重聚合酶链反应确定生长激素受体（GHR）基因型。
在整个研究组中，空腹胰岛素水平（p<0.05）、HOMA-IR（p<0.05）、OGTT期间的胰岛素和血糖水平（p<0.01）从T0到T12逐渐下降，与对照组相似。在rhGH治疗期间，记录到代偿性胰岛素分泌且处置指数稳定，随后，HOMAβ和INS在T6和T12时下降（p<0.05）。通过评估GHR基因型，nDel GHD组从T0到T12时HOMA-IR、HOMAβ、INS（p<0.05）和DI下降。Del GHD组处置指数（p<0.05）和INS逐渐升高，HOMA-IR稳定，高密度脂蛋白胆固醇水平较高（p<0.01）。
在未确诊GHD的青少年中，rhGH治疗期间空腹血糖稳态的恶化与OGTT时的代偿性胰岛素分泌及活性有效相关。至少存在一个d3GHR等位基因与rhGH停药后较低的血糖水平、较高的HOMA-β和处置指数相关。在儿童期筛查d3GHR可能有助于医生从代谢角度对GHD患者进行随访及分型。
