国产r-hGH治疗儿童生长激素缺乏症的效果及其对病儿血糖、胃肠激素和维生素D代谢的影响

THE THERAPEUTIC EFFECT OF CHINA-MADE RECOMBINANT HUMAN GROWTH HORMONE ON CHILDREN WITH GROWTH HORMONE DEFICIENCY AND ITS INFLUENCE ON THE SERUM LEVELS OF GLUCOSE,GASTRIN AND VITAMIN D

目的 评价国产基因重组人生长激素（r-hGH）治疗儿童生长激素缺乏症（GHD）的效果和安全性，观察该疗法对病儿血糖、胃泌素、胃动素和维生素D代谢的影响。方法 68例GHD病儿接受国产r-hGH治疗12个月，剂量0．1U／（kg·d），治疗前及治疗后3、6、12个月分别测定身高、体质量、骨龄。对其中15例在治疗前及治疗后3个月进行口服葡萄糖耐量试验（OGTT）和胰岛素（INS）释放试验（IRT）。对其中20例在治疗前及治疗后3个月观察血清胃泌素、胃动素、25（OH）D3、1，25-（OH）2D3水平，并与非GH缺乏性矮身材（NGHDSS）病儿和正常儿童相对照。结果 r-hGH治疗后3、6、12个月时GHD儿童身高增长速度与治疗前相比明显加快。治疗前15例病儿糖耐量均正常．治疗后3个月OGTT空腹血糖（PG）无明显增加，但PG30min、PG1h、PG2h、血糖曲线下面积（AUCglu）均明显增加（t=2．49～3．30，P〈0．05）；尽管葡萄糖耐量曲线上移，但所有病儿均未出现糖耐量损伤（IGT）或糖尿病（DM）。IRT空腹INS、INS 30 min、INS1h、INS2h、胰岛素曲线下面积（AUCins）均显著增加，稳态模型的胰岛素抵抗指数（Homa IR）明显上升（t=2．18～3．12，P〈0．05）。GHD病儿治疗前血清胃泌素水平低于正常对照组（t=2．27．P〈0．01）；治疗3个月后血清胃泌素水平较治疗前略增加，但差别无显著意义（P〉0．05）。GHD病儿治疗前后血清胃动素水平与正常对照组无显著性差别（P〉0．05）。GHD病儿治疗前血清25（OH）D3水平低于对照组和NGHDSS组（t=4．91、2．39，P〈0．05），治疗3个月后较治疗前增加并高于对照组（t=20．60、17．82，P〈0．05）。治疗前血清1，25（OH）2D3水平，GHD组、NGHDSS组与正常对照组无差别（P〉0．05）；治疗3个月后较治疗前增加并高于对照组（t=10．09、11．36，P％0．05）。结论 国产r-hGH治疗儿童GHD安全，有效。r-hGH替代治疗3个月后胰岛素敏感性下降，糖耐量降低，对应用r-hGH替代治疗的GHD病儿应监测血糖和INS水平。GH可能影响胃泌素的合成和分泌。r-hGH促进维生素D的代谢。

Objective To evaluate the therapeutic effect of China-made recombinant human growth hormone （r-hGH） on children with growth hormone deficiency （GHD） and to observe the influence of the replacement therapy on the serum levels of glucose, gastrin and vitamin D. Methods Sixty-eight children with GItD were included in this study. They were treated with China made r hGH replacement therapy for 12 months, with dosage of 0. 1 U/（kg·d）. The body height, body weight and bone age were separately examined 3, 6, and 12 months before and after the treatment. Oral glucose tolerance test （OGTT） and insulin releasing test （IRT） were also performed 3 months before and after the therapy in 15 children with GHD. Serum levels of gastrin, 25 （OH）D3, 1,25 （OH）2D3, were measured 3 months before and after the therapy in 20 GHD children too. The results obtained were compared with those of children with non-GHD short stature （NGHDSS, n=20） and the normal children （n=20）. Results The growths of GHD children after 3, 6 and 12 months of therapy were obviously increased. Before the treatment the OGTT were normal in 15 patients. After 3 months of r-hGH therapy, fasting plasma glucose remained unchanged, but PG 30 rain, PG 1 h, PG 2 h and glucose areas under the curve （AUCglu） increased significantly （t=2.49-3.30,P〈0. 05）. Although an upward displacement of the glucose curve after r-hGH treatment was observed, impaired glucose tolerance and diabetes mellitus were not found in all patients. Fasting insulin. INS 30 min, INS 1 h, INS 2 h, insulin areas under the curve and Homa IR increased significantly （t= 2.18-3. 12,P〈0.05）. Before the treatment, the serum levels of gastrin were lower in GHD children than those in NGHDSS children and controls （t=2.27,P〈0.01） and not increased significantly after treatment （P〉0. 05）. Similarly, the serum levels of 25 （OH）D3 were significantly lower in GIlD children than those in NGHDSS and controls before the treatment （t= 4.91,2.39; P〈 0. 05）, but significantly increased in children with GHD after 3 months of r-hGH therapy and were higher than those in controls （t=20.60,17.82; P〈0.05）. The serum levels of 1,25-（OH）2D3 before treatment were similar among the children with GHD, NGHDSS and controls, and were significantly increased in children with GHD after 3 months of r-hGH therapy and were higher than those in control group （t=10.09.11.36;P〈0.05）. Conclusion The use of China-made r-hGH to treat the children with GHD is effective and safe. h is necessary to monitor the serum levels of PG and INS during r-hGH replacement therapy, r-hGH may influence the synthesis and secretion of gastrin, and improve the metabolism of vitamin D.