Sas T, Mulder P, Aanstoot H J, Houdijk M, Jansen M, Reeser M, Hokken-Koelega A
Department of Paediatrics, Division of Endocrinology, Sophia Children's Hospital/Erasmus University, Rotterdam, The Netherlands.
Clin Endocrinol (Oxf). 2001 Feb;54(2):243-51. doi: 10.1046/j.1365-2265.2001.01178.x.
To assess possible side-effects of long-term continuous growth hormone (GH) treatment on carbohydrate (CH) metabolism in children with short stature born small for gestational age.
In a prospective, randomised double-blind, dose-response multicentre trial, the effect of GH treatment on CH metabolism was evaluated, comparing two GH dosages [3 vs. 6 IU/(m(2) body surface.day)].
Seventy-eight children with short stature (height SD-score < - 1.88) born small for gestational age (birth length SD-score < - 1.88) being all prepubertal with a mean (SD) chronological age of 7.3 (2.2) years before start of treatment.
Glucose and insulin concentrations during oral glucose tolerance tests (OGTTs) and glycosylated haemoglobin (HbA(1c)) were measured before and during 6 years of GH treatment.
Before treatment, the glucose response to oral glucose after 120 min was in six of the 78 children (8%) above 7.8 mmol/l but below 11.1 mmol/l, indicating impaired glucose tolerance (IGT), whereas after 6 years of GH treatment, IGT was found in 4% of the children. None of the children developed diabetes mellitus. Mean fasting glucose levels had increased significantly by 0.5 mmol/l after 1 year of GH treatment, without a further increase thereafter. The 2-h area under the curve adjusted for fasting levels (AUCab) for glucose and the HbA(1c) levels were lower after 6 years of GH treatment compared to baseline. During GH treatment, all HbA(1c) levels were in the normal range. In contrast to the effects on glucose levels, GH treatment induced considerably higher fasting insulin levels and glucose-stimulated insulin levels. The increase in AUCab for insulin occurred particularly during the first year of treatment, whereas the fasting insulin levels showed a further increase from one to six years. As a result, the 30- and 120-min ratios of insulin to glucose were higher during GH treatment compared to the start of treatment. The children who remained prepubertal during the entire study period showed similar patterns in glucose and insulin levels compared to the children who entered puberty. None of the observed changes were different between the GH dosage groups.
Continuous GH treatment during 6 years in children with short stature born small for gestational age has no adverse effects on glucose levels, even with dosages up to 6 IU/(m(2) d). However, as has been reported in other patient groups, GH treatment induces higher fasting insulin levels and glucose-stimulated insulin levels, indicating relative insulin resistance. Since the consequences of long-term hyperinsulinism during childhood are unknown, careful follow-up of these GH-treated children born small for gestational age is required.
评估长期持续生长激素（GH）治疗对小于胎龄儿身材矮小儿童碳水化合物（CH）代谢的可能副作用。
在一项前瞻性、随机双盲、剂量反应多中心试验中，评估GH治疗对CH代谢的影响，比较两种GH剂量[3与6 IU/（m²体表面积·天）]。
78名小于胎龄儿身材矮小儿童（身高标准差评分＜ - 1.88），均为青春期前，治疗开始前平均（标准差）实足年龄为7.3（2.2）岁。
在GH治疗前及治疗6年期间，测量口服葡萄糖耐量试验（OGTT）期间的葡萄糖和胰岛素浓度以及糖化血红蛋白（HbA1c）。
治疗前，78名儿童中有6名（8%）在口服葡萄糖120分钟后的葡萄糖反应高于7.8 mmol/L但低于11.1 mmol/L，表明葡萄糖耐量受损（IGT），而在GH治疗6年后，4%的儿童出现IGT。无儿童发生糖尿病。GH治疗1年后，空腹血糖平均水平显著升高0.5 mmol/L，此后未进一步升高。与基线相比，GH治疗6年后，经空腹水平校正的葡萄糖2小时曲线下面积（AUCab）和HbA1c水平较低。在GH治疗期间，所有HbA1c水平均在正常范围内。与对葡萄糖水平的影响相反，GH治疗导致空腹胰岛素水平和葡萄糖刺激的胰岛素水平显著升高。胰岛素AUCab的增加尤其发生在治疗的第一年，而空腹胰岛素水平从1年到6年呈进一步上升趋势。因此，与治疗开始时相比，GH治疗期间胰岛素与葡萄糖的30分钟和120分钟比值更高。在整个研究期间仍处于青春期前的儿童与进入青春期的儿童在葡萄糖和胰岛素水平上表现出相似的模式。在GH剂量组之间，未观察到的变化有差异。
小于胎龄儿身材矮小儿童持续6年的GH治疗对血糖水平无不良影响，即使剂量高达6 IU/（m²·天）。然而，正如在其他患者群体中所报道的，GH治疗会导致空腹胰岛素水平和葡萄糖刺激的胰岛素水平升高，表明存在相对胰岛素抵抗。由于儿童期长期高胰岛素血症的后果尚不清楚，因此需要对这些接受GH治疗的小于胎龄儿进行仔细随访。
