Mauras Nelly, George Donald, Evans Jonathan, Milov David, Abrams Steven, Rini Annie, Welch Susan, Haymond Morey W
Nemours Children's Clinic, Jacksonville, FL, USA.
Metabolism. 2002 Jan;51(1):127-35. doi: 10.1053/meta.2002.28972.
The present studies were designed to determine whether recombinant human growth hormone (rhGH) can counteract some of the catabolic effects of glucocorticosteroid therapy in children chronically treated with glucocorticosteroids. Whether rhGH can safely improve short-term linear growth was also investigated. The effect of rhGH on disease activity was also assessed. Ten children (6 boys, 4 girls) with inflammatory bowel disease (IBD) on oral prednisone for at least 4 months prior to these studies were recruited (mean +/- SE, 11.9 +/- 0.9 years). Leucine and glucose isotope studies, body composition, substrate oxidation and energy expenditure rates, and growth factors were measured at baseline (D1) and at 4 months after treatment with rhGH (0.05 mg/ kg. d subcutaneously [SC]) while continuing oral prednisone. Dual-emission x-ray absorptiometry (DEXA) and calcium kinetic analysis ((42)Ca/(46)Ca) were performed also. rhGH was continued for 6 months to assess linear growth in all 10 subjects, 7 of whom continued rhGH for 12 months. Body composition changed favorably with increased fat free mass (+3 kg, P =.001) and decreased percent fat mass (-3.5%, P =.001) after 4 months of treatment. Rates of whole body protein turnover, oxidation, and synthesis remained invariant, with no changes in substrate oxidation or resting energy expenditure rates. Linear growth velocity increased from 3.5 +/- 0.4 cm/yr when the patients were treated with prednisone only, to 7.7 +/- 0.9 after 6 months of combined prednisone/rhGH (P =.001). The growth velocity was sustained in the 7 patients treated with rhGH for 12 months. Plasma insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) concentrations also increased significantly while on rhGH treatment. No changes in calcium absorption were observed but there was a significant increase in kinetic rates of bone calcium accretion (P =.045) as well as in bone-specific alkaline phosphatase concentrations, a measure of bone formation (P =.03). Fasting and 2-hour postprandial glucose concentrations, fasting insulin levels, and HbA(1C) were invariant during combined rhGH/prednisone treatment. The Crohn's disease activity score was unchanged with rhGH therapy. In summary, rhGH treatment of corticosteroid-dependent patients with IBD was associated with positive changes in body composition, bone metabolism, and linear growth, without deterioration of carbohydrate tolerance or intermediate metabolism of substrates. We conclude that treatment with rhGH has beneficial effects in prednisone-dependent growing children. Larger studies will be needed to assess the long-term safety and efficacy of this approach.
本研究旨在确定重组人生长激素（rhGH）是否能抵消糖皮质激素疗法对长期接受糖皮质激素治疗的儿童的某些分解代谢作用。还研究了rhGH是否能安全地改善短期线性生长。同时评估了rhGH对疾病活动的影响。招募了10名炎症性肠病（IBD）患儿（6名男孩，4名女孩），这些患儿在本研究前至少4个月一直在口服泼尼松（平均±标准误，11.9±0.9岁）。在基线时（D1）以及rhGH（0.05mg/kg·d皮下注射[SC]）治疗4个月后，在继续口服泼尼松的同时，进行亮氨酸和葡萄糖同位素研究、身体成分分析、底物氧化和能量消耗率测定以及生长因子检测。还进行了双能X线吸收法（DEXA）和钙动力学分析（（42）Ca/（46）Ca）。10名受试者均接受rhGH治疗6个月以评估线性生长，其中7名受试者继续接受rhGH治疗12个月。治疗4个月后，身体成分得到有利变化，无脂肪量增加（+3kg，P = 0.001），脂肪量百分比降低（-3.5%，P = 0.001）。全身蛋白质周转、氧化和合成率保持不变，底物氧化或静息能量消耗率无变化。仅接受泼尼松治疗时患者的线性生长速度为3.5±0.4cm/年，泼尼松/rhGH联合治疗6个月后增至7.7±0.9（P = 0.001）。接受rhGH治疗12个月的7名患者的生长速度得以维持。rhGH治疗期间血浆胰岛素样生长因子I（IGF-I）和胰岛素样生长因子结合蛋白-3（IGFBP-3）浓度也显著升高。未观察到钙吸收变化，但骨钙积聚的动力学率显著增加（P = 0.045），同时骨特异性碱性磷酸酶浓度（骨形成的一项指标）也显著增加（P = 0.03）。rhGH/泼尼松联合治疗期间空腹和餐后2小时血糖浓度、空腹胰岛素水平及糖化血红蛋白（HbA1C）均无变化。rhGH治疗后克罗恩病活动评分未改变。总之，rhGH治疗依赖皮质类固醇的IBD患者与身体成分、骨代谢和线性生长的积极变化相关，且未导致碳水化合物耐受性或底物中间代谢恶化。我们得出结论，rhGH治疗对依赖泼尼松的正在生长的儿童有有益作用。需要进行更大规模的研究来评估该方法的长期安全性和有效性。
