重组人生长激素治疗神经性厌食症的随机、安慰剂对照研究。
Effects of recombinant human growth hormone in anorexia nervosa: a randomized, placebo-controlled study.
机构信息
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
出版信息
J Clin Endocrinol Metab. 2010 Nov;95(11):4889-97. doi: 10.1210/jc.2010-0493. Epub 2010 Jul 28.
CONTEXT
Anorexia nervosa (AN), a state of chronic nutritional deprivation, is characterized by GH resistance with elevated GH levels and decreased levels of IGF-I. The effects of supraphysiological recombinant human GH (rhGH) on GH resistance in AN are not currently known.
OBJECTIVE
The aim was to investigate whether supraphysiological rhGH increases IGF-I levels in AN.
DESIGN AND SETTING
We conducted a randomized, placebo-controlled study in a Clinical Research Center.
PATIENTS
We studied 21 women with AN, 10 (mean age, 28 ± 2.1 yr) treated with rhGH and 11 (mean age, 29.2 ± 2.6 yr) treated with placebo.
INTERVENTIONS
rhGH (mean maximum daily dose, 1.4 ± 0.12 mg/d) or placebo was administered to patients for 12 wk.
MAIN OUTCOME MEASURES
IGF-I, N-terminal propeptide of type 1 procollagen, type I collagen C-telopeptide, glucose, and insulin levels were measured at wk 0, 1, 2, 3, 4, 8, and 12; C-terminal propeptide of type 1 procollagen, leptin, and free fatty acid levels were measured at wk 0 and 12. Body composition, including total fat and lean mass, was measured by dual-energy x-ray absorptiometry at wk 0 and 12.
RESULTS
IGF-I levels did not differ between the groups at baseline or after treatment (median after 12 wk-rhGH, 124 ng/ml, interquartile range, 94.5, 170.3; vs. placebo, 85.5 ng/ml, interquartile range, 62, 139; P = 0.3). Similarly, changes in glucose, insulin, free fatty acids, and bone markers did not differ between the groups. Total fat mass and percentage fat mass (rhGH, -2.5 ± 0.6%, vs. placebo, 2.2 ± 1.1%; P = 0.004) decreased significantly in the rhGH group compared to placebo despite comparable weight.
CONCLUSIONS
Supraphysiological rhGH administration decreases fat mass in AN without increasing IGF-I levels, supporting the role of GH as a mediator of lipolysis independent of IGF-I.
背景
神经性厌食症(AN)是一种慢性营养缺乏状态,其特征是 GH 抵抗,表现为 GH 水平升高和 IGF-I 水平降低。目前尚不清楚超生理剂量的重组人生长激素(rhGH)对 AN 中 GH 抵抗的影响。
目的
本研究旨在探讨超生理剂量 rhGH 是否能增加 AN 患者的 IGF-I 水平。
设计和设置
我们在临床研究中心进行了一项随机、安慰剂对照研究。
患者
我们研究了 21 名 AN 女性患者,其中 10 名(平均年龄 28 ± 2.1 岁)接受 rhGH 治疗,11 名(平均年龄 29.2 ± 2.6 岁)接受安慰剂治疗。
干预措施
rhGH(平均最大日剂量 1.4 ± 0.12mg/d)或安慰剂治疗患者 12 周。
主要观察指标
IGF-I、I 型前胶原 N 端前肽、I 型胶原 C 端肽、葡萄糖和胰岛素水平在第 0、1、2、3、4、8 和 12 周时测定;I 型前胶原 C 端肽、瘦素和游离脂肪酸水平在第 0 和 12 周时测定。在第 0 和 12 周时通过双能 X 射线吸收法测量身体成分,包括总脂肪和瘦体重。
结果
两组患者基线或治疗后 IGF-I 水平无差异(治疗 12 周后 rhGH 中位数为 124ng/ml,四分位间距为 94.5、170.3;安慰剂中位数为 85.5ng/ml,四分位间距为 62、139;P=0.3)。同样,两组间葡萄糖、胰岛素、游离脂肪酸和骨标志物的变化也无差异。rhGH 组总脂肪量和脂肪百分比(rhGH,-2.5±0.6%,安慰剂,2.2±1.1%;P=0.004)较安慰剂组显著下降,尽管体重相当。
结论
超生理剂量 rhGH 给药可减少 AN 患者的脂肪量,而不增加 IGF-I 水平,支持 GH 作为 IGF-I 独立的脂解介质的作用。