Subdivision of Endocrinology, Department of Pediatrics, Erasmus University Medical Center, Rotterdam, Netherlands.
Subdivision of Endocrinology, Department of Pediatrics, Erasmus University Medical Center, Rotterdam, Netherlands.
Lancet Diabetes Endocrinol. 2017 Feb;5(2):106-116. doi: 10.1016/S2213-8587(16)30422-3. Epub 2016 Dec 21.
Growth hormone treatment reduces fat mass and insulin sensitivity and increases lean body mass. Data are only available for short-term longitudinal changes after cessation of growth hormone treatment in young adults born small for gestational age. We aimed to assess long-term changes over a 5-year period following cessation of growth hormone treatment.
We did a longitudinal study of young adults born small for gestational age and previously treated with growth hormone. Individuals were followed up for 5 years after attainment of adult height, when growth hormone treatment was discontinued: assessments were done at cessation of growth hormone treatment and at 6 months, 2 years, and 5 years thereafter. Data 5 years after cessation of growth hormone were compared with untreated age-matched controls. We used dual-energy x-ray absorptiometry to assess body composition, and did frequently sampled intravenous glucose tolerance tests to assess insulin sensitivity, acute insulin response, and the disposition index (a measure of β-cell function). This study is registered with ISRCTN, numbers ISRCTN96883876 and ISRCTN65230311.
Between April, 2004, and April, 2016, we followed up 199 young adults born small for gestational age and previously treated with growth hormone, during the 5 years after cessation of growth hormone treatment. Data at 5 years for these individuals were compared with those for 51 untreated adults born small for gestational age with short stature, 92 untreated adults born small for gestational age with spontaneous catch-up growth, and 142 adults born appropriate for gestational age and unexposed to growth hormone treatment. In young adults born small for gestational age and previously treated with growth hormone, 5 years after cessation of growth hormone treatment, there were increases in fat mass (estimated marginal mean 10·73 kg [95% CI 9·95-11·50] at cessation of treatment vs 16·12 kg [14·77-17·46] at 5 years; p<0·0001), trunk fat (5·34 kg [4·94-5·73] vs 7·86 kg [7·12-8·60]; p<0·0001), and limb fat (4·87 kg [4·49-5·25] vs 7·41 kg [6·78-8·05]; p<0·0001); furthermore, lean body mass had decreased (42·41 kg [95% CI 41·09-43·73] at cessation of treatment vs 41·42 kg [40·17-42·66] at 5 years; p=0·0013). Insulin sensitivity increased within 6 months of cessation and was sustained 5 years after treatment cessation (estimated marginal mean 4·14 mU/L [95% CI 3·79-4·53] at cessation of treatment vs 6·15 mU/L [5·21-7·24] at 5 years; p<0·0001), and acute insulin response was diminished at 6 months, which persisted at 5 year follow-up (597·63 mU/L [539·62-661·86] vs 393·69 mU/L [337·56-459·15]; p<0·0001). The disposition index was increased 6 months after treatment but values at 5 years were similar to those at cessation of treatment (2483·94 [95% CI 2233·43-2762·54] at cessation of treatment vs 2367·83 [2033·43-2757·22] at 5 years; p=0·49). 5 years after cessation of growth hormone treatment, adults born small for gestational age and previously treated with growth hormone had fat mass, insulin sensitivity, and disposition index similar to those of untreated adults born small for gestational age with short stature, but lean body mass (adjusted for sex and height) was lower (46·47 kg [44·95-48·00] in those born small for gestational age with short stature vs 44·32 kg [43·35-45·30] in those born small for gestational age and treated with growth hormone; p=0·007). In adults previously treated with growth hormone born small for gestational age, at 5 years after cessation of growth hormone treatment, compared with adults born small for gestational age with spontaneous catch-up growth and adults born appropriate for gestational age, lean body mass was lower and results from frequently sampled intravenous glucose tolerance tests were similar.
Significant changes in body composition and insulin sensitivity were recorded 5 years after cessation of growth hormone treatment in adults born small for gestational age, reflecting a loss of pharmacological effects of growth hormone. 5 years after cessation of treatment, fat mass, insulin sensitivity, and β-cell function of previously treated adults were similar to untreated adults born small for gestational age with short stature, indicating that long-term growth hormone treatment in children born small for gestational age has no unfavourable effects on metabolic health in early adulthood.
Novo Nordisk Farma BV (Netherlands).
生长激素治疗可减少脂肪量和胰岛素敏感性，增加瘦体重。目前仅可获得在胎龄较小的成年人接受生长激素治疗停止后的短期纵向变化数据。我们旨在评估生长激素治疗停止后 5 年内的长期变化。
我们对以前接受过生长激素治疗的胎龄较小的成年人进行了一项纵向研究。在达到成人身高后，停止生长激素治疗 5 年时对患者进行了随访：在生长激素治疗停止时和 6 个月、2 年和 5 年后进行评估。停止生长激素治疗 5 年后的数据与未经治疗的年龄匹配的对照组进行了比较。我们使用双能 X 射线吸收法评估身体成分，并进行了频繁采样的静脉葡萄糖耐量试验，以评估胰岛素敏感性、急性胰岛素反应和处置指数（β细胞功能的衡量标准）。这项研究在 ISRCTN 注册，注册号为 ISRCTN84153423 和 ISRCTN65230311。
在 2004 年 4 月至 2016 年 4 月期间，我们对 199 名胎龄较小且以前接受过生长激素治疗的成年人进行了随访，在生长激素治疗停止后的 5 年内。将这些患者的 5 年数据与未经治疗的 51 名胎龄较小且身材矮小、92 名胎龄较小且有自然追赶生长的未经治疗患者以及 142 名胎龄合适且未暴露于生长激素治疗的成年人进行了比较。在胎龄较小且以前接受过生长激素治疗的成年人中，停止生长激素治疗 5 年后，脂肪量增加（停止治疗时的估计边际均值为 10.73kg[95%CI 9.95-11.50]，5 年时为 16.12kg[14.77-17.46]；p<0.0001）、躯干脂肪（5.34kg[4.94-5.73]vs 7.86kg[7.12-8.60]；p<0.0001）和肢体脂肪（4.87kg[4.49-5.25]vs 7.41kg[6.78-8.05]；p<0.0001）；此外，瘦体重减少（停止治疗时的估计边际均值为 42.41kg[95%CI 41.09-43.73]，5 年时为 41.42kg[40.17-42.66]；p=0.0013）。停止治疗后 6 个月内胰岛素敏感性增加，治疗停止后 5 年仍持续（停止治疗时的估计边际均值为 4.14mU/L[95%CI 3.79-4.53]，5 年时为 6.15mU/L[5.21-7.24]；p<0.0001），急性胰岛素反应在 6 个月时降低，在 5 年随访时仍持续（597.63mU/L[539.62-661.86]vs 393.69mU/L[337.56-459.15]；p<0.0001）。治疗停止后 6 个月时处置指数增加，但 5 年时的值与停止治疗时相似（停止治疗时为 2483.94[95%CI 2233.43-2762.54]，5 年时为 2367.83[2033.43-2757.22]；p=0.49）。生长激素治疗停止 5 年后，胎龄较小且以前接受过生长激素治疗的成年人的脂肪量、胰岛素敏感性和处置指数与未经治疗的胎龄较小且身材矮小的成年人相似，但瘦体重（按性别和身高调整）较低（胎龄较小且身材矮小的成年人为 46.47kg[44.95-48.00]，胎龄较小且接受过生长激素治疗的成年人为 44.32kg[43.35-45.30]；p=0.007）。在生长激素治疗停止后 5 年的胎龄较小且以前接受过生长激素治疗的成年人中，与有自然追赶生长的胎龄较小的成年人和胎龄合适的成年人相比，瘦体重较低，且频繁采样的静脉葡萄糖耐量试验结果相似。
在胎龄较小的成年人停止生长激素治疗 5 年后，记录到了身体成分和胰岛素敏感性的显著变化，反映了生长激素的药理作用丧失。停止治疗 5 年后，以前接受过治疗的成年人的脂肪量、胰岛素敏感性和β细胞功能与胎龄较小且身材矮小的未经治疗的成年人相似，表明在胎龄较小的儿童中进行长期生长激素治疗对成年早期的代谢健康没有不利影响。
诺和诺德 Farma BV（荷兰）。
