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目的探讨重组人生长激素(rhGH)替代治疗对生长激素缺乏症(GHD)儿童糖和胰岛素代谢的影响以及 GH 与糖代谢平衡之间的关系。方法对44例(男28例,女16例)4.5～16.5(10.4±2.6)岁 GHD 患儿在接受 rhGH 治疗前及治疗后每3个月检测体重指数、胰岛素样生长因子-1(IGF-1)、行口服葡萄糖耐量试验,计算稳态模型胰岛素抵抗指数。结果 (1)空腹血糖和 IGF-1在治疗3个月时即显著提高,一直持续较高水平,每个随访时间点与治疗前比较,差异均有统计学意义(F=6.81,7.31,P 均<0.01);稳态模型胰岛素抵抗指数和空腹胰岛素分别在治疗3和9个月时提高(P<0.01和 P<0.05),1年后下降,治疗1年半时与治疗前比较,差异已无统计学意义(均 P>0.05)。(2)相关分析发现,稳态模型胰岛素抵抗指数与体重指数、IGF-1和治疗持续时间显著相关(r=0.251,0.437,0.281,P 均<0.001)。二次方程曲线回归分析发现,稳态模型胰岛素抵抗指数与治疗持续时间呈近似抛物线量变关系。(3)发现2例暂时性高血糖,分别在停用 rhGH 治疗后1个月和5d 血糖恢复正常,再注射 rh GH 后,行口服葡萄糖耐量试验正常。结论 GHD 儿童接受 rhGH 治疗(尤第1年内)可增加胰岛素抵抗,极少数引起短暂糖代谢紊乱。循环 IGF-1可能参与控制胰岛素的敏感性,在 GH 与胰岛素平衡间起重要作用。有必要对所有接受 rhGH 治疗者定期监测糖代谢指标和 IGF-1水平。
Objective To investigate the effects of rhGH replacement therapy on glucose and insulin metabolism in children with growth hormone deficiency (GHD) and the relationship between GH and glucose metabolism. Methods Forty-four (14 males and 28 females and 16 females) 4.5 to 16.5 (10.4 ± 2.6) years old children with GHD were tested for body mass index, insulin-like growth factor-1 (IGF- 1), oral glucose tolerance test, calculate the steady-state model of insulin resistance index. Results (1) Fasting plasma glucose and IGF-1 increased significantly at 3 months of treatment, and remained high continuously. The difference was statistically significant at each follow-up time point before treatment (F = 6.81, 7.31, P (All P <0.01). Insulin resistance index and fasting insulin in steady-state model increased at 3 and 9 months (P <0.01 and P <0.05), decreased at 1 year and at 1 year and a half after treatment, respectively No statistical significance (all P> 0.05). (2) The correlation analysis showed that the steady-state model of insulin resistance index was significantly associated with body mass index, IGF-1 and duration of treatment (r = 0.251,0.437,0.281, P <0.001). Quadratic curve regression analysis found that steady-state model of insulin resistance index and the duration of treatment showed a similar parabolic relationship. (3) Two cases of transient hyperglycemia were found. The blood glucose returned to normal one and five days after the rhGH treatment was stopped. After the rhGH injection, the oral glucose tolerance test was normal. Conclusion GHD children receiving rhGH treatment (especially within the first year) can increase insulin resistance, a very small number caused by transient glucose metabolism disorders. Circulating IGF-1 may be involved in the control of insulin sensitivity, GH and insulin balance play an important role. It is necessary to regularly monitor glycometabolism and IGF-1 levels in all rhGH-treated patients.