Dunger D B, Acerini C L
Department of Paediatrics, John Radcliffe Hospital, Oxford, UK.
Diabetes Metab. 1998 Apr;24(2):101-7.
Adolescents with insulin-dependent diabetes mellitus (IDDM) often experience difficulties achieving good glycaemic control, and attempts at intensifying insulin therapy may increase the risk of hypoglycaemia and weight gain. Abnormalities of the GH/IGF-I axis may contribute to these problems. Insulin-like growth factor-I (IGF-I) levels and IGF bioactivity are invariably reduced despite growth hormone (GH) hypersecretion, and these abnormalities are only partially corrected by intensified insulin therapy. The administration of recombinant human IGF-I (rhIGF-I) as an adjunct to insulin therapy can restore circulating IGF-I levels and thus suppress GH levels and improve insulin sensitivity. Randomised placebo-controlled clinical trials of daily subcutaneous rhIGF-I therapy (40-80 micrograms/kg/day) have demonstrated that significant reductions in HbA1c can be achieved without evidence of toxicity or exacerbation of diabetic complications. RhIGF-I used in conjunction with insulin may therefore provide an additional approach to the management of IDDM during adolescence, although further studies are required to determine the ideal dose regimen and confirm beneficial effects without adverse effects on microvascular complications in these subjects.
胰岛素依赖型糖尿病(IDDM)青少年患者常常在实现良好血糖控制方面遇到困难,强化胰岛素治疗的尝试可能会增加低血糖和体重增加的风险。生长激素/胰岛素样生长因子-I(GH/IGF-I)轴异常可能导致这些问题。尽管生长激素(GH)分泌过多,但胰岛素样生长因子-I(IGF-I)水平和IGF生物活性总是降低,而强化胰岛素治疗只能部分纠正这些异常。给予重组人IGF-I(rhIGF-I)作为胰岛素治疗的辅助手段,可以恢复循环中的IGF-I水平,从而抑制GH水平并提高胰岛素敏感性。每日皮下注射rhIGF-I治疗(40 - 80微克/千克/天)的随机安慰剂对照临床试验表明,在没有毒性证据或糖尿病并发症加重的情况下,糖化血红蛋白(HbA1c)可显著降低。因此,rhIGF-I与胰岛素联合使用可能为青少年IDDM管理提供另一种方法,尽管需要进一步研究以确定理想的剂量方案,并证实其有益效果且对这些受试者的微血管并发症无不良影响。