Bach M A, Chin E, Bondy C A
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
J Clin Endocrinol Metab. 1994 Oct;79(4):1040-5. doi: 10.1210/jcem.79.4.7525624.
Insulin-dependent diabetes can be associated with low insulin-like growth factor-I (IGF-I) levels despite normal or even high GH secretion. The basis of the diabetic abnormalities in GH-IGF dynamics that contribute to insulin resistance and impaired fuel metabolism are not well understood. To further investigate these matters, this study evaluated baseline IGF system parameters and responses to recombinant human IGF-I in four diabetic adolescents and six pubertal stage-matched controls. Spontaneous overnight and arginine-stimulated GH secretion, insulin, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), and IGFBP-3 levels were measured before, during, and after daily 10-h sc infusions of saline or IGF-I (20 micrograms/kg.h). Baseline overnight GH secretion and IGFBP-1 and -3 levels were not significantly different in the two groups, but IGF-I levels were significantly lower and IGF-II levels were higher in diabetic subjects. IGF-I infusion produced a 3-fold increase in serum IGF-I levels and a reciprocal profound reduction in IGF-II levels in both groups. IGFBP-1 levels increased dramatically in diabetics and modestly in normal subjects in response to IGF-I infusion, but IGFBP-3 levels were not significantly altered. Spontaneous overnight and arginine-stimulated GH secretion were suppressed by about 50% in both groups after IGF-I infusion. Insulin requirements were substantially reduced in diabetics receiving IGF-I, and insulin secretion was suppressed in normal subjects, with no evidence of a change in insulin half-life. Blood glucose remained stable in both groups throughout saline and IGF-I infusions, and no hypoglycemia or other adverse effect occurred during IGF-I infusions. Further studies are necessary to determine whether the addition of IGF-I to insulin replacement therapy may stably reduce the insulin requirement, maintain normal GH levels, and perhaps achieve better metabolic and anabolic balance in the treatment of insulin-dependent diabetes.
胰岛素依赖型糖尿病可能与胰岛素样生长因子-I（IGF-I）水平低下有关，尽管生长激素（GH）分泌正常甚至升高。导致胰岛素抵抗和燃料代谢受损的GH-IGF动态变化中的糖尿病异常基础尚未完全明确。为了进一步研究这些问题，本研究评估了4名糖尿病青少年和6名青春期阶段匹配的对照组的基线IGF系统参数以及对重组人IGF-I的反应。在每天10小时皮下输注生理盐水或IGF-I（20微克/千克·小时）之前、期间和之后，测量了自发夜间和精氨酸刺激后的GH分泌、胰岛素、IGF-I、IGF-II、IGF结合蛋白-1（IGFBP-1）和IGFBP-3水平。两组的基线夜间GH分泌以及IGFBP-1和-3水平无显著差异，但糖尿病患者的IGF-I水平显著降低，IGF-II水平较高。IGF-I输注使两组血清IGF-I水平增加了3倍，IGF-II水平相应大幅降低。糖尿病患者的IGFBP-1水平在IGF-I输注后显著升高，正常受试者则略有升高，但IGFBP-3水平无显著变化。IGF-I输注后，两组的自发夜间和精氨酸刺激后的GH分泌均被抑制约50%。接受IGF-I的糖尿病患者胰岛素需求大幅降低，正常受试者胰岛素分泌受到抑制，且无胰岛素半衰期改变的证据。在整个生理盐水和IGF-I输注过程中，两组血糖均保持稳定，IGF-I输注期间未发生低血糖或其他不良反应。有必要进行进一步研究，以确定在胰岛素替代治疗中添加IGF-I是否能稳定降低胰岛素需求、维持正常GH水平，并可能在胰岛素依赖型糖尿病治疗中实现更好的代谢和合成代谢平衡。
