Insulin treatment normalizes reduced free insulin-like growth factor-I concentrations in diabetic children
Insulin treatment normalizes reduced free insulin-like growth factor-I concentrations in diabetic children
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DOI：
10.1046/j.1365-2265.1996.7760786.x
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发表时间：
1996-09-01
影响因子：
3.2
通讯作者：
Wilson, TA
中科院分区：
文献类型：
--
作者：
Bereket, A;Lang, CH;Wilson, TA
目的：我们最近发现未经治疗的胰岛素依赖型糖尿病（IDDM）儿童血清中GH-IGF轴存在多种畸变，这些儿童在胰岛素替代治疗后恢复。然而，IGF系统中这些改变对血清中游离/生物可利用的IGF-1浓度的净结果尚未在糖尿病儿童中直接检测。在本研究中，评估糖尿病和随后的胰岛素替代对循环游离IGF-1浓度的影响。设计纵向获得空腹静脉血清样品，在未治疗的糖尿病受试者开始胰岛素治疗之前和之后的不同时间。（平均值+/- SEM）6.3 +/- 1.0岁，6例青少年，年龄12-24小时，1岁，新诊断和未经治疗的IDDM受试者，方法在开始胰岛素治疗前、治疗后12-24 h、1周、1月分别采集血清，测定胰岛素敏感性、胰岛素敏感性和胰岛素敏感性。胰岛素剂量范围从0.5至1.2 U/kg/day.MEASUREMENTS游离IGF-I浓度测定最近开发的两个网站的免疫放射分析。用酸-乙醇提取结合蛋白后，用放射免疫法测定总IGF-I。用重复测量方差分析和配对多重比较检验分析胰岛素依赖型糖尿病患者治疗前和治疗中游离和总IGF-I浓度的差异。在7名患有IDDM的受试者中，其中血清IGFBP-1和IGFBP-3浓度以及IGFBP-3蛋白酶活性也在先前的研究中被测量，通过线性回归分析来检验这些变量与循环游离IGF-1浓度之间的关系。胰岛素治疗前、治疗后1天、1周和7个月分别为1.6 +/- 0.3和2.5 +/- 0.4 μ g/l，对照青春期前儿童的游离IGF-I浓度为2.6 +/- 0.5 μ g/l。青春期受试者的游离IGF-I浓度高于青春期前受试者，但表现出相似的模式;胰岛素治疗前为2.3 +/- 1.1，1天为3.8 +/- 1.3，1周为3.7 +/- 0.6，1个月为6.5 +/- 1.5，而青春期对照组为7.7 +/- 2.0 μ g/l。在未治疗的糖尿病受试者中，总IGF-I浓度也降低，并且显示出比游离IGF-I浓度更慢的正常化模式。游离IGF-I浓度与总IGF-I呈正相关，与IGFBP-1浓度负相关，游离IGF-I与血清IGFBP-3浓度或IGFBP-3浓度之间无显著相关性。结论未治疗的IDDM期间IGF系统的改变导致循环游离IGF-I浓度的降低，其在胰岛素治疗期间逐渐恢复，游离IGF-I的增加先于总IGF-I的增加，表明前者是代谢状态的更敏感指标，游离IGF-I和IGFBP-1之间的负相关支持IGFBP-1在游离IGF-I的急性调节中起重要作用的假设。l水平。
OBJECTIVE We have recently demonstrated multiple aberrations in the GH-IGF axis in the sera of children with untreated insulin-dependent diabetes mellitus (IDDM) which were restored after insulin replacement. However, the net result of these alterations in the IGF system on the concentrations of free/biologically available IGF-I in the serum have not been examined directly in diabetic children, In the present study, the effect of diabetes and subsequent insulin replacement on the circulating free IGF-l concentrations are assessed,DESIGN Fasting venous serum samples were obtained longitudinally, before and at various times after the initiation of insulin treatment in untreated diabetic subjects.SUBJECTS Ten prepubertal, aged (mean +/- SEM) 6.3 +/- 1.0 years, and six adolescent, aged 12-24 h, 1 years, subjects with newly diagnosed and untreated IDDM, and age and pubertal status-matched control children and adolescents were recruited,METHODS The serum samples were collected before initiating insulin treatment and 12-24 h, 1 week, and 1 month thereafter in subjects with IDDM. Insulin doses ranged from 0.5 to 1.2 U/kg/day.MEASUREMENTS Free IGF-I concentration was assayed by a recently developed two-site immunoradiometric assay. Total IGF-I was measured by radioimmunoassay after acid-ethanol extraction of binding proteins, Differences in free and total IGF-I concentrations in IDDM subjects before and during insulin treatment were analysed by repeated measures analysis of variance followed by pairwise multiple comparisons test. In seven subjects with IDDM, where serum IGFBP-1 and IGFBP-3 concentrations, and IGFBP-3 protease activity had also been measured in a previous study, the relationship between these variables and circulating free IGF-1 concentrations were examined by linear regression analysis,RESULTS Free IGF-I concentrations in prepubertal subjects with IDDM were 0.9 +/- 0.2, 1.5 +/- 0.3, 1.6 +/- 0.3 and 2.5 +/- 0.4 mu g/l before, 1 day, 1 week and 7 month after insulin treatment, respectively, Free IGF-I concentrations of control prepubertal children were 2.6 +/- 0.5 mu g/l. Pubertal subjects had higher free IGF-I concentrations than prepubertal subjects but demonstrated a similar type of pattern; before insulin 2.3 +/- 1.1, 1 day 3.8 +/- 1.3, 1 week 3.7 +/- 0.6, 1 month 6.5 +/- 1.5 vs pubertal controls 7.7 +/- 2.0 mu g/l. Total IGF-I concentrations were also reduced in untreated diabetic subjects and showed a slower pattern of normalization than free IGF-I concentrations, Free IGF-I concentrations correlated positively with total IGF-I and negatively with IGFBP-1 concentrations, There was no significant correlation between free IGF-I and either serum IGFBP-3 concentrations or IGFBP-3 protease activity.CONCLUSION Alterations in the IGF system during untreated IDDM lead to a reduction in circulating free IGF-I concentrations which is restored progressively during insulin treatment, An increase in free IGF-I precedes that of total IGF-I suggesting that the former is a more sensitive indicator of the metabolic status, An inverse correlation between free IGF-I and IGFBP-1 supports the hypothesis that IGFBP-1 plays an important role in the acute modulation of free IGF-l levels.