Cianfarani S, Bonfanti R, Bitti M L, Germani D, Boemi S, Chiumello G, Boscherini B
Department of Pediatrics, Tor Vergata University, Rome, Italy.
J Clin Endocrinol Metab. 2000 Nov;85(11):4162-7. doi: 10.1210/jcem.85.11.6996.
Data on growth of children with insulin-dependent diabetes mellitus (IDDM) before the onset of disease are conflicting, and although the insulin-like growth factor (IGF) system has almost invariably been found altered at diagnosis, most of previous studies are affected by the small number of patients investigated. We studied 60 IDDM children at the onset of disease, comparing their stature with target height, normal growth standards, and height of 102 sex- and age-matched controls. Furthermore, we assessed serum IGF-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) levels and IGFBP-3 circulating forms. IDDM children were subdivided into 2 groups according to an age above (n = 26) or below (n = 34) 6 yr. The values of endocrine variables of diabetics older than 6 yr were compared with those of 34 age-matched controls. Although the height of diabetics was higher than growth reference values (mean height +/- SD, 0.64+/-1.4 z-score) and their target height (mean target height +/- SD, 0.1+/-0.84 z-score; P < 0.005), no significant difference in height was found between IDDM children and controls (mean height +/- SD, 0.64+/-0.95 z-score) even analyzing the 2 age groups separately. Overall, IDDM children showed reduced levels of IGF-I (mean +/- SD, -0.65+/-1.9 z-score) and normal levels of IGF-II (mean +/- SD, -0.05+/-1.2 z-score) and IGFBP-3 (mean +/- SD, -0.06+/-1.2 z-score). However, whereas patients younger than 6 yr showed normal values of IGF-I, IGF-II, and IGFBP-3, these peptides were significantly reduced in older subjects compared with either younger IDDM children or controls (P < 0.01). IGFBP-3 immunoblot analysis revealed the presence of an approximately 18-kDa fragment of IGFBP-3 in addition to the major approximately 29-kDa fragment and the intact form (approximately 42-39 kDa) in 46 of 60 IDDM patients, whereas the approximately 18-kDa band was absent in all 34 control sera. No relationship was found between the endocrine variables and stature at diagnosis. In conclusion, our results indicate that IDDM children at the onset of disease are not taller than healthy peers and have increased IGFBP-3 proteolytic activity. Finally, although the IGF system is normal in younger IDDM children, older patients have reduced IGF levels.
胰岛素依赖型糖尿病（IDDM）患儿发病前生长数据存在矛盾，尽管几乎在诊断时均发现胰岛素样生长因子（IGF）系统发生改变，但既往大多数研究受限于所调查患者数量较少。我们研究了60例IDDM患儿发病时的情况，将他们的身高与靶身高、正常生长标准以及102例年龄和性别匹配的对照者的身高进行比较。此外，我们评估了血清IGF-I、IGF-II和IGF结合蛋白-3（IGFBP-3）水平以及IGFBP-3的循环形式。IDDM患儿根据年龄分为两组，6岁以上（n = 26）和6岁以下（n = 34）。将6岁以上糖尿病患者的内分泌变量值与34例年龄匹配的对照者进行比较。尽管糖尿病患儿的身高高于生长参考值（平均身高+/-标准差，0.64 +/- 1.4 z评分）及其靶身高（平均靶身高+/-标准差，0.1 +/- 0.84 z评分；P < 0.005），但即使分别分析这两个年龄组，IDDM患儿与对照者之间的身高也无显著差异（平均身高+/-标准差，0.64 +/- 0.95 z评分）。总体而言，IDDM患儿的IGF-I水平降低（平均+/-标准差，-0.65 +/- 1.9 z评分），IGF-II（平均+/-标准差，-0.05 +/- 1.2 z评分）和IGFBP-3（平均+/-标准差，-0.06 +/- 1.2 z评分）水平正常。然而，6岁以下患者的IGF-I、IGF-II和IGFBP-3值正常，与6岁以下IDDM患儿或对照者相比，6岁以上患者这些肽水平显著降低（P < 0.01）。IGFBP-3免疫印迹分析显示，60例IDDM患者中有46例除主要的约29 kDa片段和完整形式（约42 - 39 kDa）外，还存在约18 kDa的IGFBP-3片段，而所有34例对照血清中均未出现约18 kDa条带。诊断时内分泌变量与身高之间未发现相关性。总之，我们的结果表明，发病时的IDDM患儿并不比健康同龄人高，且具有增强的IGFBP-3蛋白水解活性。最后，尽管年幼的IDDM患儿IGF系统正常，但年长患者的IGF水平降低。
