Growth and insulin-like growth factors (IGFs) in children with insulin-dependent diabetes mellitus at the onset of disease: Evidence for normal growth, age dependency of the IGF system alterations, and presence of a small (approximately 18-kilodalton) IGF-binding protein-3 fragment in serum

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 diag nosis, most of previous studies are affected by the small number of patient s investigated. We studied 60 IDDM children at the onset of disease, compar ing their statue with target height, normal growth standards, and height of 102 sex- and age-matched controls. Furthermore, we assessed serum IGF-I, I GF-II, and IGF-binding protein-3 (IGFBP-3) levels and IGFBP-3 circulating f orms. IDDM ckildren were subdivided into 2 groups according to an age above (n = 26) or below (n = 34) 6 yr. The values of endocrine variables of diab etics older than 6 yr were compared with those of 34 age-matched controls. Although the height of diabetics was higher than growth reference values (m ean height +/- SD, 0.64 +/- 1.4 z-score) and their target height (mean targ et height +/- SD, 0.1 +/- 0.84 z-score; P < 0.005), no significant differen ce 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. Over all, 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 patien ts younger than 6 yr showed normal values of IGF-I, IGF-II, and IGFBP-3, th ese peptides were significantly reduced in older subjects compared with eit her younger IDDM children or controls (P < 0.01). IGFBP-3 immunoblot analys is 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 (si milar to 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 betw een the endocrine variables and stature at diagnosis. In conclusion, our re sults indicate that IDDM ckildren at the onset of disease are not taller th an 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.