Serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in children with insulin-dependent diabetes mellitus

Pubertal development has recently been evaluated from the standpoint of changes in insulinlike growth factor (IGF)-I and IGF-binding protein-3 (IGFBP-3) levels in healthy children, We studied puberty related changes in serum IGF-I and IGFBP-3 levels in 24 patients (11 prepubertal) with insulin dependent diabetes mellitus (IDDM) and 26 healthy subjects (14 prepubertal), Serum IGF-I and IGFBP-3 levels were assayed using immunoradiometric assays and radioimmunoassays, respectively, Serum IGF-I and IGFBP-3 levels in diabetics did not increase during puberty, as opposed to those in healthy children, Serum IGF-I and IGFBP-3 levels of diabetic patients were found to be lower than those of control subjects during puberty (p<0.0001 and p<0.05, respectively), Proteolysis is believed to be a general mechanism to increase IGF bioavailability in the presence of IGFBPs, Increased IGFBP-3 protease activity has been shown in sera of children with IDDM as well as a decrease in this activity in response to insulin therapy, Our data displaying low IGFBP-3 levels in diabetic children may be due to increased proteolysis, which also causes a shift in IGF-I to its lower molecular weight forms. Higher rate of clearance of the latter may be the reason for the low IGF-I levels we observed in children with IDDM. The moderate correlation between insulin dose and IGFBP-3 levels (r=0.5, p<0.01) may suggest insulin to be a contributing factor in the regulation of IGFBP-3 levels, We conclude that regulation of IGF-I and IGFBP-3 concentrations is disturbed in children with IDDM, in particular during adolescence.