INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS IN PREPUBERTAL CHILDREN WITH INSULIN-DEPENDENT DIABETES-MELLITUS

To study the possible role of insulin-like growth factor binding prote ins (IGFBPs) in the discrepancy between normal or only slightly retard ed growth and substantially reduced concentrations if insulin-like gro wth factor I (IGF-I) in prepubertal children with insulin-dependent di abetes mellitus (IDDM), we measured the plasma concentrations of IGF-I , IGFBP-1, IGFBP-2 and IGFBP-3 and free insulin in 24 prepubertal diab etic subjects and 12 control children. In addition, the growth hormone response to exercise was evaluated. The diabetic children had signifi cantly decreased peripheral IGF-I levels (8.2 +/- 1.1 (SEM) VS 16.7 2.5 nmol/l; p < 0.001), whereas the concentrations of free insulin wer e increased (217 +/- 14 vs 103 + 21 pmol/l; p < 0.001). The concentrat ions of IGFBP-1 and IGFBP-3 were of the same magnitude in both groups. The diabetic children had significantly increased levels of IGFBP-2 ( 465 + 13 vs 416 + 14 mu g/l; p = 0.029), which were inversely related to the circulating IGF-I levels (r = -0.35; p = 0.034). The diabetic a nd control children had comparable growth hormone responses to exercis e. Diabetic children with poor glucose control had even lower IGF-I le vels than those with moderate metabolic control (6.0 + 0.8 vs 10.3 + 1 .7 nmol/l; p = 0.037). No differences could be observed in the plasma concentrations of various IGFBPs between these two groups of diabetic subjects. The absence in prepubertal diabetic children of increased IG FBP-1 levels observed in adolescent and adult patients with IDDM may c ontribute to their maintained linear growth, despite definitely decrea sed IGF-I concentrations. The role of increased IGFBP-2 levels in prep ubertal children with IDDM remains open, but the inverse relationship between IGF-I levels and IGFBP-2 concentrations suggests that IGF-I ma y be involved in the regulation of IGFBP-2.