Increased 24 h mean insulin-like growth factor binding protein-3 proteolytic activity in pubertal type 1 diabetic boys

Hyperglycaemia and increased variability of blood glucose in pubertal child ren with type 1 diabetes may be related to increased growth hormone (GH) se cretion and insulin resistance. The role of changes in insulin-like growth factor-I (IGF-I) bioavailability for the glycaemic control in these patient s has not been completely elucidated. In particular, the possible role of i ncreased IGF binding protein-3 (IGFBP-3) proteolysis reported in other insu lin resistant states awaits further characterization. The aims of this stud y were to assess if hyperglycaemia in children with type 1 diabetes was ass ociated with changes in free dissociable IGF-I (fdIGF-I) and IGF binding pr otein-3 protease activity (IGFBP-3-PA) and if increased insulin resistance during puberty was associated with changes in IGFBP-3-PA in healthy and dia betic children. In diabetic boys in the period of maximal linear growth (Ta nner stage 3, n = 5), the mean level and the variability of IGFBP-3-PA, det ermined every second hour throughout 24 h, were significantly higher both c ompared to postpubertal diabetic boys (n = 6; P = 0.003 and P = 0.001, resp ectively), and to age matched healthy boys (n = 4; P = 0.006 and P <0.001 r espectively). This activation of IGFBP-3-PA was most prominent during the d aytime. The mean 24 h blood glucose level (determined hourly) was the only parameter studied that significantly predicted the changes in mean 24 h IGF BP-3-PA in the diabetes group. The mean 24 h concentrations of fdIGF-I were decreased in the diabetic boys compared to the healthy controls but statis tical significance was only achieved in Tanner Stage 5 (P = 0.03). We specu late that the elevated levels of IGFBP-3-PA in Tanner 3 diabetic boys are r elated to deteriorated glucose homeostasis and that it may be a compensator y mechanism to attenuate the decrease in fdIGF-I in order to partly restore insulin sensitivity and glycemic control. (C) 2000 Harcourt Publishers Ltd .