THE EFFECTS OF RECOMBINANT HUMAN INSULIN-LIKE GROWTH-FACTOR-I (IGF-I)ADMINISTRATION ON THE LEVELS OF IGF-I, IGF-II AND IGF-BINDING PROTEINS IN ADOLESCENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS

Insulin-dependent diabetes mellitus (IDDM) during puberty is associate d with a reduction in circulating concentrations of insulin-like growt h factor-I (IGF-I) and low IGF bioactivity. Altered levels of the IGF- binding proteins (IGFBPs), including low IGFBP-3 and elevated IGFBP-1, have also been described. These abnormalities have been linked to poo r growth and deteriorating blood glucose control. We have therefore ex amined the effects of recombinant human IGF-I (rhIGF-I) administration on the levels of IGF-I, IGF-II, IGFBP-1, IGFBP-3 and IGF bioactivity in a group of 9 late-pubertal adolescents with IDDM. This was a double -blind placebo controlled study with each individual admitted on two o ccasions when either rhIGF-I (40 mu g/kg) or placebo was administered by subcutaneous injection in the thigh at 1800 h. Blood samples were t hen taken for the subsequent 22 h. The half-life of administered rhIGF -I (12.1-22.2 h) was similar to that previously described in normal su bjects. There was a small increase in IGFBP-3 concentrations overnight following rhIGF-I administration when compared to placebo, whereas th e levels of IGF-II decreased. Under strict euglycaemic conditions, the relationship between insulin and IGFBP-I did not appear to be affecte d by rhIGF-I administration although the levels of IGFBP-1 tended to b e higher overnight. IGF bioactivity was low during the placebo study, and although within the normal adult range following administration of IGF-I, was still relatively low for adolescents in late puberty. Gel filtration chromatography revealed an increase in the fractions corres ponding to the 150 kDa complex throughout the duration of the study an d to a lesser extent the fractions corresponding to free IGF-I which r eached a maximum of 7% of total IGF-I levels. In conclusion, the subcu taneous administration of rhIGF-I in a dose of 40 mu g/kg to a group o f adolescents with IDDM led to a sustained increase in IGF-I levels an d a rise in IGF bioactivity despite a fall in IGF-II and a trend towar ds higher IGFBP-1 concentrations.