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 associated with a reduction in circulating concentrations of insulin-like growth 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 poor growth and deteriorating blood glucose control. We have therefore examined 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 occasions when either rhIGF-I (40 micrograms/kg) or placebo was administered by subcutaneous injection in the thigh at 1800 h. Blood samples were then 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 subjects. There was a small increase in IGFBP-3 concentrations overnight following rhIGF-I administration when compared to placebo, whereas the levels of IGF-II decreased. Under strict euglycaemic conditions, the relationship between insulin and IGFBP-I did not appear to be affected by rhIGF-I administration although the levels of IGFBP-1 tended to be 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Cheetham
T D
TD
Department of Paediatrics, John Radcliffe Hospital, Headington, Oxford, UK.
Taylor
A
A
Holly
J M
JM
Clayton
K
K
Cwyfan-Hughes
S
S
Dunger
D B
DB
D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology; D013002:Somatomedins / Q000032:analysis
D002352:Carrier Proteins; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II