IGF-I and diabetes in adolescence.
Adolescents with insulin-dependent diabetes mellitus (IDDM) often experience difficulties achieving good glycaemic control, and attempts at intensifying insulin therapy may increase the risk of hypoglycaemia and weight gain. Abnormalities of the GH/IGF-I axis may contribute to these problems. Insulin-like growth factor-I (IGF-I) levels and IGF bioactivity are invariably reduced despite growth hormone (GH) hypersecretion, and these abnormalities are only partially corrected by intensified insulin therapy. The administration of recombinant human IGF-I (rhIGF-I) as an adjunct to insulin therapy can restore circulating IGF-I levels and thus suppress GH levels and improve insulin sensitivity. Randomised placebo-controlled clinical trials of daily subcutaneous rhIGF-I therapy (40-80 micrograms/kg/day) have demonstrated that significant reductions in HbA1c can be achieved without evidence of toxicity or exacerbation of diabetic complications. RhIGF-I used in conjunction with insulin may therefore provide an additional approach to the management of IDDM during adolescence, although further studies are required to determine the ideal dose regimen and confirm beneficial effects without adverse effects on microvascular complications in these subjects.
Dunger
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DB
Department of Paediatrics, John Radcliffe Hospital, Oxford, UK. david.dunger@paediatrics.oxford.ac.uk
Acerini
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CL
D000293:Adolescent; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000378:metabolism; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000627:therapeutic use; D011627:Puberty / Q000378:metabolism*; D011994:Recombinant Proteins / Q000627:therapeutic use
D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I