title: The effects of repeated daily recombinant human insulin-like growth factor I administration in adolescents with type 1 diabetes.
abstract: Reduced insulin-like growth factor bioactivity has been linked to poor metabolic control and growth hormone hypersecretion in adolescents with Type 1 diabetes. The safety and efficacy of recombinant human insulin-like growth factor I administered subcutaneously in a dose of 40 micrograms kg-1 for 28 days was studied in a group of 6 adolescent male subjects with Type 1 diabetes (aged 13.6-19.4 years, puberty stage 3-5). After a 4-week run-in period (week -4 day 0) recombinant human insulin-like growth factor I was administered for 4 weeks (day 0 to week +4) before a run-out of a further 4 weeks duration (week +4 to +8). HbA1c levels were measured throughout the study and overnight profiles were undertaken to study levels of insulin-like growth factor 1, insulin-like growth factor binding protein-3, and growth hormone concentrations (week -1, day 0, and week +4). The injections were well tolerated and hypoglycaemia was not problematic at any stage of the study. Recombinant insulin-like growth factor I administration appeared to lead to a sustained increase in insulin-like growth factor I levels (week -1; 198 +/- 16 ng ml-1, week +4; 422 +/- 18 ng ml-1, mean +/- SEM; p = 0.03). Insulin-like growth factor binding protein-3 concentrations (n = 6) increased in 5 subjects (week -1; 4.5 +/- 0.3 micrograms ml-1, week +4; 5.1 +/- 0.4 micrograms ml-1) and mean overnight growth hormone decreased (week -1; 14.0 +/- 3.1 mUI-1, week +4; 7.6 +/- 1.7 mUI-1) during the period of study but these differences were not statistically significant. HbA1c levels fell significantly at the time of rhIGF-I administration (day 0; 10.4 +/- 1.9% vs week +4; 9.4 +/- 1.9%; p = 0.03) despite a reduction in subcutaneous isophane insulin dose from 0.50 +/- 0.02 U kg-1 to 0.41 +/- 0.02 U kg-1 (p = 0.03). There was no significant change in biochemical and haematological indices, glomerular filtration rate or urinary albumin excretion. The restoration of IGF-I levels in adolescents with Type 1 diabetes may have a beneficial impact on glycaemic control.
authors.affiliation: Department of Paediatrics, John Radcliffe Hospital, Oxford, UK.
authors.forename: T D
authors.initials: TD
authors.lastname: Cheetham
authors.forename: J M
authors.initials: JM
authors.lastname: Holly
authors.forename: K
authors.initials: K
authors.lastname: Clayton
authors.forename: S
authors.initials: S
authors.lastname: Cwyfan-Hughes
authors.forename: D B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D004334:Drug Administration Schedule; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood / Q000627:therapeutic use*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011627:Puberty; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D006442:Glycated Hemoglobin; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D011994:Recombinant Proteins