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The effects of recombinant insulin-like growth factor I administration on growth hormone levels and insulin requirements in adolescents with Type 1 (insulin-dependent) diabetes mellitus
Authors:T. D. Cheetham  J. Jones  A. M. Taylor  J. Holly  D. R. Matthews  D. B. Dunger
Affiliation:(1) Department of Paediatrics, John Radcliffe Hospital, Oxford, UK;(2) Department of Growth and Development, Institute of Child Health, University of London, London, UK;(3) Department of Chemical Endocrinology, St Bartholomew's Hospital, London, UK;(4) Diabetes Research Laboratories, Radcliffe Infirmary, Oxford, UK
Abstract:Summary Type 1 (insulin-dependent) diabetes mellitus in adolescence is associated with reduced levels of insulin-like growth factor I, elevated growth hormone concentrations and insulin resistance. In order to determine whether restoring insulin-like growth factor I levels to normal might lead to a reduction in growth hormone levels and insulin requirements, we undertook a double-blind placebo controlled study of a single s. c. dose of recombinant insulin-like growth factor I (40 mgrg/kg body weight) in nine late pubertal subjects with Type 1 diabetes. After administration of placebo or insulin-like growth factor I at 18.00 hours, a variable rate insulin infusion was used to maintain euglycaemia overnight. Plasma insulin-like growth factor I, growth hormone, free insulin, and intermediate metabolite concentrations were monitored throughout the study. Recombinant insulin-like growth factor I led to a rise in plasma concentrations which reached a peak at 5.5 h (413.1±28.2 ng/ml, mean±SEM). Mean growth hormone levels between 20.00 and 08.00 hours were significantly reduced after recombinant insulin-like growth factor I (19.4±4.0 compared with 33.6±5.8 mU/l; p=0.01), as were the insulin requirements for euglycaemia (0.25±0.02 compared with 0.31±0.04 mU · kg–1 · min–1; p=0.03). Plasma free insulin levels were lower after recombinant insulin-like growth factor I administration (31.9±2.7 compared with 67.9±16.0 mU/l; p=0.001) but no significant differences in ketone or lactate levels were detected. Recombinant insulin-like growth factor I in a s. c. dose of 40 mgrg/kg body weight leads to a significant reduction in overnight growth hormone levels and insulin requirements in adolescents with Type 1 diabetes.
Keywords:Type 1 (insulin-dependent) diabetes mellitus  insulin requirements  insulin-like growth factor I  growth hormone  adolescence
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