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

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 mug/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 mug/kg body weight leads to a significant reduction in overnight growth hormone levels and insulin requirements in adolescents with Type 1 diabetes.