LOW-DOSE CONTINUOUSLY INFUSED GROWTH-HORMONE RESULTS IN INCREASED LIPOPROTEIN(A) AND DECREASED LOW-DENSITY-LIPOPROTEIN CHOLESTEROL CONCENTRATIONS IN MIDDLE-AGED MEN

OBJECTIVE Animal studies have shown that slight increases in basal GH concentrations may result in changes in lipoprotein metabolism. Such c hanges in GH secretion have been observed in physiological and pathoph ysiological states such as fasting, uncontrolled diabetes and during o estrogen treatment. The aim of this study was to investigate the possi ble effects of increases in basal plasma GH concentrations on lipoprot ein concentrations. DESIGNS Recombinant human growth hormone (rhGH) wa s given as a continuous subcutaneous infusion in a low dose (0.02 U/kg /day) in an open study. PATIENTS Eight middle-aged (42-59 years) overw eight (body mass index: 26.1-33.8 kg/m(2)) but otherwise healthy men w ere studied over a period of 14 days. MEASUREMENTS Blood samples were obtained after an over-night fast before and after 2, 7 and 14 days of treatment. Plasma and serum were separated and used for subsequent me asurements of hormone and lipoprotein concentrations. On days 0, 7 and 14 of treatment, post-heparin plasma was also obtained for determinat ions of plasma lipoprotein lipase and hepatic lipase activities. In ad dition, a hyperinsulinaemic euglycaemic glucose clamp was performed on days 0 and 13 of the study. Fat biopsies from abdominal and gluteal f at depots were obtained for measurement of lipoprotein lipase activiti es on days 0 and 14 of the study. RESULTS Serum GH concentrations incr eased to steady level of 2-4 mU/l during treatment. Serum insulin-like growth factor-I (IGF-I) concentrations increased throughout the treat ment period to twice the pretreatment levels. Plasma insulin and blood glucose concentrations increased on day 2 of treatment. After 7 and 1 4 days of treatment blood glucose concentrations were not different fr om pretreatment levels, but plasma insulin concentrations were still e levated. Serum cholesterol and low density lipoprotein (LDL) cholester ol concentrations had decreased after 7 and 14 days of treatment. High density lipoprotein (HDL) cholesterol concentrations were not affecte d, but very low density lipoprotein (VLDL) cholesterol and triglycerid e concentrations increased transiently at day 2 of treatment. Serum ap olipoprotein (ape) A-I, apoB and apoE concentrations were not signific antly affected. Serum lipoprotein(a) concentrations had increased by d ays 7 and 14 to 147 and 142% of pretreatment concentrations, respectiv ely. Lipoprotein lipase and hepatic lipase activities in post-heparin plasma, as well as abdominal and gluteal adipose tissue lipoprotein li pase activities, were not affected. There was no significant change in glucose disposal rate estimated from the glucose clamp studies. CONCL USIONS A low dose infusion of GH results in marked changes in lipoprot ein concentrations with a transient increase in VLDL cholesterol and t hereafter in a decrease in LDL cholesterol. In addition, this low dose of GH resulted in marked increases in lipoprotein(a) concentrations. The observed effects of GH may partly involve changes in IGF-I and ins ulin secretion.