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Lipolytic and anabolic effects of GH are dissociated during individualized GH treatment

Paper i proceeding
Författare Ralph Decker
Kerstin Albertsson-Wikland
Jovanna Dahlgren
Berit Kriström
Publicerad i European Society for Paediatric Endocrinology
Volym 70
Nummer/häfte Supplement Issue 1
ISBN 978-3-8055-8620-7
Publiceringsår 2008
Publicerad vid Institutionen för kliniska vetenskaper
Språk en
Ämnesord metabolic GH effects
Ämneskategorier Klinisk farmakologi

Sammanfattning

Context: There is a broad variation in longitudinal growth response during GH treatment among prepubertal children. Yet, growth is but one of the several effects of GH. Our working hypothesis was a dissociation of anabolic and lipolytic effects of GH. Objective: To investigate whether diverse metabolic functions respond analogical to growth. Design: A randomized, prospective, multicentre trial was performed, for a 2 years period, with two treatment regimens providing the same mean GH dose a) individualized GH dose, six different dose groups ranging 17-100 µg/kg/day (n=87) and b) standard GH dose: 43 µg/kg/day (n=41). Patients: 128 prepubertal short children, 75% of them diagnosed as GH deficient and 25% as idiopathic short stature. Main Outcome Measures: Changes in metabolic variables (delta 2 years - start). Results: Changes in IGF-1 correlated to height gain (r=0.54, p<0.0001). Stepwise regression showed that 71% of the variation in IGF-1 was explained by height gain (49%), chnages in insulin (9%), free fat mass (FFM) (5%), and biceps skinfold (4%), as well as GH dose (4%). Changes in IGF-1 solely accounted for all changes in FFM (31%). In contrast to total fat mass, changes in FFM were significantly higher after 2 years of GH doses above 40 µg/kg/day (p<0.001 Mann-Whitney test). In principle component analysis it can be demonstrated that the anabolic variables IGF-1, IGFBP-3, FFM, and insulin target in the same direction as height gain. All variables in this vector bundle show high reciprocal partial regressions. The anabolic component is dose-dependent. Variables derived from adipose tissue (total fat mass, leptin, skin fold measurements, triglycerides) and lipid metabolism (cholesterol, HDL, LDL, triglycerides, lipoprotein(a), apolipoprotein A-II) form up a lipolytic bundle. This is unrelated to the anabolic component and dose-independent. Conclusions: This study suggests that lipolytic and anabolic effects of GH are dissociated. The threshold of GH's lipolytic effects is much lower than its anabolic and growth effects.

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