Different thresholds of metabolic GH effects in prepubertal children

• Context: In addition to growth hormone (GH) effects to promote linear growth in children, GH also has substantial effects on insulin sensitivity, lipolysis, lipids, and body composition. A dissociation between anabolic and lipolytic GH effects has been suggested. Objective: The objective of the present study was to further investigate dissociated GH effects by calculating the GH doses to attain half of a given metabolic effect, the effective dose 50% (ED50%). Hypothesis: The hypothesis was that there are dose-dependent thresholds in different variables reflecting metabolism. Design: A randomized, prospective, multicentre trial was performed for a 2 years period, with two treatment regimens in short prepubertal GHD and ISS children a) individualized GH dose with six different dose groups ranging 17-100 g/kg/day (n=87) and b) fixed GH dose of 43 g/kg/day (n=41). Results: Contrary to changes in fat mass, leptin, lipids and skinfold measurements, there was evidence for different thresholds in metabolic variables for a given GH dose when performing ANOVA, p<0.001. was calculated as the difference between 2 years and start of GH treatment. Besides height (SDS), growth related variables like weight SDS and BMI (kg/m ); measures of body composition such as fat-free mass (FFM) (kg), FFM index (FFMI) (kg/m ), waist (cm), hip (cm); as well as biochemical markers like IGF-1 (SDS), IGFBP-3 (SDS); insulin (mU/L) showed dose-dependency with different ED50% levels. Conclusions: Differences of the ED50% on metabolic variables were seen in-between different GH dose spans. Thus we propose that there are different thresholds in GH effects on variables reflecting different metabolic aspects, suggesting muscle tissue being more sensitive than linear growth, GH induced insulin resistance, the rise in IGF-1 and the increase in hip circumference as a measure of 3-dimensional body growth.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

Growth hormone

insulin

insulin resistance

thresholds

metabolism

body composition

DEXA

lipolysis

anabolism

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