D I S C U S S I O N A N D V A L O R I Z A T I O N A D D E N D U M Small for gestational age children Besides the evidence of the origin of the metabolic syndrome in SGA children, it is also remarkable that their growth in length and height often stay behind the norm. One of the factors mentioned with respect to the stunted growth SGA children is reduced sensitivity for the insulin-‐like growth factor 1 (IGF-‐1)8. IGF-‐1 is mainly secreted by the liver as a result of stimulation by growth hormone. IGF-‐1 expres-‐ sion is required for achieving maximal growth. Short SGA children show plasma IGF-‐1 levels that are in the lower normal range9. For that reason these children are treated with recombinant human growth hormone (rhGH) nowadays. In general they respond very good on this treatment and correct their height towards their genetically defined percentile. At the same time it is known from that treatment of growth hormone deficient (GHD) children with rhGH results in a change of the me-‐ tabolism10. This change is assumed to be an effect of IGF-‐I what is a primary regula-‐ tor of systemic anabolism and muscle growth11. Growth hormone deficiency is as-‐ sociated with increased body fat and a lower lean body mass. These changes in body composition are associated with metabolic derangements including insulin resistance. They normalize with growth hormone replacement therapy12. In this thesis we showed that treatment with rhGH has also a positive metabolic effect on body composition of SGA children. The treatment with rhGH causes a shift in body composition of FM towards FFM. After treatment with rhGH, SGA children show an increase in height but also in weight. The detected increase in weight is based on an increase in FFM and not in FM. This means, as mentioned before, that the body composition in SGA children improves after receiving rhGH treatment. In SGA children rhGH treatment prevents overweight and thereby the metabolic syn-‐ drome. To evaluate adequate and inadequate responders to rhGH therapy, with respect to height, changes in body composition can be measured. The change in body compo-‐ sition is an actual tool in predicting the individual response on rhGH treatment. By using this method rhGH therapy can be given only to adequate responders and it is possible to prevent aimless administration. In obese children there exists a decrease in growth hormone (GH) secretion what is fully reversible when body weight is normalized13. A decrease in spontaneous GH release in obesity has been confirmed in several comparative studies on the 24-‐ hour secretion of GH in normal weight14 and obese children13, 15. In obese children, GH secretion may be as low as in poorly growing children with classical GHD16. Investigation of the pattern of factors potentially influencing GH secretion con-‐ firmed a significant and independent impact of fat mass. Relative adiposity acts as a negative determinant of the frequency and amplitude of GH secretory bursts. They are associated with an increased GH clearance leading to a lower GH half-‐life time, 109
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