title: The influence of a long-term growth hormone treatment on lipid and glucose metabolism: a randomized trial in short Japanese children born small for gestational age.
abstract: BACKGROUND
  Long-term growth hormone (GH) treatments in short children born small for gestational age (SGA) restore lipid metabolism, but also increase insulin resistance. The aim of this study was to evaluate the influence of long-term GH therapy on lipid and glucose metabolism as well as its dose dependency in short Japanese children born SGA.
  
  
  METHODS
  Eighty Japanese children with a short stature who were born SGA participated in this study; 65 were treated with fixed GH doses of 0.033 (low) or 0.067 (high) mg/kg/day for 260 weeks; 15 were untreated controls in the first year and were randomized to one of the two treatment groups at week 52. Serum cholesterol, glucose and insulin levels were regularly measured. An oral glucose tolerance test (OGTT) was conducted annually.
  
  
  RESULTS
  The mean age at the start of GH therapy was approximately 5.3 years. Serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the high dose group significantly decreased over time during GH therapy. In both dose groups for TC, and in the high dose group for LDL-C, the higher the baseline values, the greater the decrease after 260 weeks. The rate of the decrease observed after 260 weeks in patients with high LDL-C levels was greater in the high dose group. Based on the results of OGTT, no patient was classified as being diabetic; however, annual increases were observed in post-OGTT insulin levels. After 260 weeks, the homeostasis model assessment as an index of insulin resistance (HOMA-IR) increased, suggesting that insulin resistance developed over time with the GH treatment, while 36.6 % of the subjects entered puberty.
  
  
  CONCLUSIONS
  Long-term continuous GH treatment for children born SGA may have a potentially beneficial effect on several parameters in lipid metabolism and does not adversely affect glucose metabolism.
  
  
  BACKGROUND
  GHLIQUID-1516, GHLIQUID-1517, Japan Pharmaceutical Information Center Clinical trial registration: JapicCTI-050132. Registered 13 September 2005. Retrospectively registered. JapicCTI-050137. Registered 13 September 2005. Retrospectively registered. ClinicalTrials.gov trial registration: NCT00184717. Registered 13 September 2005. Retrospectively registered.
authors: Division of Endocrinology and Metabolism, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535 Japan.
authors: Reiko
authors: R
authors: Horikawa
authors: Tanaka Growth Clinic, 2-36-7 Yoga, Setagaya-ku, Tokyo, 158-0097 Japan.
authors: Toshiaki
authors: T
authors: Tanaka
authors: CMR Development Division, Novo Nordisk Pharma Ltd., 2-1-1 Marunouchi, Chiyoda-ku, Tokyo, 100-0005 Japan.
authors: Hiromi
authors: H
authors: Nishinaga
authors: CMR Development Division, Novo Nordisk Pharma Ltd., 2-1-1 Marunouchi, Chiyoda-ku, Tokyo, 100-0005 Japan.
authors: Yoshihisa
authors: Y
authors: Ogawa
authors: Department of Medical Subspecialties, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535 Japan.
authors: Susumu
authors: S
authors: Yokoya
keywords: GH therapy; Glucose metabolism; Growth hormone; Insulin resistance; Japanese; Lipid metabolism; Norditropin®; Short stature; Small for gestational age