Abstract
BackgroundLong-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.MethodsEighty 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.ResultsThe 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.ConclusionsLong-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.Trial registrationGHLIQUID-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.
Highlights
Long-term growth hormone (GH) treatments in short children born small for gestational age (SGA) restore lipid metabolism, and increase insulin resistance
We examined the relationship between baseline status and changes of lipid metabolism-associated parameters after long-term (260 weeks) GH therapy, in addition to effects on other metabolic parameters including glycated hemoglobin A1c (HbA1c), blood glucose and insulin levels before and after an oral glucose tolerance test (OGTT), homeostasis model assessment as an index of insulin resistance (HOMA-IR), and insulinogenic index
This study investigated the effect of long term continuous GH treatment in children born SGA on lipid and glucose metabolism
Summary
Long-term growth hormone (GH) treatments in short children born small for gestational age (SGA) restore lipid metabolism, and 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. Rapid catch-up in the weight of these children has been suggested to increase the risk of various medical conditions [6, 7]. The mechanisms underlying these risks have been examined, with increases in insulin resistance and/or intra-abdominal fat being implicated in this phenomenon [8]. Increases in insulin resistance may cause impairments in the growth hormone (GH)-insulin-like growth factor (IGF)-binding protein axis or be a consequence of these impairments [9]
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