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

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.

Efficacy and safety of growth hormone treatment in Japanese children with small-for-gestational-age short stature in accordance with Japanese guidelines

“…Our findings are consistent with the reports by Horikawa et al. and Tanaka et al who have also reported similar results for the effects of rhGH treatment in patients with SGA short stature in Japan ( 15 , 16 ). Considering the present and previous results, it is assumed that rhGH treatment does not impose a particular risk for the development of type 2 diabetes, although rhGH treatment caused a slight increase in the glucose tolerance-related parameters based on insulin resistance.…”

“…Horikawa et al . reported that they did not find any adverse effects on glucose metabolism in a clinical trial in Japanese children with SGA short stature ( 15 ). In this study, we also found that HbA1c, fasting blood glucose levels, IRI levels, and the sigma IRI of the OGTT were higher during treatment than before treatment.…”

Early Growth Hormone Intervention Improves Glucose Metabolism in Adult Rats Born Small for Gestational Age

“…Some studies revealed that insulin sensitivity and β-cell function in SGA individuals improved after GH treatment and no adverse metabolic events developed in rodents and humans [19,30]. Other studies showed that SGA children exhibited higher fasting insulin levels and elevated HOMA-IR over time with GH treatment, while after discontinuation of GH, serum insulin levels returned to normal age-related levels [27,31]. In our study, SGA rats ▶Fig.…”

“…GH performs a wide range of roles and exhibits a significant effect on glucose and lipid metabolism. Many studies conducted in SGA children showed that long-term continuous GH treatment does not adversely affected glucose metabolism parameters, but also might have a potentially beneficial effect on several parameters in lipid metabolism [26][27][28]. In parallel, our previous study showed that GH treatment normalized serum triglycerides in SGA rats in adulthood [29].…”

Metabolic and immunological assessment of small-for-gestational-age children during one-year treatment with growth hormone: the clinical impact of apolipoproteins

“…Serum cholesterol level is the main readout for the lipid profile evaluation to determine the risk of cardiovascular events in the SGA population, and GH treatment of SGA children was reported to improve the patients' cholesterol profiles in several studies [6,11,19]. Apolipoproteins, the protein constituents of lipoprotein particles, were recently reported to be superior to cholesterol for estimating the risk of cardiovascular events [20][21][22].…”