Lewandowski Krzysztof C, Murray Robert D, Drzewoski J, O'Callaghan Chris J, Czupryniak L, Hillhouse Edward W, Shalet Stephen M, Randeva Harpal S
Molecular Medicine Research Group, Biomedical Research Institute, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK.
Mol Genet Metab. 2003 Nov;80(3):330-7. doi: 10.1016/j.ymgme.2003.08.020.
Growth hormone (GH) deficiency is associated with increased cardiovascular morbidity and mortality. GH treatment improves the profile of many cardiovascular risk markers in individuals with GH deficiency (GHD). The aim of the present was to assess whether GH replacement may decrease plasma total homocysteine, an independent cardiovascular risk factor, thus potentially contributing to benefits of GH replacement in adult subjects with GHD. Twenty-five patients (17 female, 8 male), mean age 39-years, with GHD were studied. GH status had been determined by an insulin tolerance test and/or arginine stimulation test. After an overnight fast, plasma insulin, IGF-1, total homocysteine (Hcy), free thyroxine (FT4), creatinine, vitamin B12, and folate were measured at baseline (V1), 3 months (V2) and then at 6 months (V3) on GH treatment. The data were analysed by hierarchical statistical models, univariate and multivariate correlation. GH treatment resulted in an increase in IGF-1 (p<0.001, p<0.001), and insulin (p=0.068, p<0.001), at each visit, respectively. Hcy levels increased from V1 to V2 (7.7+/-0.53 to 9.15+/-0.45 micromol/L; p=0.051), but this was followed by a decline at V3 (to 8.8+/-0.59), so that the overall change of Hcy levels from V1 to V3, once individuals had achieved 'adequate' GH replacement, was no longer significantly different (p=0.090). When separated by gender, at 6 months (V3) there was a small, but significant increase in Hcy in men (p=0.028), but not in women (p=0.58). There was no significant change in B12, folate, free T4 or creatinine levels. Univariate analysis revealed that only B12 and folate showed significant negative relationships with Hcy (B12: parameter= -0.013, p<0.001; folate: parameter=-1.31, p<0.001), but not between Hcy and IGF-1 (p=0.18). In a multiple variable model, both B12 and folate remained significantly negatively associated with plasma total homocysteine (p=0.018; p<0.001, respectively). In this observational study normalisation of IGF-1 levels in adult subjects with growth hormone deficiency was not associated with a fall in total homocysteine. Before firm conclusions can be drawn about the contribution of changes in plasma homocysteine concentrations to cardiovascular prognosis in adult GHD patients receiving GH replacement, further controlled studies are required.
生长激素（GH）缺乏与心血管疾病发病率和死亡率增加相关。生长激素治疗可改善生长激素缺乏症（GHD）患者多种心血管风险标志物的状况。本研究的目的是评估生长激素替代治疗是否可降低血浆总同型半胱氨酸水平（一种独立的心血管危险因素），从而可能有助于生长激素替代治疗对成年GHD患者的益处。对25例患者（17例女性，8例男性）进行了研究，平均年龄39岁，均患有GHD。生长激素状态通过胰岛素耐量试验和/或精氨酸刺激试验确定。在过夜禁食后，于生长激素治疗的基线期（V1）、3个月（V2）和6个月（V3）测量血浆胰岛素、胰岛素样生长因子-1（IGF-1）、总同型半胱氨酸（Hcy）、游离甲状腺素（FT4）、肌酐、维生素B12和叶酸。数据采用分层统计模型、单变量和多变量相关性分析。生长激素治疗导致每次随访时IGF-1水平升高（p<0.001，p<0.001），胰岛素水平升高（p=0.068，p<0.001）。Hcy水平从V1到V2升高（7.7±0.53至9.15±0.45μmol/L；p=0.051），但随后在V3时下降（至8.8±0.59），因此，一旦个体实现“充分”的生长激素替代，从V1到V3的Hcy水平总体变化不再有显著差异（p=0.090）。按性别分开分析，6个月时（V3）男性的Hcy有小幅但显著升高（p=0.028），而女性则无（p=0.58）。维生素B12、叶酸、游离T4或肌酐水平无显著变化。单变量分析显示，只有维生素B12和叶酸与Hcy呈显著负相关（维生素B12：参数=-0.013，p<0.001；叶酸：参数=-1.31，p<0.001），但Hcy与IGF-1之间无相关性（p=0.18）。在多变量模型中，维生素B12和叶酸均与血浆总同型半胱氨酸显著负相关（分别为p=0.018；p<0.001）。在这项观察性研究中，成年生长激素缺乏患者IGF-1水平正常化与总同型半胱氨酸水平下降无关。在就血浆同型半胱氨酸浓度变化对接受生长激素替代治疗的成年GHD患者心血管预后的影响得出确切结论之前，还需要进一步的对照研究。
