Patel Jeetesh V, Cummings David E, Girod John P, Mascarenhas Alwin V, Hughes Elizabeth A, Gupta Manjula, Lip Gregory Y H, Reddy Sethu, Brotman Daniel J
Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine and Sandwell Medical Research Unit, Sandwell and West Birmingham Hospitals NHS Trust, West Midlands, UK.
J Negat Results Biomed. 2006 Sep 11;5:14. doi: 10.1186/1477-5751-5-14.
The mechanisms by which glucocorticoid therapy promotes obesity and insulin resistance are incompletely characterized. Modulations of the metabolically active hormones, tumour necrosis factor alpha (TNF alpha), ghrelin, leptin and adiponectin are all implicated in the development of these cardiovascular risk factors. Little is known about the effects of short-term glucocorticoid treatment on levels of these hormones.
Using a blinded, placebo-controlled approach, we randomised 25 healthy men (mean (SD) age: 24.2 (5.4) years) to 5 days of treatment with either placebo or oral dexamethasone 3 mg twice daily. Fasting plasma TNFalpha, ghrelin, leptin and adiponectin were measured before and after treatment.
Mean changes in all hormones were no different between treatment arms, despite dexamethasone-related increases in body weight, blood pressure, HDL cholesterol and insulin. Changes in calculated indices of insulin sensitivity (HOMA-S, insulin sensitivity index) were strongly related to dexamethasone treatment (p < 0.001).
Our data do not support a role for TNF alpha, ghrelin, leptin or adiponectin in the insulin resistance associated with short-term glucocorticoid treatment.
糖皮质激素治疗导致肥胖和胰岛素抵抗的机制尚未完全明确。代谢活性激素、肿瘤坏死因子α(TNFα)、胃饥饿素、瘦素和脂联素的调节均与这些心血管危险因素的发生有关。关于短期糖皮质激素治疗对这些激素水平的影响知之甚少。
采用双盲、安慰剂对照方法,我们将25名健康男性(平均(标准差)年龄:24.2(5.4)岁)随机分为两组,分别接受安慰剂或口服地塞米松3毫克,每日两次,共治疗5天。在治疗前后测量空腹血浆TNFα、胃饥饿素、瘦素和脂联素水平。
尽管地塞米松使体重、血压、高密度脂蛋白胆固醇和胰岛素升高,但各治疗组所有激素的平均变化无差异。计算得出的胰岛素敏感性指数(HOMA-S、胰岛素敏感性指数)变化与地塞米松治疗密切相关(p < 0.001)。
我们的数据不支持TNFα、胃饥饿素、瘦素或脂联素在短期糖皮质激素治疗相关的胰岛素抵抗中起作用。