Knobler H, Schattner A
Department of Medicine, Addenbrooke's Hospital, University of Cambridge School of Clinical Medicine, Cambridge CB2 2QQ, UK.
QJM. 2005 Jan;98(1):1-6. doi: 10.1093/qjmed/hci001.
Patients with chronic hepatitis C virus (HCV) infection have a significantly increased prevalence of type 2 DM compared to controls or HBV-infected patients, independent of the presence of cirrhosis. Moreover, antecedent HCV infection markedly increases the risk of developing DM in susceptible subjects. Even non-diabetic HCV patients have insulin resistance and specific defects in the insulin-signalling pathway. Activation of the tumour necrosis factor (TNF)-alpha system has a pivotal role in the inflammatory process of chronic hepatitis C, and TNF-alpha levels correlate with the degree of inflammation. TNF-alpha is known to cause insulin resistance, with similar defects in the insulin signalling pathway to those described in HCV infection. A model of mice transgenic for the HCV core protein demonstrated insulin resistance, glucose intolerance, and elevated intrahepatic TNF-alpha mRNA; all of which were ameliorated by anti-TNF-alpha antibodies. In addition, diabetic HCV patients have significantly higher levels of soluble TNF-alpha receptors, compared to non-diabetic HCV patients and controls. TNF-alpha may be the link between HCV infection and diabetes, suggesting an additional mechanism of diabetes with important implications for prognosis and therapy.
与对照组或乙型肝炎病毒（HBV）感染患者相比，慢性丙型肝炎病毒（HCV）感染患者2型糖尿病的患病率显著增加，且与肝硬化的存在无关。此外，既往HCV感染显著增加了易感人群患糖尿病的风险。即使是非糖尿病的HCV患者也存在胰岛素抵抗以及胰岛素信号通路的特定缺陷。肿瘤坏死因子（TNF）-α系统的激活在慢性丙型肝炎的炎症过程中起关键作用，且TNF-α水平与炎症程度相关。已知TNF-α会导致胰岛素抵抗，其胰岛素信号通路缺陷与HCV感染中描述的类似。一种HCV核心蛋白转基因小鼠模型表现出胰岛素抵抗、葡萄糖不耐受以及肝内TNF-α mRNA升高；而抗TNF-α抗体可改善所有这些情况。此外，与非糖尿病HCV患者及对照组相比，糖尿病HCV患者的可溶性TNF-α受体水平显著更高。TNF-α可能是HCV感染与糖尿病之间的联系，提示了一种对预后和治疗具有重要意义的糖尿病额外机制。
