QJM vol. 98 no. 1 © Association of Physicians 2005; all rights reserved.
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TNF-
, chronic hepatitis C and diabetes: a novel triad
From the Metabolic Unit and 1Department of Medicine, Kaplan Medical Centre, Rehovot, Hebrew University Hadassah Medical School, Jerusalem, Israel
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)-
system has a pivotal role in the inflammatory process of chronic hepatitis C, and TNF- levels correlate with the degree of inflammation. TNF- 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- mRNA; all of which were ameliorated by anti-TNF- antibodies. In addition, diabetic HCV patients have significantly higher levels of soluble TNF- receptors, compared to non-diabetic HCV patients and controls. TNF- may be the link between HCV infection and diabetes, suggesting an additional mechanism of diabetes with important implications for prognosis and therapy.
Address correspondence to Professor A. Schattner, Department of Medicine, Addenbrooke's Hospital, University of Cambridge School of Clinical Medicine, Cambridge CB2 2QQ. e-mail: as655{at}medschl.cam.ac.uk or Dr H. Knobler, e-mail: knobler{at}inter.net.il
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