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- Title
TNF-a, chronic hepatitis C and diabetes: a novel triad.
- Authors
H. Knobler; A. Schattner
- Abstract
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)-a system has a pivotal role in the inflammatory process of chronic hepatitis C, and TNF-a levels correlate with the degree of inflammation. TNF-a 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-a mRNA; all of which were ameliorated by anti-TNF-a antibodies. In addition, diabetic HCV patients have significantly higher levels of soluble TNF-a receptors, compared to non-diabetic HCV patients and controls. TNF-a may be the link between HCV infection and diabetes, suggesting an additional mechanism of diabetes with important implications for prognosis and therapy.
- Subjects
HEPATITIS C; DIABETES; HYPOGLYCEMIC agents; INSULIN; DIABETES complications
- Publication
QJM: An International Journal of Medicine, 2005, Vol 98, Issue 1, p1
- ISSN
1460-2725
- Publication type
Article
- DOI
10.1093/qjmed/hci001