TNF-{alpha}, chronic hepatitis C and diabetes: a novel triad.
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.
Knobler
H
H
Department of Medicine, Addenbrooke's Hospital, University of Cambridge School of Clinical Medicine, Cambridge CB2 2QQ, UK.
Schattner
A
A
D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology / Q000821:virology*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000503:physiopathology; D006801:Humans; D007333:Insulin Resistance; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha