Literature DB >> 14687828

Tumor necrosis factor-alpha-induced insulin resistance may mediate the hepatitis C virus-diabetes association.

Hilla Knobler1, Taiba Zhornicky, Alex Sandler, Nurit Haran, Yafa Ashur, Ami Schattner.   

Abstract

OBJECTIVES: Among patients infected with hepatitis C virus (HCV), 13-33% develop type 2 diabetes mellitus (DM). The mechanism for this remains unclear. Because tumor necrosis factor-alpha (TNF-alpha) has been identified as a mediator of insulin resistance and is induced by HCV, we examined TNF-alpha and proinflammatory cytokines in noncirrhotic patients with chronic hepatitis C, both with and without diabetes.
METHODS: HCV-infected patients with type 2 DM (n = 23) were compared with age- and sex-matched patients with chronic hepatitis C and without DM (n = 28), patients with DM and without HCV (n = 31), and healthy controls (n = 21). Serum levels of TNF-alpha, interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and soluble TNF receptors (sTNFR) 1 (p55) and 2 (p75) were determined by ELISA.
RESULTS: Detectable serum TNF was found in 74% of the HCV/DM patients, versus 64% of the nondiabetic HCV group and < or =10% in the other groups. Mean sTNFR1 in the HCV/DM group was 1931 pg/ml (95% CI = 1449-2413), compared with 1289 pg/ml (95% CI = 1101-1476) in nondiabetic HCV patients, with similar values in the other two groups (p = 0.001). The mean sTNFR2 level in the HCV/DM patients was 3326 pg/ml (95% CI = 2924-3727) compared with 2367 pg/ml (95% CI = 1951-2784) in the nondiabetic HCV patients, and similar results in the other groups (p < 0.0001). Serum IL-1beta, IL-6, and C-reactive protein were not significantly different between HCV patients with or without DM.
CONCLUSIONS: Excessive TNF-alpha response characterizes HCV-infected patients who develop DM. STNFR may be a marker for the development of DM in chronic hepatitis C.

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Year:  2003        PMID: 14687828     DOI: 10.1111/j.1572-0241.2003.08728.x

Source DB:  PubMed          Journal:  Am J Gastroenterol        ISSN: 0002-9270            Impact factor:   10.864


  42 in total

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