Tumor necrosis factor—α—induced insulin resistance may mediate the hepatitis C virus—diabetes association

Knobler, Hula; Zhornicky, Taiba; Sandler, Alex; Haran, Nurit; Ashur, Yafa; Schattner, Ami
December 2003
American Journal of Gastroenterology;Dec2003, Vol. 98 Issue 12, p2751
Academic Journal
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-α (TNF-α) has been identified as a mediator of insulin resistance and is induced by HCV, we examined TNF-α 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-α, interleukin-1β (IL-1β), 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 HCVIDM patients, versus 64% of the nondiabetic HCV group and ≤ 10% in the other groups. Mean sTNFR1 in the HCVIDM 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 = 195 1-2784) in the nondiabetic HCV patients, and similar results in the other groups (p < 0.0001). Serum IL-1β, IL-6, and C-reactive protein were not significantly different between HCV patients with or without DM. CONCLUSIONS: Excessive TNF-α 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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