title: Tumor necrosis factor-alpha-induced insulin resistance may mediate the hepatitis C virus-diabetes association.
abstract: OBJECTIVE
  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.
authors.affiliation: Hebrew University and Hadassah Medical School, Department of Medicine, Kaplan Medical Center, Rehovot 76100, Israel.
authors.forename: Hilla
authors.initials: H
authors.lastname: Knobler
authors.forename: Taiba
authors.initials: T
authors.lastname: Zhornicky
authors.forename: Alex
authors.initials: A
authors.lastname: Sandler
authors.forename: Nurit
authors.initials: N
authors.lastname: Haran
authors.forename: Yafa
authors.initials: Y
authors.lastname: Ashur
authors.forename: Ami
authors.initials: A
authors.lastname: Schattner
mesh_terms: D000704:Analysis of Variance; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000209:etiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications*; D006801:Humans; D007333:Insulin Resistance; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha