title: Proinflammatory cytokines, insulin resistance, and insulin secretion in chronic hepatitis C patients: A case-control study.
abstract: OBJECTIVE
  The purpose of this study was to explore the initial pathogenic mechanisms of diabetes associated with hepatitis C virus (HCV) infection.
  
  
  METHODS
  Insulin resistance, proinflammatory cytokines, and beta-cell function were evaluated in a case-control study. A total of 28 consecutive nondiabetic patients with chronic hepatitis C were included in the study (anti-HCV+). Fourteen patients with chronic hepatitis other than HCV infection served as the control group (anti-HCV-). Both groups were closely matched by the main clinical variables associated with insulin resistance and the degree of liver fibrosis. In addition, there were no differences between groups regarding hepatic insulin extraction measured by calculating the ratio between C-peptide and insulin. Serum levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha, soluble TNF receptor [sTNFR] 1, soluble TNFR2, and interleukin-6) were measured by enzyme-linked immunosorbent assay. Insulin resistance (homeostasis model assessment [HOMA] of insulin resistance [HOMA-IR]) and insulin secretion at baseline (HOMA-beta) and after various stimulus (oral glucose tolerance test, standard food intake, and intravenous glucagon) were determined by previously validated mathematic indexes.
  
  
  RESULTS
  HOMA-IR was higher in anti-HCV+ than in anti-HCV- patients (4.35 +/- 2.27 vs. 2.58 +/- 1.74; P = 0.01). All the proinflammatory cytokines analyzed were significantly higher in anti-HCV+ patients than in anti-HCV- patients. In addition, sTNFR1 and sTNFR2 were directly correlated to HOMA-IR. HOMA-beta as well as insulin and C-peptide responses after the intravenous glucagon test were significantly higher in anti-HCV+ patients than in anti-HC- patients.
  
  
  CONCLUSIONS
  Insulin resistance mediated by proinflammatory cytokines, but not a deficit in insulin secretion, could be the primary pathogenic mechanism involved in the development of diabetes associated with HCV infection.
authors.affiliation: Diabetes Research Unit. Endocrinology Division, Institut de Recerca, Hospital Universitari Vall d'Hebron, Pg. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Lecube
authors.forename: Cristina
authors.initials: C
authors.lastname: Hernández
authors.forename: Joan
authors.initials: J
authors.lastname: Genescà
authors.forename: Rafael
authors.initials: R
authors.lastname: Simó
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002096:C-Peptide / Q000097:blood; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood
chemical_list: D002096:C-Peptide; D016207:Cytokines; D007328:Insulin; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II