title: Increased serum soluble tumor necrosis factor receptor levels are associated with insulin resistance in liver cirrhosis.
abstract: Insulin resistance is present in nearly all patients with liver cirrhosis, but its etiology remains unclear. Recent studies have shown that tumor necrosis factor-alpha (TNF-alpha) system is involved in the insulin resistance of human obesity. Serum concentrations of TNF-alpha, and 2 soluble TNF receptors (sTNF-RI and sTNF-RII) are increased in cirrhotic patients. This study explored whether TNF-alpha system activity was associated with insulin resistance in liver cirrhosis. A total of 26 male nondiabetic patients with liver cirrhosis (mean age, 59 +/- 3 years; body mass index, 23.7 +/- 0.4 kg/m2) and 25 male control subjects (age, 65 +/- 2 years; body mass index, 24.4 +/- 0.5 kg/m2) were studied. Serum insulin, c-peptide, TNF-alpha, sTNF-RI, and sTNF-RII concentrations were determined by immunoassay. The insulin resistance was estimated by homeostasis assessment model (HOMA IR). In cirrhotic patients, serum levels of TNF-alpha, sTNF-RI, and sTNF-RII were all higher than those in the controls, and correlated with disease severity. Also, the serum c-peptide, insulin concentrations, and the HOMA IR were higher in liver cirrhosis with comparable blood glucose to control subjects, indicating a degree of insulin insensitivity. In the whole population, there was a moderate, but statistically significant, correlation between serum sTNF-RI or sTNF-RII, and HOMA IR. Also, body mass index was associated with HOMA IR, but not related to serum TNF-alpha, and sTNF-Rs levels. In multiple regression analysis, both sTNF-RII and body mass index jointly contributed to 30% variance of HOMA IR. Our study demonstrated that elevated sTNF-RII levels were associated with insulin resistance in liver cirrhosis. The data indicated that TNF-alpha system might play a role in modulating insulin action in patients with liver cirrhosis.
authors.affiliation: Division of Endocrinology and Metabolism, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Lin
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Wang
authors.forename: W-H H
authors.initials: WH
authors.lastname: Sheu
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology; D015992:Body Mass Index; D002096:C-Peptide / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007118:Immunoassay; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D015850:Interleukin-6 / Q000097:blood; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D012044:Regression Analysis
chemical_list: D002096:C-Peptide; D016207:Cytokines; D007328:Insulin; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor