Increased serum soluble tumor necrosis factor receptor levels are associated with insulin resistance in liver cirrhosis

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.