Serum Fetuin-A is an Independent Marker of Insulin Resistance in Japanese Men

Abstract

Fetuin-A, also known as alpha2-Heremans Schmid glycoprotein, is an abundant plasma protein synthesized predominantly in the liver. Fetuin-A inhibits insulin receptor autophosphorylation, which is mediated by its intrinsic tyrosine kinase activity. In this study, we examined the association between the serum fetuin-A level and insulin resistance in Japanese men. We recruited 300 unrelated Japanese men without known chronic diseases, such as diabetes mellitus, or a history of regular drug use, and who underwent health examinations. From a 75-g oral glucose tolerance test, the study population included 194 individuals with normal glucose tolerance, 91 with impaired glucose tolerance and/or impaired fasting glucose, and 15 with diabetes mellitus. Serum fetuin-A concentrations were measured using an ELISA kit. Serum fetuin-A concentrations were positively correlated with fasting insulin levels (r = 0.269, p<0.001), HOMA-IR (r = 0.274, p<0.001) and LDL-cholesterol (r = 0.172, p<0.01), and negatively correlated with HDL-cholesterol concentrations (r = -0.191, p<0.001). Fetuin-A concentrations were also positively correlated with serum leptin (r = 0.150, p<0.01) and negatively with adiponectin concentrations (r = -0.208, p<0.001). Stepwise regression analyses confirmed that the fetuin-A concentration was independently associated with the fasting insulin level and HOMA-IR, as were body mass index, triglyceride, LDL-cholesterol, leptin and adiponectin concentrations. Our data suggest that increased serum fetuin-A levels constitute an independent marker of insulin resistance and an atherogenic lipid profile in Japanese men.