Increased fetuin-A concentrations in impaired glucose tolerance with or without nonalcoholic fatty liver disease, but not impaired fasting glucose

Context: Fetuin-A, a liver-derived glycoprotein that impairs insulin signaling, is associated with nonalcoholic fatty liver disease (NAFLD), diabetes, and the risk of cardiovascular diseases. Both prediabetes and NAFLD are associated with increased cardiovascular risk, and their concurrence significantly impairs hepatic and adipose tissue insulin sensitivity. Objective: Our objective was to investigate the relationship between serum fetuin-A levels and prediabetes in subjects with or without NAFLD. Design: This was a cross-sectional case-control study. Patients: A total of 510 age- and sex-matched subjects with normal glucose tolerance (NGT), impaired fasting glucose (IFG), and impaired glucose tolerance (IGT) with or without NAFLD were recruited. Each subject was assessed by abdominal ultrasound to diagnose NAFLD. Main Outcome Measures: Serum fetuin-A concentrations were compared between groups. The association with clinico-metabolic parameters was examined. Results: The presence of NAFLD significantly increases fetuin-A levels in subjects with NGT and prediabetes. As compared with NGT, IGT, but not IFG, significantly increases fetuin-A levels in subjects with or without NAFLD. Serum fetuin-A concentrations were positively related to postload 2-h glucose, body mass index, triglyceride, and homeostasis model assessment of insulin resistance but negatively associated with age, high-density lipoprotein cholesterol, and adiponectin. In multiple regression analysis, age, IGT vs. NGT, and IGT with NAFLD vs. NGT were independently associated with fetuin-A levels after adjustment for cardiovascular risk factors and adiponectin. Conclusions: IGT with or without NAFLD was independently associated with fetuin-A levels after adjustment for cardiometabolic risk factors. The elevated fetuin-A levels could have a clinical implication in the increased cardiovascular risk and insulin resistance associated with NAFLD and IGT.