High serum Fetuin-B levels are associated with the presence of metabolic syndrome in women: a case-controlled study and interventional studies

Abstract Background: Previous studies have investigated circulating fetuin-B and its association with type 2 diabetes mellitus (T2DM). However, the variation and regulatory factors of serum fetuin-B levels in individuals with metabolic syndrome (MetS) have not been explained. This study evaluated circulating fetuin-B concentrations in newly diagnosed individuals with MetS and analyzed the impacts of blood glucose, insulin, and glucagon-like peptide-1 receptor agonists (GLP-1RA) treatment on circulating fetuin-B in vivo . Methods: A total of 377 women (192 MetS and 185 healthy subjects) were recruited for cross-sectional study. The euglycemic-hyperinsulinemic clamp (EHC) and oral glucose tolerance test (OGTT) were implemented in healthy women and those with MetS. Serum fetuin-B were examined by an ELISA kit. For the GLP-1RA intervention experiment, twenty-four women with MetS were treated with Liraglutide for 6 months. Results: Serum fetuin-B levels were markedly higher in women with MetS as compared to healthy women. Circulating fetuin-B reflected a positive correlation with body mass index, waist hip ratio (WHR), the percentage of fat in vivo (FAT%), triglyceride, fasting blood glucose, 2-hour blood glucose after glucose overload, glycosylated hemoglobin, fasting plasma insulin, 2-hour plasma insulin after glucose overload, homeostasis model assessment of insulin resistance (HOMA-IR), visceral adiposity index (VAI), and lipid accumulation product (LAP). Multivariate linear regression analyses demonstrated that triglyceride and WHR were independently related factors of serum fetuin-B. Serum fetuin-B levels were related to MetS by binary logistic regression analysis. In fact, serum fetuin-B was markedly elevated in healthy women after glucose loading and in MetS women during the EHC. After six months of GLP-1RA intervention, serum fetuin-B levels in MetS subjects decreased following improvement of metabolism and insulin sensitivity. Conclusions: Serum fetuin-B levels were associated with MetS and its components and regulated by glucose and insulin. GLP-1RA treatment can reduce serum fetuin-B levels in women with MetS. Clinical Trial Registration Number: ChiCTR-OCS-13003185. Registered 02/01 2016, http://www.chictr.org.cn/showproj.aspx?proj=6374