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

Serum Fetuin-B Levels Are Elevated in Women with Metabolic Syndrome and Associated with Increased Oxidative Stress

“…Our study has some limitations: (1) considering the cross-sectional design of this study, our results do not prove causal relationships; (2) we included a relatively small sample size, particularly in intervention experiments; therefore, our data may be affected by outliers; (3) this cohort included only Chinese women and did not include men. Therefore, our findings should be applied cautiously to other ethnic 14 Oxidative Medicine and Cellular Longevity populations; and (4) the study failed to investigate the specific signal pathways by which fetuin-B affects hepatocytes. However, we included patients who were newly diagnosed with MetS and those without any lifestyle intervention and drug treatments, thereby avoiding the interference of disease course and other confounding factors.…”

“…In this study, we measured serum fetuin-B levels in healthy individuals and women newly diagnosed with MetS. A preprint for this part of the study has been published [ 14 ]. To investigate the association between serum fetuin-B and MetS as well as IR, we performed multiple intervention experiments, including euglycemic-hyperinsulinemic clamps (EHCs), oral glucose tolerance tests (OGTTs), and treatment with a glucagon-like peptide-1 receptor agonist (GLP-1RA).…”