title: Association of secreted frizzled-related protein 4 (SFRP4) with type 2 diabetes in patients with stable coronary artery disease.
abstract: BACKGROUND
  Secreted frizzled-related proteins (SFRP) are regulators of Wnt-signalling. SFRP4 has been shown to regulate insulin exocytosis and is overexpressed in type 2 diabetes mellitus. Here we characterized the relation of SFRP4 to glucose and triglyceride metabolism and outcomes in patients with stable coronary artery disease on statin treatment in the prospective Homburg Cream & Sugar Study (NCT00628524).
  
  
  METHODS
  Fasting SFRP4 concentrations were measured by ELISA in 504 consecutive patients with stable CAD confirmed by angiography.
  
  
  RESULTS
  The median age was 68 years and 83% of patients were male. Oral glucose tolerance tests were performed in all patients without known diabetes for metabolic characterization. 24.4% of patients showed normal glucose tolerance, 29.4% impaired glucose tolerance and 46.2% diabetes mellitus. SFRP4 concentrations correlated with insulin (R = 0.153, p = 0.001), HbA1c (R = 0.166, p < 0.0001), fasting triglycerides (R = 0.113, p = 0.011) and higher triglycerides after lipid challenge (postprandial triglycerides R = 0.124, p = 0.005; AUC R = 0.134, p = 0.003). Higher SFRP4 concentrations were associated with type 2 diabetes, metabolic syndrome, and severity of diabetes. The primary outcome was the composite of cardiovascular death and cardiovascular hospitalization within 48 months follow-up. Comparison of event-free survival between SFRP4 tertiles showed that SFRP4 concentrations were not predictive for cardiovascular outcome.
  
  
  CONCLUSIONS
  SFRP4 concentrations are associated with impaired glucose and triglyceride metabolism but do not predict cardiovascular outcome in patients with stable coronary artery disease on treatment.
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Freiburg, Freiburg, Germany. michael.marcus.hoffmann@uniklinik-freiburg.de.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hoffmann
authors.affiliation: Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg, Germany. christian.werner@uks.eu.
authors.forename: Christian
authors.initials: C
authors.lastname: Werner
authors.affiliation: Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg, Germany. Michael.Boehm@uniklinikum-saarland.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.affiliation: Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg, Germany. Ulrich.laufs@uks.eu.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Laufs
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Freiburg, Freiburg, Germany. karl.winkler@uniklinik-freiburg.de.
authors.forename: Karl
authors.initials: K
authors.lastname: Winkler
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003324:Coronary Artery Disease / Q000150:complications / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D001786:Blood Glucose; D011518:Proto-Oncogene Proteins; D014280:Triglycerides; C118723:SFRP4 protein, human; D000094742:Secreted Frizzled-Related Proteins