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.