Plasma proprotein convertase subtilisin/Kexin type 9 (PCSK9) is associated with Lp(a) in non-CAD type 2 diabetic patients

Abstract

Type 2 diabetes mellitus (T2DM) is associated with elevated plasma apolipoprotein B, Lp(a), triglycerides and reduced HDL-C. The present study was conducted to investigate whether plasma proprotein convertase subtilisin/kexin type 9 (PCSK9), a regulator of LDL-receptor (LDLr) expression in hepatocytes, was associated with diabetic dyslipidemia. We developed a sandwich ELISA using recombinant human PCSK9 protein and a polyclonal antibody pre-coated onto a microplate specific directed against human PCSK9. We measured circulating PCSK9 concentrations in a cohort of patients with T2DM ( n = 50) compared to an age- and sex-matched control group ( n = 50). Plasma apolipoprotein B, Lp(a) triglycerides, LDL-C, HDL-C and LDL-r were measured in both groups. Plasma PCSK9 levels were significantly elevated in T2DM compared to controls (44.61 ± 14.44 and 33.22 ± 11.79 ng/mL respectively, P < 0.0001). However, LDL-r levels did not differ between the two groups. No significant correlation of PCSK9 with lipid parameters was found. Remarkably PCSK9 was positively correlated with Lp(a) in whole population ( r = +0.254, P < 0.0138) and T2DM group ( r = +0287, P = 0.0474) but not in controls. Lp(a) levels has been proposed as a contributing factor to the accelerated development of macrovascular complications in T2DM and the synergic effect with PCSK9 may explain the enhanced atherogenicity in type 2 diabetic patients.