Plasma proprotein convertase subtilisin/kexin type 9 is associated with Lp(a) in type 2 diabetic patients

Aim Recent in vitro researches have shown that plasma Lp(a) can be reduced using a proprotein convertase subtilisin/kexin type 9 (PCSK9)-inhibitory monoclonal antibody. In our clinical study we tried to investigate the association between plasma Lp(a) and PCSK9 in Type 2 diabetic patients with elevated plasma Lp(a), and to check whether such an association would be related to LDL-receptor (LDL-R) levels. Methods Plasma PCSK9 and LDL-R concentrations were measured by sandwich ELISA methods using recombinant human PCSK9 protein and LDL-R protein as standards in a cohort with type 2 diabetic patients (n = 50) compared to an age- and sex-matched control group (n = 50). Both clinical and biochemical parameters were determined in all patients. Results Plasma PCSK9 level was significantly elevated in T2DM patients 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. Remarkably, plasma PCSK9 levels were positively correlated with Lp(a) levels in whole population (r = + 0.227, P = 0.03) as well as in T2DM group (r = + 0.398, P = 0.0061) but not in control group. Multiple linear regression analysis showed that plasma Lp(a) levels were independently associated to those of PCSK9. Conclusion Lp(a) has been proposed as a contributing factor to the accelerated development of macrovascular complications in T2DM. Its synergic effect with PCSK9 may explain the enhanced atherogenicity in T2DM patients.