OBJECTIVE: Type 2 diabetes mellitus (T2DM) is associated with elevated plasma 
apolipoprotein B and triglycerides levels, reduced HDL cholesterol and the 
presence of small-dense LDL particles. The present study was conducted to 
investigate the role of plasma proprotein convertase subtilisin kexin type 9 
(PCSK9) levels, a regulator of LDL-receptor expression, in the occurrence of 
diabetic dyslipidemia.
METHODS: Plasma PCSK9 was measured in a cohort of subjects with normal glucose 
metabolism (NGM; n=288), impaired glucose metabolism (IGM; n=121) and type 2 
diabetes mellitus (T2DM; n=139) to study whether its relation with plasma 
apolipoprotein B, triglycerides, total cholesterol, non-HDL cholesterol, LDL 
cholesterol and HDL cholesterol differed by levels of glucose metabolism status.
RESULTS: Plasma PCSK9 levels were not different between the three groups (82, 82 
and 80 ng/mL in NGM, IGM and T2DM, respectively). PCSK9 was positively 
associated with total cholesterol, non-HDL cholesterol, LDL cholesterol, 
apolipoprotein B and triglycerides levels in all subgroups. The regression 
slopes for the associations with non-HDL cholesterol were steeper among 
individuals with T2DM than with NGM (β = 0.016 versus β=0.009, 
p-interaction=0.05). Similar results were obtained for the relation with 
apolipoprotein B (β = 0.004 versus β = 0.002, p-interaction=0.09).
CONCLUSIONS: Although glucose metabolism status per se is not associated with 
plasma PCSK9 levels, the presence of T2DM may modify the relation between plasma 
PCSK9 and non-HDL cholesterol and apolipoprotein B. These observations should be 
regarded as hypothesis generating for further studies aimed at elucidating the 
role of PCSK9 in the pathogenesis and treatment of diabetic dyslipidemia.