title: Plasma proprotein convertase subtilisin kexin type 9 is not altered in subjects with impaired glucose metabolism and type 2 diabetes mellitus, but its relationship with non-HDL cholesterol and apolipoprotein B may be modified by type 2 diabetes mellitus: The CODAM study.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Division of General Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands. martijn.brouwers@maastrichtuniversity.nl
authors.forename: M C G J
authors.initials: MC
authors.lastname: Brouwers
authors.forename: J S
authors.initials: JS
authors.lastname: Troutt
authors.forename: M M J
authors.initials: MM
authors.lastname: van Greevenbroek
authors.forename: I
authors.initials: I
authors.lastname: Ferreira
authors.forename: E J
authors.initials: EJ
authors.lastname: Feskens
authors.forename: C J H
authors.initials: CJ
authors.lastname: van der Kallen
authors.forename: N C
authors.initials: NC
authors.lastname: Schaper
authors.forename: C G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: R J
authors.initials: RJ
authors.lastname: Konrad
authors.forename: C D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000368:Aged; D001055:Apolipoproteins B / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D048909:Diabetes Complications / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D050171:Dyslipidemias / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics* / Q000502:physiology*; D011446:Prospective Studies; D012044:Regression Analysis; D012697:Serine Endopeptidases / Q000235:genetics* / Q000502:physiology*; D014280:Triglycerides / Q000097:blood*
chemical_list: D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D005947:Glucose