title: Lack of association between plasma PCSK9 and LDL-apoB100 catabolism in patients with uncontrolled type 2 diabetes.
abstract: OBJECTIVE
  Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is a post-transcriptional inhibitor of LDL-receptor. In non-diabetic men, plasma PCSK9 levels were found to be inversely correlated with low-density lipoprotein (LDL) apolipoprotein B100 (apoB) fractional catabolic rate (FCR). Here, we aimed to determine the effect of type 2 diabetes on the association between plasma PCSK9 and FCR of LDL.
  
  
  METHODS
  A kinetic study of LDL-apoB100, using stable isotopes, was performed in 38 individuals (20 men, 18 women) including 23 non-diabetic normolipidemic subjects and 15 patients with type 2 diabetes.
  
  
  RESULTS
  In the non-diabetic group, plasma PCSK9 was positively correlated with LDL-C (r=0.64, p=0.001), apoB (r=0.67, p<0.001), and inversely correlated with LDL-apoB FCR (r=-0.61, p=0.002). In contrast, in type 2 diabetic patients, plasma PCSK9 was not associated with LDL-C, apoB and LDL-apoB FCR. However, the lack of association between PCSK9 and LDL-apoB FCR seemed to be limited to the patients with "uncontrolled" diabetes (HbA1c>7%) since a borderline significant negative correlation between PCSK9 and LDL FCR (r=-0.70, p=0.08) was retrieved in patients with HbA1c≤7%. In multivariate analysis, LDL-apoB FCR was independently associated with PCSK9 (p=0.001) and fasting glycaemia (log) (p=0.030) in the non-diabetic population and with PCSK9 (p=0.040) and HbA1c (p=0.029) in diabetic patients.
  
  
  CONCLUSIONS
  Our data indicate that both PCSK9 and glycaemia are independent factors influencing LDL catabolism. Plasma PCSK9 influences significantly the catabolism of LDL-apoB100 in individuals without diabetes, but not in patients with uncontrolled type 2 diabetes. Thus, the influence of diabetes on LDL-apoB FCR catabolism may overwhelm the influence of PCSK9.
authors: INSERM CRI 866, CHU Bocage, Dijon, France. bruno.verges@chu-dijon.fr
authors: Bruno
authors: B
authors: Vergès
authors: Laurence
authors: L
authors: Duvillard
authors: Marie Claude
authors: MC
authors: Brindisi
authors: Emmanuel
authors: E
authors: Gautier
authors: Michel
authors: M
authors: Krempf
authors: Philippe
authors: P
authors: Costet
authors: Bertrand
authors: B
authors: Cariou
mesh_terms: D000328:Adult; D000368:Aged; D053299:Apolipoprotein B-100 / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood*; D012697:Serine Endopeptidases / Q000097:blood*
chemical_list: D053299:Apolipoprotein B-100; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases