title: Circulating PCSK9 in patients with type 2 diabetes and related metabolic disorders.
abstract: BACKGROUND
  PCSK9 is a pivotal molecule in the regulation of lipid metabolism. Previous studies have suggested that PCSK9 expression and its function in LDL receptor regulation could be altered in the context of diabetes. The aim was to assess PCSK9 plasma levels in patients with type 2 diabetes (T2DM) and other related metabolic disorders as well as its relation to the metabolomic profile generated by nuclear magnetic resonance (NMR) and glucose homeostasis.
  
  
  METHODS
  There were recruited a total of 457 patients suffering from T2DM and other metabolic disorders (metabolic syndrome (MetS), obesity and atherogenic dyslipidaemia (AD) and other disorders). Anamnesis, anthropometry and physical examinations were conducted, and vascular and abdominal adiposity imaging were carried out. Biochemical studies were performed to determine PCSK9 plasma levels 6 weeks after lipid lowering drug wash-out in treated patients. A complete metabolomic lipid profile was also generated by NMR. The rs505151 and rs11591147 genetic variants of PCSK9 gene were identified in patients.
  
  
  RESULTS
  The results showed that PCSK9 levels are increased in patients with T2DM and MetS (14% and 13%; p<0.005, respectively). Circulating PCSK9 levels were correlated with an atherogenic lipid profile and with insulin resistance parameters. PCSK9 levels were also positively associated with AD, as defined by lipoprotein particle number and size. The rs11591147 genetic variant resulted in lower levels of circulating PCSK9 and LDL cholesterol (LDL-C).
  
  
  CONCLUSIONS
  PCSK9 plasma levels are increased in T2DM and MetS patients and are associated with LDL-C and other parameters of AD and glucose metabolism.
authors.affiliation: Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira i Virgili, IISPV, Reus, Spain; Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.
authors.forename: Daiana
authors.initials: D
authors.lastname: Ibarretxe
authors.affiliation: Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira i Virgili, IISPV, Reus, Spain; Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.
authors.forename: Josefa
authors.initials: J
authors.lastname: Girona
authors.affiliation: Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira i Virgili, IISPV, Reus, Spain; Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Plana
authors.affiliation: Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira i Virgili, IISPV, Reus, Spain; Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Cabré
authors.affiliation: Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira i Virgili, IISPV, Reus, Spain; Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.
authors.forename: Raimón
authors.initials: R
authors.lastname: Ferré
authors.affiliation: Biosfer Teslab, Reus and Department of Electronic Engineering, Universitat Rovira i Virgili, IISPV, Tarragona, Spain; Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Amigó
authors.affiliation: Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira i Virgili, IISPV, Reus, Spain; Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Guaita
authors.affiliation: Biosfer Teslab, Reus and Department of Electronic Engineering, Universitat Rovira i Virgili, IISPV, Tarragona, Spain; Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.
authors.forename: Roger
authors.initials: R
authors.lastname: Mallol
authors.affiliation: Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira i Virgili, IISPV, Reus, Spain; Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Heras
authors.affiliation: Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira i Virgili, IISPV, Reus, Spain; Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain. Electronic address: luis.masana@urv.cat.
authors.forename: Luis
authors.initials: L
authors.lastname: Masana
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D050171:Dyslipidemias / Q000097:blood; D005260:Female; D014644:Genetic Variation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008659:Metabolic Diseases / Q000097:blood*; D024821:Metabolic Syndrome / Q000097:blood*; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D000071449:Proprotein Convertase 9 / Q000097:blood* / Q000235:genetics
chemical_list: D008078:Cholesterol, LDL; D008055:Lipids; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D005947:Glucose
keywords: Diabetes tipo 2; Metabolic syndrome; Nuclear magnetic resonance; PCSK9; Resonancia magnética nuclear; SNP; Síndrome metabólico; Type 2 diabetes