title: The Effect of Proprotein Convertase Subtilisin-Kexin Type 9 and its Inhibition on Glucose Metabolism and Cardiovascular Risk. We Should do Better the Second Time After Statins.
abstract: Statins remain the cornerstone of hypolipidaemic drug treatment. However, statins exert adverse effects on glucose metabolism. Given that new onset diabetes mellitus (NODM) and worsening of glucose control in patients with established type 2 diabetes mellitus (T2DM) is related to low density lipoprotein cholesterol (LDL-C) reduction, it would be of great interest to investigate if this is also the case for proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, which have recently be licensed for the treatment of hypercholesterolaemia.
  
  
  
  We reviewed the published papers on the relation between circulating PCSK9 and diabetogenesis.
  
  
  
  Recent data suggest that increased circulating PCSK9 levels, besides causing dyslipidaemia, are related to increased glucose levels, metabolic syndrome, and even T2DM. On the contrary, fasting plasma glucose and HbA1c levels are not adversely affected during treatment with human antibodies against PCSK9 in patients at low risk for T2DM, in patients at high risk of T2DM and in patients with established T2DM. Plasma lipoproteins (mainly LDL-C reduction) are similarly affected in patients with or without T2DM, and recent data suggest that PCSK9 inhibition might reduce cardiovascular events in patients with T2DM at least as much as in those without T2DM.
  
  
  
  The use of PCSK9 inhibitors appears to be related to a substantial clinical benefit without adversely affecting glucose metabolism and without increasing the incidence of NODM. Large ongoing studies will have to confirm these findings before expanding the use of these agents.
authors.affiliation: Head of Metabolic Disease Units, 2nd Pop. Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocrates Hospital, Thessaloniki, Greece. 15 Marmara St, Thessaloniki, 55132, Greece.
authors.forename: Vasilios G
authors.initials: VG
authors.lastname: Athyros
authors.affiliation: First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tziomalos
authors.affiliation: Department of Veterans Affairs and George Washington University, VA Medical Centre, 50 Irving Street, NW-151-E, Washington, DC 20422, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Doumas
authors.affiliation: 424 Military Hospital of Thessaloniki, Thessaloniki, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Sfikas
authors.affiliation: Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece.
authors.forename: Asterios
authors.initials: A
authors.lastname: Karagiannis
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology*; D000924:Anticholesteremic Agents / Q000737:chemistry / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D008078:Cholesterol, LDL / Q000037:antagonists & inhibitors / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000737:chemistry / Q000494:pharmacology; D000091362:PCSK9 Inhibitors; D000071449:Proprotein Convertase 9 / Q000097:blood / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D000091362:PCSK9 Inhibitors; D015842:Serine Proteinase Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D005947:Glucose
keywords: PCSK9 antibodies; cardiovascular risk; dyslipidaemia; glucose metabolism; new onset diabetes; statins