Editorial
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jul 15, 2017; 8(7): 311-316
Published online Jul 15, 2017. doi: 10.4239/wjd.v8.i7.311
PCSK9 and carbohydrate metabolism: A double-edged sword
Theodosios D Filippatos, Sebastian Filippas-Ntekouan, Eleni Pappa, Thalia Panagiotopoulou, Vasilios Tsimihodimos, Moses S Elisaf
Theodosios D Filippatos, Sebastian Filippas-Ntekouan, Eleni Pappa, Thalia Panagiotopoulou, Vasilios Tsimihodimos, Moses S Elisaf, Department of Internal Medicine, School of Medicine, University of Ioannina, 45110 Ioannina, Greece
Author contributions: Filippatos TD wrote the manuscript; Filippas-Ntekouan S and Panagiotopoulou T searched the bibliography; Pappa E, Tsimihodimos V and Elisaf MS made appropriate comments and checked the final version of the manuscript.
Conflict-of-interest statement: This review was written independently. Professor Elisaf MS reports personal fees from ASTRA ZENECA, grants and personal fees from MSD, personal fees from PFIZER, ABBOTT, SANOFI, BOEHRINGER INGELHEIM, ELI LILLY, GSK. The authors have given talks and attended conferences sponsored by various pharmaceutical companies, including Bristol-Myers Squibb, Pfizer, Lilly, Abbott, Amgen, AstraZeneca, Novartis, Vianex, Teva and MSD.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Moses S Elisaf, Professor, Department of Internal Medicine, School of Medicine, University of Ioannina, Staurou Niarchou Avenue, 45110 Ioannina, Greece. melisaf54@gmail.com
Telephone: +30-26-51007509 Fax: +30-26-51007016
Received: December 24, 2016
Peer-review started: December 28, 2016
First decision: February 17, 2017
Revised: February 27, 2017
Accepted: March 23, 2017
Article in press: March 24, 2017
Published online: July 15, 2017
Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a paramount role in the degradation of low-density lipoprotein (LDL) receptors (LDLR) on the hepatic cells surface and subsequently affects LDL particles catabolism and LDL cholesterol (LDL-c) levels. The anti-PCSK9 monoclonal antibodies lead to substantial decrease of LDL-c concentration. PCSK9 (which is also expressed in pancreatic delta-cells) can decrease LDLR and subsequently decrease cholesterol accumulation in pancreatic beta-cells, which impairs glucose metabolism and reduces insulin secretion. Thus, a possible adverse effect of PCSK9 inhibitors on carbohydrate metabolism may be expected by this mechanism, which has been supported by the mendelian studies results. On the other hand, clinical data have suggested a detrimental association of PCSK9 with glucose metabolism. So, the inhibition of PCSK9 may be seen as a double-edged sword regarding carbohydrate metabolism. Completed clinical trials have not shown a detrimental effect of PCSK9 inhibitors on diabetes risk, but their short-term duration does not allow definite conclusions.

Keywords: Proprotein convertase subtilisin/kexin type 9, Diabetes, Carbohydrate metabolism, Low-density lipoprotein, Proprotein convertase subtilisin/kexin type 9 inhibitors

Core tip: Proprotein convertase subtilisin/kexin type 9 (PCSK9) may play a beneficial role in carbohydrate metabolism because it can decrease low-density lipoprotein receptor and subsequently decrease cholesterol accumulation in pancreatic beta-cells, which impairs glucose metabolism and reduces insulin secretion. In contrast, clinical data have suggested a detrimental association of PCSK9 with glucose metabolism. These conflicting mechanisms may lead to a neutral effect on carbohydrate variables and explain the results of short-term clinical trials with PCSK9 inhibitors, which have not shown an increased diabetes risk.