To the top

Page Manager: Webmaster
Last update: 9/11/2012 3:13 PM

Tell a friend about this page
Print version

Impact of proprotein conv… - University of Gothenburg, Sweden Till startsida
To content Read more about how we use cookies on

Impact of proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab on the postprandial responses of triglyceride-rich lipoproteins in type II diabetic subjects

Journal article
Authors M. R. Taskinen
Elias Björnson
Linda Andersson
J. Kahri
K. Porthan
N. Matikainen
S. Soderlund
K. Pietilainen
A. Hakkarainen
N. Lundbom
R. Nilsson
Marcus Ståhlman
Martin Adiels
P. Parini
C. Packard
Jan Borén
Published in Journal of Clinical Lipidology
Volume 14
Issue 1
Pages 77-87
ISSN 1933-2874
Publication year 2020
Published at Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 77-87
Language en
Keywords apoB, Postprandial lipids, Remnant lipoproteins, Apolipoprotein C3, Atherogenic dyslipidemia, De novo lipogenesis, Evolocumab, PCSK9, Liver, fat, atherosclerotic cardiovascular-disease, hmg-coa reductase, cholesterol, precursors, stable-isotope, fat-content, risk-factor, bile-acid, metabolism, hypertriglyceridemia, atorvastatin, Pharmacology & Pharmacy
Subject categories Molecular medicine, Pharmacology and Toxicology


BACKGROUND: Monoclonal antibodies to proprotein convertase subtilisin/kexin type 9 (PCSK9) significantly lower the levels of low-density lipoprotein and very-low-density lipoproteins (VLDL), but their effect on postprandial lipoprotein metabolism in dyslipidemic subjects is unclear. OBJECTIVE: This study aimed to investigate the effects of evolocumab on postprandial lipid responses, ectopic fat depots, whole-body cholesterol synthesis, hepatic lipogenesis, and fat oxidation in patients with type II diabetes. METHODS: The trial was a single-phase, nonrandomized study of 12-week treatment with evolocumab 140 mg subcutaneously every 2 weeks in 15 patients with type II diabetes on background statin therapy. Cardiometabolic responses to a high-fat mixed meal were assessed before and at the end of the intervention period. RESULTS: Evolocumab treatment reduced significantly postprandial rises in plasma total triglyceride (by 21%; P < .0001) and VLDL i triglyceride (by 15%; P = .018), but the increase in chylomicron triglyceride after the meal was not significantly perturbed (P = .053). There were reduced postprandial responses in plasma total apolipoprotein C-III (by 14%; P < .0001) and apolipoprotein B-48 concentration (by 17%; P = .0046) and in "remnant-like particles" cholesterol (by 29%; P < .0001) on the PCSK9 inhibitor. Treatment reduced the steady-state (ie, fasting and postprandial) concentrations of VLDL2 cholesterol by 50% (P < .0001) and VLDL2 triglyceride by 29% (P < .0001), in addition to the 78% reduction of low-density lipoprotein cholesterol (P < .001). The changes in apolipoprotein C-III associated significantly with reduction in postprandial responses of remnant-like particles cholesterol and triglyceride-rich lipoprotein cholesterol. Evolocumab therapy did not influence liver fat accumulation, hepatic de novo lipogenesis, or fasting beta-hydroxybutyrate but did increase total body cholesterol synthesis (P < .01). CONCLUSION: Evolocumab treatment improved postprandial responses of triglyceride-rich lipo-proteins and measures of cholesterol-enriched remnant particles in type II diabetic subjects. These results indicate that postprandial phenomena need to be taken into account in assessing the full range of actions of PCSK9 inhibitors in dyslipidemic individuals. (C) 2020 Published by Elsevier Inc. on behalf of National Lipid Association.

Page Manager: Webmaster|Last update: 9/11/2012

The University of Gothenburg uses cookies to provide you with the best possible user experience. By continuing on this website, you approve of our use of cookies.  What are cookies?