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

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Taskinen , M-R , Björnson , E , Andersson , L , Kahri , J , Porthan , K , Matikainen , N , Söderlund , S , Pietiläinen , K , Hakkarainen , A , Lundbom , N , Nilsson , R , Stahlman , M , Adiels , M , Parini , P , Packard , C & Boren , J 2020 , ' 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 of Clinical Lipidology , vol. 14 , no. 1 , pp. 77-87 . https://doi.org/10.1016/j.jacl.2019.12.003

Title: Impact of proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab on the postprandial responses of triglyceride-rich lipoproteins in type II diabetic subjects
Author: Taskinen, Marja-Riitta; Björnson, Elias; Andersson, Linda; Kahri, Juhani; Porthan, Kimmo; Matikainen, Niina; Söderlund, Sanni; Pietiläinen, Kirsi; Hakkarainen, Antti; Lundbom, Nina; Nilsson, Ralf; Stahlman, Marcus; Adiels, Martin; Parini, Paolo; Packard, Chris; Boren, Jan
Contributor organization: HUS Heart and Lung Center
Clinicum
CAMM - Research Program for Clinical and Molecular Metabolism
Research Programs Unit
University of Helsinki
HUS Internal Medicine and Rehabilitation
Marja-Riitta Taskinen Research Group
Helsinki University Hospital Area
HUS Abdominal Center
Endokrinologian yksikkö
Department of Medicine
HUS Medical Imaging Center
Department of Diagnostics and Therapeutics
Date: 2020
Language: eng
Number of pages: 11
Belongs to series: Journal of Clinical Lipidology
ISSN: 1933-2874
DOI: https://doi.org/10.1016/j.jacl.2019.12.003
URI: http://hdl.handle.net/10138/323528
Abstract: 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.
Subject: 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
3121 General medicine, internal medicine and other clinical medicine
317 Pharmacy
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: acceptedVersion


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