Effects of Evolocumab on the Postprandial Kinetics of Apo (Apolipoprotein) B100-and B48-Containing Lipoproteins in Subjects With Type 2 Diabetes

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Taskinen , MR , Bjornson , E , Kahri , J , Soderlund , S , Matikainen , N , Porthan , K , Ainola , M , Hakkarainen , A , Lundbom , N , Fermanelli , V , Fuchs , J , Thorsell , A , Kronenberg , F , Andersson , L , Adiels , M , Packard , CJ & Boren , J 2021 , ' Effects of Evolocumab on the Postprandial Kinetics of Apo (Apolipoprotein) B100-and B48-Containing Lipoproteins in Subjects With Type 2 Diabetes ' , Arteriosclerosis, Thrombosis, and Vascular Biology , vol. 41 , no. 2 , pp. 962-975 . https://doi.org/10.1161/ATVBAHA.120.315446

Title: Effects of Evolocumab on the Postprandial Kinetics of Apo (Apolipoprotein) B100-and B48-Containing Lipoproteins in Subjects With Type 2 Diabetes
Author: Taskinen, MR; Bjornson, E; Kahri, J; Soderlund, S; Matikainen, N; Porthan, K; Ainola, M; Hakkarainen, A; Lundbom, N; Fermanelli, V; Fuchs, J; Thorsell, A; Kronenberg, F; Andersson, L; Adiels, M; Packard, CJ; Boren, J
Contributor organization: HUS Medical Imaging Center
Clinicum
Research Programs Unit
HUS Internal Medicine and Rehabilitation
Marja-Riitta Taskinen Research Group
Doctoral Programme in Clinical Research
Endokrinologian yksikkö
Department of Medicine
HUS Abdominal Center
Date: 2021-02
Language: eng
Number of pages: 14
Belongs to series: Arteriosclerosis, Thrombosis, and Vascular Biology
ISSN: 1079-5642
DOI: https://doi.org/10.1161/ATVBAHA.120.315446
URI: http://hdl.handle.net/10138/335991
Abstract: OBJECTIVE: Increased risk of atherosclerotic cardiovascular disease in subjects with type 2 diabetes is linked to elevated levels of triglyceride-rich lipoproteins and their remnants. The metabolic effects of PCSK9 (proprotein convertase subtilisin/kexin 9) inhibitors on this dyslipidemia were investigated using stable-isotope-labeled tracers. APPROACH AND RESULTS: Triglyceride transport and the metabolism of apos (apolipoproteins) B48, B100, C-III, and E after a fat-rich meal were investigated before and on evolocumab treatment in 13 subjects with type 2 diabetes. Kinetic parameters were determined for the following: apoB48 in chylomicrons; triglyceride in VLDL1 (very low-density lipoprotein) and VLDL2; and apoB100 in VLDL1, VLDL2, IDL (intermediate-density lipoprotein), and LDL (low-density lipoprotein). Evolocumab did not alter the kinetics of apoB48 in chylomicrons or apoB100 or triglyceride in VLDL1. In contrast, the fractional catabolic rates of VLDL2-apoB100 and VLDL2-triglyceride were both increased by about 45%, which led to a 28% fall in the VLDL2 plasma level. LDL-apoB100 was markedly reduced by evolocumab, which was linked to metabolic heterogeneity in this fraction. Evolocumab increased clearance of the more rapidly metabolized LDL by 61% and decreased production of the more slowly cleared LDL by 75%. ApoC-III kinetics were not altered by evolocumab, but the apoE fractional catabolic rates increased by 45% and the apoE plasma level fell by 33%. The apoE fractional catabolic rates was associated with the decrease in VLDL2- and IDL-apoB100 concentrations. CONCLUSIONS: Evolocumab had only minor effects on lipoproteins that are involved in triglyceride transport (chylomicrons and VLDL1) but, in contrast, had a profound impact on lipoproteins that carry cholesterol (VLDL2, IDL, LDL).
Subject: apolipoprotein
cardiovascular diseases
chylomicrons
evolocumab
kinetics
TRIGLYCERIDE-RICH LIPOPROTEINS
PCSK9 INHIBITOR EVOLOCUMAB
SUBTILISIN/KEXIN TYPE 9
CARDIOVASCULAR-DISEASE
000 PARTICIPANTS
LDL CHOLESTEROL
REDUCING LIPIDS
EFFICACY
SAFETY
METABOLISM
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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