Effects of Evolocumab on the Postprandial Kinetics of Apo (Apolipoprotein) B100- and B48-Containing Lipoproteins in Subjects With Type 2 Diabetes.
Artikel i vetenskaplig tidskrift, 2021

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.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). Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02948777.

Författare

Marja-Riitta Taskinen

Helsingin Yliopisto

Elias Björnson

Göteborgs universitet

Juhani Kahri

Helsingin Yliopisto

Sanni Söderlund

Helsinki University Central Hospital

Helsingin Yliopisto

Niina Matikainen

Helsingin Yliopisto

Helsinki University Central Hospital

Kimmo Porthan

Helsingin Yliopisto

Mari Ainola

Helsingin Yliopisto

Antti Hakkarainen

Aalto-Yliopisto

Helsinki University Central Hospital

Nina Lundbom

Helsinki University Central Hospital

Valentina Fermanelli

Chalmers, Matematiska vetenskaper, Analys och sannolikhetsteori

Göteborgs universitet

Johannes Fuchs

Göteborgs universitet

Annika Thorsell

Göteborgs universitet

Florian Kronenberg

Medizinische Universität Innsbruck

Linda Andersson

Göteborgs universitet

Martin Adiels

Matematik

Göteborgs universitet

Chris J. Packard

University of Glasgow

Jan Boren

Sahlgrenska universitetssjukhuset

Göteborgs universitet

Arteriosclerosis, Thrombosis, and Vascular Biology

1079-5642 (ISSN) 1524-4636 (eISSN)

Vol. 41 2 962-975

Ämneskategorier (SSIF 2025)

Kardiologi och kardiovaskulära sjukdomar

Endokrinologi och diabetes

DOI

10.1161/ATVBAHA.120.315446

PubMed

33356392

Mer information

Senast uppdaterat

2025-06-27