Effects of Evolocumab on the Postprandial Kinetics of Apo (Apolipoprotein) B100- and B48-Containing Lipoproteins in Subjects With Type 2 Diabetes.
Journal article, 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.
Author
Marja-Riitta Taskinen
University of Helsinki
Elias Björnson
University of Gothenburg
Juhani Kahri
University of Helsinki
Sanni Söderlund
Helsinki University Central Hospital
University of Helsinki
Niina Matikainen
University of Helsinki
Helsinki University Central Hospital
Kimmo Porthan
University of Helsinki
Mari Ainola
University of Helsinki
Antti Hakkarainen
Aalto University
Helsinki University Central Hospital
Nina Lundbom
Helsinki University Central Hospital
Valentina Fermanelli
Chalmers, Mathematical Sciences, Analysis and Probability Theory
University of Gothenburg
Johannes Fuchs
University of Gothenburg
Annika Thorsell
University of Gothenburg
Florian Kronenberg
Medical University of Innsbruck
Linda Andersson
University of Gothenburg
Martin Adiels
Mathematics
University of Gothenburg
Chris J. Packard
University of Glasgow
Jan Boren
Sahlgrenska University Hospital
University of Gothenburg
Arteriosclerosis, Thrombosis, and Vascular Biology
1079-5642 (ISSN) 1524-4636 (eISSN)
Vol. 41 2 962-975Subject Categories (SSIF 2025)
Cardiology and Cardiovascular Disease
Endocrinology and Diabetes
DOI
10.1161/ATVBAHA.120.315446
PubMed
33356392