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

Autor: Martin Adiels, Kimmo Porthan, Johannes Fuchs, Annika Thorsell, Niina Matikainen, Sanni Söderlund, Valentina Fermanelli, Jan Borén, Linda Andersson, Chris J. Packard, Antti Hakkarainen, Mari Ainola, Florian Kronenberg, Marja-Riitta Taskinen, Juhani Kahri, Nina Lundbom, Elias Björnson
Přispěvatelé: 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
Rok vydání: 2020
Předmět:
Male
Time Factors
Apolipoprotein B
Cholesterol
VLDL
Type 2 diabetes
030204 cardiovascular system & hematology
Lipoproteins
VLDL
0302 clinical medicine
Medicine
biology
Atherosclerotic cardiovascular disease
Anticholesteremic Agents
PCSK9 Inhibitors
Middle Aged
Postprandial Period
3. Good health
000 PARTICIPANTS
Postprandial
Cholesterol
Treatment Outcome
CARDIOVASCULAR-DISEASE
SAFETY
Apolipoprotein B-100
lipids (amino acids
peptides
and proteins)
Female
Proprotein Convertase 9
Cardiology and Cardiovascular Medicine
REDUCING LIPIDS
PCSK9 INHIBITOR EVOLOCUMAB
Adult
medicine.medical_specialty
Serine Proteinase Inhibitors
Adolescent
Lipoproteins
Chylomicron Remnants
apolipoprotein
030209 endocrinology & metabolism
METABOLISM
Antibodies
Monoclonal
Humanized
03 medical and health sciences
Young Adult
Internal medicine
Humans
Triglycerides
Aged
Dyslipidemias
business.industry
SUBTILISIN/KEXIN TYPE 9
Metabolism
Cholesterol
LDL
EFFICACY
medicine.disease
Dietary Fats
cardiovascular diseases
Evolocumab
Kinetics
Endocrinology
Increased risk
evolocumab
Diabetes Mellitus
Type 2
3121 General medicine
internal medicine and other clinical medicine
biology.protein
chylomicrons
LDL CHOLESTEROL
business
Apolipoprotein B-48
TRIGLYCERIDE-RICH LIPOPROTEINS
Biomarkers
Chylomicron
Zdroj: Arteriosclerosis, thrombosis, and vascular biology. 41(2)
ISSN: 1524-4636
Popis: 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 VLDL 1 (very low-density lipoprotein) and VLDL 2 ; and apoB100 in VLDL 1 , VLDL 2 , IDL (intermediate-density lipoprotein), and LDL (low-density lipoprotein). Evolocumab did not alter the kinetics of apoB48 in chylomicrons or apoB100 or triglyceride in VLDL 1 . In contrast, the fractional catabolic rates of VLDL 2 -apoB100 and VLDL 2 -triglyceride were both increased by about 45%, which led to a 28% fall in the VLDL 2 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 VLDL 2 - and IDL-apoB100 concentrations. Conclusions: Evolocumab had only minor effects on lipoproteins that are involved in triglyceride transport (chylomicrons and VLDL 1 ) but, in contrast, had a profound impact on lipoproteins that carry cholesterol (VLDL 2 , IDL, LDL). Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02948777.
Databáze: OpenAIRE
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