Effects of liraglutide on the metabolism of triglyceride-rich lipoproteins in type 2 diabetes

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Taskinen , M-R , Björnson , E , Matikainen , N , Söderlund , S , Pietiläinen , K H , Ainola , M , Hakkarainen , A , Lundbom , N , Fuchs , J , Thorsell , A , Andersson , L , Adiels , M , Packard , C J & Boren , J 2021 , ' Effects of liraglutide on the metabolism of triglyceride-rich lipoproteins in type 2 diabetes ' , Diabetes, obesity and metabolism , vol. 23 , no. 5 , pp. 1191-1201 . https://doi.org/10.1111/dom.14328

Title: Effects of liraglutide on the metabolism of triglyceride-rich lipoproteins in type 2 diabetes
Author: Taskinen, Marja-Riitta; Björnson, Elias; Matikainen, Niina; Söderlund, Sanni; Pietiläinen, Kirsi H.; Ainola, Mari; Hakkarainen, Antti; Lundbom, Nina; Fuchs, Johannes; Thorsell, Annika; Andersson, Linda; Adiels, Martin; Packard, Chris J.; Boren, Jan
Contributor organization: Clinicum
HUS Heart and Lung Center
Department of Medicine
CAMM - Research Program for Clinical and Molecular Metabolism
Research Programs Unit
Faculty of Medicine
University of Helsinki
HUS Abdominal Center
Endokrinologian yksikkö
Helsinki University Hospital Area
HUS Internal Medicine and Rehabilitation
INDIVIDRUG - Individualized Drug Therapy
HUS Medical Imaging Center
Department of Diagnostics and Therapeutics
Date: 2021-05
Language: eng
Number of pages: 11
Belongs to series: Diabetes, obesity and metabolism
ISSN: 1462-8902
DOI: https://doi.org/10.1111/dom.14328
URI: http://hdl.handle.net/10138/340318
Abstract: Aim: To elucidate the impact of liraglutide on the kinetics of apolipoprotein (apo) B48- and apoB100-containing triglyceride-rich lipoproteins in subjects with type 2 diabetes (T2D) after a single fat-rich meal. Materials and Methods: Subjects with T2D were included in a study to investigate postprandial apoB48 and apoB100 metabolism before and after 16 weeks on 1.8 mg/day liraglutide (n = 14) or placebo (n = 4). Stable isotope tracer and compartmental modelling techniques were used to determine the impact of liraglutide on chylomicron and very low-density lipoprotein (VLDL) production and clearance after a single fat-rich meal. Results: Liraglutide reduced apoB48 synthesis in chylomicrons by 60% (p <.0001) and increased the triglyceride/apoB48 ratio (i.e. the size) of chylomicrons (p <.001). Direct clearance of chylomicrons, a quantitatively significant pathway pretreatment, decreased by 90% on liraglutide (p <.001). Liraglutide also reduced VLDL1-triglyceride secretion (p = .017) in parallel with reduced liver fat. Chylomicron-apoB48 production and particle size were related to insulin sensitivity (p = .015 and p <.001, respectively), but these associations were perturbed by liraglutide. Conclusions: In a physiologically relevant setting that mirrored regular feeding in subjects with T2D, liraglutide promoted potentially beneficial changes on postprandial apoB48 metabolism. Using our data in an integrated metabolic model, we describe how the action of liraglutide in T2D on chylomicron and VLDL kinetics could lead to decreased generation of remnant lipoproteins.
Subject: dyslipidaemia
GLP-1 analogue
type 2 diabetes
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: acceptedVersion


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