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

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Volume Title

A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Date

2021-05

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en

Pages

11
1191-1201

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Diabetes, Obesity and Metabolism, Volume 23, issue 5

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 l.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.

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Publisher Copyright: © 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

dyslipidaemia, GLP-1 analogue, type 2 diabetes

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Citation

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 & Borén, 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