Liraglutide Improves Myocardial Perfusion and Energetics and Exercise Tolerance in Patients With Type 2 Diabetes.

Autor:	Chowdhary A; University of Leeds, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, United Kingdom., Thirunavukarasu S; University of Leeds, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, United Kingdom., Joseph T; University of Leeds, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, United Kingdom., Jex N; University of Leeds, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, United Kingdom., Kotha S; University of Leeds, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, United Kingdom., Giannoudi M; University of Leeds, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, United Kingdom., Procter H; University of Leeds, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, United Kingdom., Cash L; University of Leeds, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, United Kingdom., Akkaya S; University of Leeds, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, United Kingdom., Broadbent D; University of Leeds, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, United Kingdom., Xue H; National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA., Swoboda P; University of Leeds, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, United Kingdom., Valkovič L; Centre for Clinical Magnetic Resonance Research (OCMR), RDM Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom; Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia., Kellman P; National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA., Plein S; University of Leeds, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, United Kingdom., Rider OJ; Centre for Clinical Magnetic Resonance Research (OCMR), RDM Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom., Neubauer S; Centre for Clinical Magnetic Resonance Research (OCMR), RDM Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom., Greenwood JP; Baker Heart and Diabetes Institute, Melbourne, Australia; Monash University, Melbourne, Australia; University of Melbourne, Melbourne, Australia., Levelt E; University of Leeds, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, United Kingdom; Baker Heart and Diabetes Institute, Melbourne, Australia. Electronic address: e.levelt@leeds.ac.uk.
Jazyk:	angličtina
Zdroj:	Journal of the American College of Cardiology [J Am Coll Cardiol] 2024 Aug 06; Vol. 84 (6), pp. 540-557.
DOI:	10.1016/j.jacc.2024.04.064
Abstrakt:	Background: Type 2 diabetes (T2D) is characterized by insulin resistance (IR) and dysregulated insulin secretion. Glucagon-like peptide-1 receptor agonist liraglutide promotes insulin secretion, whereas thiazolidinedione-pioglitazone decreases IR. Objectives: This study aimed to compare the efficacies of increasing insulin secretion vs decreasing IR strategies for improving myocardial perfusion, energetics, and function in T2D via an open-label randomized crossover trial. Methods: Forty-one patients with T2D (age 63 years [95% CI: 59-68 years], 27 [66%] male, body mass index 27.8 kg/m 2 ) [95% CI: 26.1-29.5 kg/m 2 )]) without cardiovascular disease were randomized to liraglutide or pioglitazone for a 16-week treatment followed by an 8-week washout and a further 16-week treatment with the second trial drug. Participants underwent rest and dobutamine stress 31 phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance for measuring the myocardial energetics index phosphocreatine to adenosine triphosphate ratio, myocardial perfusion (rest, dobutamine stress myocardial blood flow, and myocardial perfusion reserve), left ventricular (LV) volumes, systolic and diastolic function (mitral in-flow E/A ratio), before and after treatment. The 6-minute walk-test was used for functional assessments. Results: Pioglitazone treatment resulted in significant increases in LV mass (96 g [95% CI: 68-105 g] to 105 g [95% CI: 74-115 g]; P = 0.003) and mitral-inflow E/A ratio (1.04 [95% CI: 0.62-1.21] to 1.34 [95% CI: 0.70-1.54]; P = 0.008), and a significant reduction in LV concentricity index (0.79 mg/mL [95% CI: 0.61-0.85 mg/mL] to 0.73 mg/mL [95% CI: 0.56-0.79 mg/mL]; P = 0.04). Liraglutide treatment increased stress myocardial blood flow (1.62 mL/g/min [95% CI: 1.19-1.75 mL/g/min] to 2.08 mL/g/min [95% CI: 1.57-2.24 mL/g/min]; P = 0.01) and myocardial perfusion reserve (2.40 [95% CI: 1.55-2.68] to 2.90 [95% CI: 1.83-3.18]; P = 0.01). Liraglutide treatment also significantly increased the rest (1.47 [95% CI: 1.17-1.58] to 1.94 [95% CI: 1.52-2.08]; P =0.00002) and stress phosphocreatine to adenosine triphosphate ratio (1.32 [95% CI: 1.05-1.42] to 1.58 [95% CI: 1.19-1.71]; P = 0.004) and 6-minute walk distance (488 m [95% CI: 458-518 m] to 521 m [95% CI: 481-561 m]; P = 0.009). Conclusions: Liraglutide treatment resulted in improved myocardial perfusion, energetics, and 6-minute walk distance in patients with T2D, whereas pioglitazone showed no effect on these parameters (Lean-DM [Targeting Beta-cell Failure in Lean Patients With Type 2 Diabetes]; NCT04657939). Competing Interests: Funding Support and Author Disclosures The views expressed are those of the author(s) and not necessarily those of the Wellcome Trust, the NHS, the NIHR, or the Department of Health and Social Care. This independent research has been jointly funded by the Wellcome Trust (grant number: 221690/Z/20/Z) and Diabetes UK (grant number:18/0005870) and has been performed at the National Institute for Health and Care Research (NIHR) Leeds Biomedical Research Centre (BRC) (NIHR203331). Funding for open access charge is from Wellcome Trust (grant number: 221690/Z/20/Z). Dr Chowdhary has received grants from the British Heart Foundation (grant number: FS/CRTF/20/24003). Dr Valkovič has received grants from the Sir Henry Dale Fellowship supported jointly by the Wellcome Trust and the Royal Society (#221805/Z/20/Z), and Slovak Grant Agencies VEGA (#2/0004/23) and APVV (#21-0299). Dr Levelt acknowledges support from the Wellcome Trust Clinical Career Development Fellowship (grant number: 221690/Z/20/Z), Diabetes UK (grant number: UK 18/0005908) and the NIHR Leeds Biomedical Research Centre. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu