Preman Kumarathurai1, Ahmad Sajadieh2, Christian Anholm3,4, Ole P Kristiansen2, Steen B Haugaard3,5, Olav W Nielsen2. 1. Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Bispebjerg Bakke 23, 2400, Copenhagen, Denmark. preman.kumarathurai@dadlnet.dk. 2. Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Bispebjerg Bakke 23, 2400, Copenhagen, Denmark. 3. Department of Internal Medicine, University Hospital of Amager, Copenhagen, Denmark. 4. Department of Nephrology and Endocrinolgy, University Hospital of Hillerød, Hillerød, Denmark. 5. Department of Endocrinology, University Hospital of Bispebjerg, Copenhagen, Denmark.
Abstract
BACKGROUND:Diastolic dysfunction is highly prevalent in patients with type 2 diabetes mellitus (T2DM) and is associated with overweight, glucose dysregulation and coronary artery disease (CAD). The GLP-1 receptor agonist, liraglutide, has shown to induce weight loss and improve metabolic factors, thus modulating factors associated with diastolic dysfunction. We have previously reported the effects of liraglutide on systolic function, and in this current study we explore the effects of liraglutide on diastolic function parameters in patients with stable CAD, preserved left ventricular ejection fraction (LVEF), and newly diagnosed T2DM. METHODS:Thirty subjects were randomized to liraglutide or placebo intervention for 12 + 12-weeks in this double-blind cross-over study. 2D-echocardiography using tissue velocity imaging was used for assessment of diastolic function parameters. Early diastolic filling velocity (E), late atrial filling velocity (A), E-wave deceleration time (EDT) and E/A ratio was assessed from the pulse wave (PW)-Doppler velocity recording of the mitral inflow. Peak early diastolic annular velocities (e') was measured from color tissue doppler images. RESULTS:Liraglutide, when compared to placebo, induced a significant reduction in average e' and lateral e' velocities (- 0.57 cm/s [- 1.05 to - 0.08] and -0.74 cm/s [-1.32 to -0.15], respectively). Adjusted for the concomitant increase in HR (+ 6.16 bpm [0.79 to 11.54], the changes were not significant. No significant changes in other diastolic function parameters were observed. CONCLUSIONS:Liraglutide therapy did not improve any diastolic function parameters in subjects with T2DM, CAD, and preserved LVEF. Instead, a deterioration in e' was observed, which was associated to an increase in heart rate induced by liraglutide therapy. Trial registration Clinical Trial Registration: http://www.clinicaltrials.gov (unique identifier: NCT01595789) (first submitted May 8, 2012).
RCT Entities:
BACKGROUND:Diastolic dysfunction is highly prevalent in patients with type 2 diabetes mellitus (T2DM) and is associated with overweight, glucose dysregulation and coronary artery disease (CAD). The GLP-1 receptor agonist, liraglutide, has shown to induce weight loss and improve metabolic factors, thus modulating factors associated with diastolic dysfunction. We have previously reported the effects of liraglutide on systolic function, and in this current study we explore the effects of liraglutide on diastolic function parameters in patients with stable CAD, preserved left ventricular ejection fraction (LVEF), and newly diagnosed T2DM. METHODS: Thirty subjects were randomized to liraglutide or placebo intervention for 12 + 12-weeks in this double-blind cross-over study. 2D-echocardiography using tissue velocity imaging was used for assessment of diastolic function parameters. Early diastolic filling velocity (E), late atrial filling velocity (A), E-wave deceleration time (EDT) and E/A ratio was assessed from the pulse wave (PW)-Doppler velocity recording of the mitral inflow. Peak early diastolic annular velocities (e') was measured from color tissue doppler images. RESULTS: Liraglutide, when compared to placebo, induced a significant reduction in average e' and lateral e' velocities (- 0.57 cm/s [- 1.05 to - 0.08] and -0.74 cm/s [-1.32 to -0.15], respectively). Adjusted for the concomitant increase in HR (+ 6.16 bpm [0.79 to 11.54], the changes were not significant. No significant changes in other diastolic function parameters were observed. CONCLUSIONS: Liraglutide therapy did not improve any diastolic function parameters in subjects with T2DM, CAD, and preserved LVEF. Instead, a deterioration in e' was observed, which was associated to an increase in heart rate induced by liraglutide therapy. Trial registration Clinical Trial Registration: http://www.clinicaltrials.gov (unique identifier: NCT01595789) (first submitted May 8, 2012).
Authors: Sherif F Nagueh; Otto A Smiseth; Christopher P Appleton; Benjamin F Byrd; Hisham Dokainish; Thor Edvardsen; Frank A Flachskampf; Thierry C Gillebert; Allan L Klein; Patrizio Lancellotti; Paolo Marino; Jae K Oh; Bogdan Alexandru Popescu; Alan D Waggoner Journal: J Am Soc Echocardiogr Date: 2016-04 Impact factor: 5.251
Authors: Kenneth B Margulies; Adrian F Hernandez; Margaret M Redfield; Michael M Givertz; Guilherme H Oliveira; Robert Cole; Douglas L Mann; David J Whellan; Michael S Kiernan; G Michael Felker; Steven E McNulty; Kevin J Anstrom; Monica R Shah; Eugene Braunwald; Thomas P Cappola Journal: JAMA Date: 2016-08-02 Impact factor: 56.272
Authors: Rebecca L Scalzo; Kerrie L Moreau; Cemal Ozemek; Leah Herlache; Shawna McMillin; Sarah Gilligan; Amy G Huebschmann; Tim A Bauer; Jennifer Dorosz; Jane E B Reusch; Judith G Regensteiner Journal: J Diabetes Complications Date: 2016-10-07 Impact factor: 2.852
Authors: Thomas Nyström; Irene Santos-Pardo; Fredric Hedberg; Johan Wardell; Nils Witt; Yang Cao; Leif Bojö; Bo Nilsson; Johan Jendle Journal: Front Endocrinol (Lausanne) Date: 2017-11-14 Impact factor: 5.555
Authors: Maurice B Bizino; Ingrid M Jazet; Jos J M Westenberg; Huub J van Eyk; Elisabeth H M Paiman; Jan W A Smit; Hildebrandus J Lamb Journal: Cardiovasc Diabetol Date: 2019-04-30 Impact factor: 9.951
Authors: Steven P Marso; Gilbert H Daniels; Kirstine Brown-Frandsen; Peter Kristensen; Johannes F E Mann; Michael A Nauck; Steven E Nissen; Stuart Pocock; Neil R Poulter; Lasse S Ravn; William M Steinberg; Mette Stockner; Bernard Zinman; Richard M Bergenstal; John B Buse Journal: N Engl J Med Date: 2016-06-13 Impact factor: 176.079
Authors: Preman Kumarathurai; Christian Anholm; Olav W Nielsen; Ole P Kristiansen; Jens Mølvig; Sten Madsbad; Steen B Haugaard; Ahmad Sajadieh Journal: Cardiovasc Diabetol Date: 2016-07-26 Impact factor: 9.951
Authors: Shi Yin Wong; Ainsley Ryan Yan Bin Lee; Aaron Hon Jiun Sia; Yu Jun Wo; Yao Hao Teo; Yao Neng Teo; Nicholas L Syn; Ching-Ching Ong; Lynette L Teo; Tiong-Cheng Yeo; Kian-Keong Poh; William K Kong; Raymond C Wong; Ching-Hui Sia Journal: Cardiovasc Drugs Ther Date: 2022-07-12 Impact factor: 3.947