Association of metformin with lower atrial fibrillation risk among patients with type 2 diabetes mellitus: a population-based dynamic cohort and in vitro studies

Cardiovascular Diabetology

Original Investigation

Ming-Shien Wen¹  Yung-Hsin Yeh¹  Shang-Hung Chang¹  Wei-Jan Chen¹  Lung-Sheng Wu¹  Meng-Jiun Chiou²  Jia-Rou Liu²  Lai-Chu See³  Kuang-Hui Yu⁴  Chang-Fu Kuo⁴ 

[1] Chang Gung University and Department of Cardiology, Chang Gung Memorial Hospital, Kweishan 333, Taoyuan, Taiwan;Department of Public Health, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan 333, Taoyuan, Taiwan;Department of Public Health, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan 333, Taoyuan, Taiwan;Biostatistics Core Laboratory, Molecular Medicine Research Center, Chang Gung University, Kweishan 333, Taiwan;Department of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Kweishan 333, Taiwan;

关键词: Metformin;    Atrial fibrillation;    Myolysis;    Oxidative stress;    Diabetes mellitus;   

DOI  :  10.1186/s12933-014-0123-x

 received in 2014-05-10, accepted in 2014-08-04,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundAtrial fibrillation (AF), an inflammatory process involving arrhythmia, is associated with severe morbidity and mortality and commonly seen in patients with diabetes mellitus (DM). The effect of metformin, the most commonly used medication for patients with DM, on AF has not been investigated. The primary aim of this study was to examine whether metformin prevented the occurrence of AF in type 2 DM patients by analyzing a nationwide, population-based dynamic cohort. Additionally, we investigated the effect of metformin on tachycardia-induced myolysis and oxidative stress in atrial cells.MethodsThe study population included 645,710 patients with type 2 diabetes and not using other anti-diabetic medication from a subset of the Taiwan National Health Insurance Research Database. Of these patients, those who used metformin were categorized as the user group, and the remaining were classified as the non-user group. The time-dependent Cox’s proportional hazard model was used to examine the effect of metformin on AF and the status of metformin use was treated as a time-dependent covariate. HL-1 atrial cells were paced with or without metformin, and then troponin and heavy-chain-myosin were measured as markers of myolysis.ResultsAfter 13 years of follow-up, 9,983 patients developed AF with an incidence rate of 1.5% (287 per 100,000 person-years). After adjusting for co-morbidities and medications, metformin independently protected the diabetic patients from new-onset AF with a hazard ratio of .81 (95% confidence interval 0.76-0.86, p < 0.0001). Metformin significantly decreased the extent of pacing-induced myolysis and the production of reactive oxygen species.ConclusionMetformin use was associated with a decreased risk of AF in patients with type 2 DM who were not using other anti-diabetic medication, probably via attenuation of atrial cell tachycardia-induced myolysis and oxidative stress.

【 授权许可】

Unknown   
© Chang et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.