Effect of antidiabetic drugs on the risk of atrial fibrillation: mechanistic insights from clinical evidence and transla
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Cellular and Molecular Life Sciences
REVIEW
Effect of antidiabetic drugs on the risk of atrial fibrillation: mechanistic insights from clinical evidence and translational studies Ting‑Wei Lee1,2 · Ting‑I. Lee1,2,3 · Yung‑Kuo Lin4,5 · Yao‑Chang Chen6 · Yu‑Hsun Kao7,8 · Yi‑Jen Chen7,9,10 Received: 25 April 2020 / Revised: 18 August 2020 / Accepted: 12 September 2020 © Springer Nature Switzerland AG 2020
Abstract Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF), which is the most common sustained arrhythmia and is associated with substantial morbidity and mortality. Advanced glycation end product and its receptor activation, cardiac energy dysmetabolism, structural and electrical remodeling, and autonomic dysfunction are implicated in AF pathophysiology in diabetic hearts. Antidiabetic drugs have been demonstrated to possess therapeutic potential for AF. However, clinical investigations of AF in patients with DM have been scant and inconclusive. This article provides a comprehensive review of research findings on the association between DM and AF and critically analyzes the effect of different pharmacological classes of antidiabetic drugs on AF. Keywords DPP-4 · GLP-1 · Metformin · SGLT2 · Thiazolidinedione
Introduction Diabetes mellitus (DM) is a complex chronic disease, and its prevalence continues to increase worldwide [1]: it was 6.4% among adults in 2010, and this rate is expected to increase to 7.7% by 2030 [2]. Accumulating evidence suggests that DM is an independent risk factor for atrial fibrillation (AF), which is the most common sustained arrhythmia [3, 4]. AF not only causes heart failure and stroke, but also increases the risk of myocardial infarction. Clinical studies showed that AF doubles the risk of myocardial infarction [5, 6]. Therefore, AF has a critical impact on human
* Yi‑Jen Chen [email protected] 1
Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
2
3
4
Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
health and socioeconomic burden. The Framingham Heart Study comprising 4731 participants demonstrated that DM significantly increased the risk of AF during up to 38 years of follow-up [3]. The Women’s Health Initiative Observational Study involving 81,892 postmenopausal women reported that patients with DM had a 55% increased risk of AF over an average follow-up period of 9.8 years [7]. A meta-analysis of 29 studies that included 8,037,756 individuals reported that DM was associated with a 49% increase in the development of AF [8]. This analysis also showed that women with DM were 24% more likely
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