Diabetes Mellitus and Atrial Remodeling: Mechanisms and Potential Upstream Therapies

Abstract

Summary Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, and its prevalence has increasing substantially over the last decades. Recent data suggest that there is an increased risk of AF among the patients with diabetes mellitus (DM). However, the potential molecular mechanisms regarding DM‐related AF and diabetic atrial remodeling are not fully understood. In this comprehensive review, we would like to summarize the potential relationship between diabetes and atrial remodeling, including structural, electrical, and autonomic remodeling. Also, some upstream therapies, such as thiazolidinediones, probucol, ACEI/ARBs, may play an important role in the prevention and treatment of AF. Therefore, large prospective randomized, controlled trials and further experimental studies should be challengingly continued.

Type 2 diabetes mellitus and atrial fibrillation: From mechanisms to clinical practice

“…All of these metabolic changes lead to endothelial dysfunction, abnormal activation of the reninangiotensin-aldosterone system (RAAS) and acceleration of atherogenesis, which could be responsible for AF occurrence [2,[7][8][9]. Diabetes could also cause structural, electrical, electromechanical and autonomic remodelling [10].…”

“…Atrial fibrosis could be caused by inflammation (oxidative stress), increased production of advanced glycation end products, increased expression of transforming growth factor-␤ and expression changes of gap junction proteins [10].…”

“…The principal characters of atrial electrical remodelling involve atrial effective refractory period shortening and its dispersion, as well as impairment of its frequency adaptation and consequent inter-atrial conduction delay [10]. Changes in left atrial diameter, atrial activation time and voltage in patients with diabetes have been associated with atrial structural remodelling, not only electrical, especially in patients with AF.…”

Diabetes mellitus and atrial fibrillation: Pathophysiological mechanisms and potential upstream therapies

“…Experimental studies have demonstrated that TZDs prevent atrial electrical and structural remodeling through their antiinflammatory and antioxidant properties [75][76][77][78][79]. The possible targets of PPAR-c agonists include transforming growth factor-b (TGF-b), tumor necrosis factor-a (TNF-a), atrial natriuretic peptide (ANP), superoxide dismutase (SOD), malondialdehyde (MDA), NADPH oxidase subunits, and voltage-dependent Ca 2+ currents [80]. In the clinical setting, anecdotal evidence indicated a remarkable improvement of paroxysmal atrial fibrillation (AF) in 2 diabetic patients after treatment with rosiglitazone [81].…”

Xanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits

“…Although the pathophysiological mechanisms linking diabetes mellitus (DM) to AF development have not been completely elucidated. Autonomic, electrical and structural remodeling involving activation of proinflammatory pathways, abnormalities of calcium (Ca 2+ ) homeostasis, as well as oxidative stress‐mediated damage play important roles 3, 4, 5, 6…”