Lorenzo-Almorós Ana, Casado Cerrada Jesús, Álvarez-Sala Walther Luis-Antonio, Méndez Bailón Manuel, Lorenzo González Óscar
Internal Medicine Department, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain.
Department of Medicine, School of Medicine, Universidad Complutense de Madrid, 28007 Madrid, Spain.
J Clin Med. 2023 Apr 14;12(8):2868. doi: 10.3390/jcm12082868.
Atrial fibrillation (AF) is the most common arrhythmia in adults and diabetes mellitus (DM) is a major risk factor for cardiovascular diseases. However, the relationship between both pathologies has not been fully documented and new evidence supports the existence of direct and independent links. In the myocardium, a combination of structural, electrical, and autonomic remodeling may lead to AF. Importantly, patients with AF and DM showed more dramatic alterations than those with AF or DM alone, particularly in mitochondrial respiration and atrial remodeling, which alters conductivity, thrombogenesis, and contractile function. In AF and DM, elevations of cytosolic Ca⁺ and accumulation of extra cellular matrix (ECM) proteins at the interstitium can promote delayed afterdepolarizations. The DM-associated low-grade inflammation and deposition/infiltration of epicardial adipose tissue (EAT) enforce abnormalities in Ca handling and in excitation-contraction coupling, leading to atrial myopathy. This atrial enlargement and the reduction in passive emptying volume and fraction can be key for AF maintenance and re-entry. Moreover, the stored EAT can prolong action of potential durations and progression from paroxysmal to persistent AF. In this way, DM may increase the risk of thrombogenesis as a consequence of increased glycation and oxidation of fibrinogen and plasminogen, impairing plasmin conversion and resistance to fibrinolysis. Additionally, the DM-associated autonomic remodeling may also initiate AF and its re-entry. Finally, further evidence of DM influence on AF development and maintenance are based on the anti-arrhythmogenic effects of certain anti-diabetic drugs like SGLT2 inhibitors. Therefore, AF and DM may share molecular alterations related to Ca mobility, mitochondrial function and ECM composition that induce atrial remodeling and defects in autonomic stimulation and conductivity. Likely, some specific therapies could work against the associated cardiac damage to AF and/or DM.
心房颤动（AF）是成年人中最常见的心律失常，而糖尿病（DM）是心血管疾病的主要危险因素。然而，这两种病症之间的关系尚未得到充分记录，新证据支持存在直接且独立的联系。在心肌中，结构、电和自主神经重塑的组合可能导致房颤。重要的是，患有房颤和糖尿病的患者比单独患有房颤或糖尿病的患者表现出更显著的改变，特别是在线粒体呼吸和心房重塑方面，这会改变传导性、血栓形成和收缩功能。在房颤和糖尿病中，胞质Ca⁺升高和细胞外基质（ECM）蛋白在间质中的积累可促进延迟后去极化。与糖尿病相关的低度炎症以及心外膜脂肪组织（EAT）的沉积/浸润会加剧钙处理和兴奋 - 收缩偶联异常，导致心房肌病。这种心房扩大以及被动排空体积和分数的降低可能是房颤维持和折返的关键。此外，储存的EAT可延长动作电位持续时间，并促使房颤从阵发性发展为持续性。这样，糖尿病可能由于纤维蛋白原和纤溶酶原糖基化和氧化增加而增加血栓形成风险，损害纤溶酶转化和纤维蛋白溶解抵抗。此外，与糖尿病相关的自主神经重塑也可能引发房颤及其折返。最后，糖尿病对房颤发生和维持影响的进一步证据基于某些抗糖尿病药物（如SGLT2抑制剂）的抗心律失常作用。因此，房颤和糖尿病可能共享与钙流动性、线粒体功能和ECM组成相关的分子改变，这些改变会诱导心房重塑以及自主神经刺激和传导性缺陷。可能有一些特定疗法可以对抗与房颤和/或糖尿病相关的心脏损伤。
