Humanitas Clinical and Research Center IRCCS, Milan, Italy; National and Kapodistrian University of Athens, Athens, Greece.
National and Kapodistrian University of Athens, Athens, Greece.
Diabetes Res Clin Pract. 2021 Apr;174:108724. doi: 10.1016/j.diabres.2021.108724. Epub 2021 Feb 27.
Atrial fibrillation (AF) and diabetes mellitus (DM) are commonly encountered in clinical practice. Although, the long term macrovascular and microvascular sequela of DM are well validated, the association between the less prevalent type 1 DM (T1DM) and atrial arrhythmogenesis is poorly understood. In the present review we highlight the current experimental and clinical data addressing this complex interaction. Animal studies support that T1DM, characterized by insulin deficiency and glycemic variability, impairs phosphatidylinositol 3‑kinase (PI3K)/protein kinase B signaling pathway. This pathway holds a central role in atrial electrical and structural remodeling responsible for arrhythmia initiation and maintenance. The molecular ''footprint'' of T1DM in atrial myocytes seems to involve a state of increased oxidative stress, impaired glucose transportation, ionic channel dysregulation and eventually fibrosis. On the contrary only a few clinical studies have examined the role of T1DM as an independent risk factor for AF development, and are discussed here. Further research is needed to solidify the real magnitude of this association and to investigate the clinical implications of PI3K molecular signaling pathway in atrial fibrillation management.
心房颤动(AF)和糖尿病(DM)在临床实践中很常见。尽管糖尿病的长期大血管和微血管后遗症已得到充分证实,但人们对不太常见的 1 型糖尿病(T1DM)与心房心律失常发生之间的关系了解甚少。在本综述中,我们重点介绍了目前针对这一复杂相互作用的实验和临床数据。动物研究支持 T1DM 表现为胰岛素缺乏和血糖变异性,会损害磷脂酰肌醇 3-激酶(PI3K)/蛋白激酶 B 信号通路。该通路在心房电和结构重构中起核心作用,负责心律失常的发生和维持。T1DM 在心房肌细胞中的分子“足迹”似乎涉及氧化应激增加、葡萄糖转运受损、离子通道失调,最终导致纤维化的状态。相反,只有少数临床研究探讨了 T1DM 作为 AF 发展的独立危险因素的作用,本文对这些研究进行了讨论。需要进一步的研究来确定这种关联的真实程度,并研究 PI3K 分子信号通路在心房颤动管理中的临床意义。