Department of Endocrinology and Metabolism, Research Centre for Diabetes and Metabolism, West China Hospital, Sichuan University, Chengdu, China.
Signal Transduct Target Ther. 2024 Oct 2;9(1):262. doi: 10.1038/s41392-024-01951-9.
Type 2 diabetes (T2D) is a disease characterized by heterogeneously progressive loss of islet β cell insulin secretion usually occurring after the presence of insulin resistance (IR) and it is one component of metabolic syndrome (MS), and we named it metabolic dysfunction syndrome (MDS). The pathogenesis of T2D is not fully understood, with IR and β cell dysfunction playing central roles in its pathophysiology. Dyslipidemia, hyperglycemia, along with other metabolic disorders, results in IR and/or islet β cell dysfunction via some shared pathways, such as inflammation, endoplasmic reticulum stress (ERS), oxidative stress, and ectopic lipid deposition. There is currently no cure for T2D, but it can be prevented or in remission by lifestyle intervention and/or some medication. If prevention fails, holistic and personalized management should be taken as soon as possible through timely detection and diagnosis, considering target organ protection, comorbidities, treatment goals, and other factors in reality. T2D is often accompanied by other components of MDS, such as preobesity/obesity, metabolic dysfunction associated steatotic liver disease, dyslipidemia, which usually occurs before it, and they are considered as the upstream diseases of T2D. It is more appropriate to call "diabetic complications" as "MDS-related target organ damage (TOD)", since their development involves not only hyperglycemia but also other metabolic disorders of MDS, promoting an up-to-date management philosophy. In this review, we aim to summarize the underlying mechanism, screening, diagnosis, prevention, and treatment of T2D, especially regarding the personalized selection of hypoglycemic agents and holistic management based on the concept of "MDS-related TOD".
2 型糖尿病(T2D)是一种以胰岛β细胞胰岛素分泌进行性丧失为特征的疾病,通常发生在胰岛素抵抗(IR)之后,是代谢综合征(MS)的一个组成部分,我们将其命名为代谢功能障碍综合征(MDS)。T2D 的发病机制尚未完全阐明,IR 和β细胞功能障碍在其病理生理学中起着核心作用。血脂异常、高血糖以及其他代谢紊乱通过一些共同的途径导致 IR 和/或胰岛β细胞功能障碍,如炎症、内质网应激(ERS)、氧化应激和异位脂质沉积。目前尚无治愈 T2D 的方法,但通过生活方式干预和/或某些药物可以预防或缓解。如果预防失败,应尽快通过及时检测和诊断,考虑目标器官保护、合并症、治疗目标和其他现实因素,采取全面和个性化的管理。T2D 常伴有 MDS 的其他成分,如前肥胖/肥胖、与代谢功能障碍相关的脂肪性肝病、血脂异常,这些通常发生在 T2D 之前,被认为是 T2D 的上游疾病。将“糖尿病并发症”称为“MDS 相关靶器官损伤(TOD)”更为恰当,因为它们的发展不仅涉及高血糖,还涉及 MDS 的其他代谢紊乱,促进了最新的管理理念。在这篇综述中,我们旨在总结 T2D 的潜在机制、筛查、诊断、预防和治疗,特别是基于“MDS 相关 TOD”概念的降糖药物个性化选择和整体管理。