Table_1_Heterogeneity of Metabolic Defects in Type 2 Diabetes and Its Relation to Reactive Oxygen Species and Alterations in Beta-Cell Mass.xlsx

Type 2 diabetes (T2D) is a complex and heterogeneous disease which affects millions of people worldwide. The classification of diabetes is at an interesting turning point and there have been several recent reports on sub-classification of T2D based on phenotypical and metabolic characteristics. An important, and perhaps so far underestimated, factor in the pathophysiology of T2D is the role of oxidative stress and reactive oxygen species (ROS). There are multiple pathways for excessive ROS formation in T2D and in addition, beta-cells have an inherent deficit in the capacity to cope with oxidative stress. ROS formation could be causal, but also contribute to a large number of the metabolic defects in T2D, including beta-cell dysfunction and loss. Currently, our knowledge on beta-cell mass is limited to autopsy studies and based on comparisons with healthy controls. The combined evidence suggests that beta-cell mass is unaltered at onset of T2D but that it declines progressively. In order to better understand the pathophysiology of T2D, to identify and evaluate novel treatments, there is a need for in vivo techniques able to quantify beta-cell mass. Positron emission tomography holds great potential for this purpose and can in addition map metabolic defects, including ROS activity, in specific tissue compartments. In this review, we highlight the different phenotypical features of T2D and how metabolic defects impact oxidative stress and ROS formation. In addition, we review the literature on alterations of beta-cell mass in T2D and discuss potential techniques to assess beta-cell mass and metabolic defects in vivo.

2型糖尿病（T2D）是一种复杂且异质性的疾病，全球范围内影响数以百万计的人。糖尿病的分类正处于一个有趣的转折点，近年来已有关于基于表型和代谢特征的T2D亚型分类的若干报道。在T2D的病理生理学中，氧化应激和活性氧（ROS）的作用是一个重要且可能迄今为止尚未充分估计的因素。T2D中存在多种过量的ROS形成的途径，此外，β细胞在应对氧化应激方面的能力存在固有的不足。ROS的形成可能是病因性的，但同时也可能对T2D中大量代谢缺陷的产生和加剧起到贡献作用，包括β细胞功能障碍和丢失。目前，我们对β细胞质量的了解仅限于尸检研究，并基于与健康对照者的比较。综合证据表明，β细胞质量在T2D发病初期并未改变，但随后逐渐下降。为了更好地理解T2D的病理生理学，识别和评估新型治疗方法，迫切需要能够量化β细胞质量的体内技术。正电子发射断层扫描（PET）在此目的上具有巨大的潜力，并且还能映射特定组织间隔内的代谢缺陷，包括ROS活性。在本综述中，我们强调了T2D的不同表型特征以及代谢缺陷如何影响氧化应激和ROS的形成。此外，我们还回顾了T2D中β细胞质量变化的相关文献，并讨论了评估β细胞质量及代谢缺陷的体内技术的潜在方法。