Kovler Diabetes Center and the Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Department of Endocrinology, Edward Hines Junior VA Hospital, Hines, IL 60141, USA.
Int J Mol Sci. 2021 Feb 21;22(4):2151. doi: 10.3390/ijms22042151.
Type 2 diabetes (T2D) typically occurs in the setting of obesity and insulin resistance, where hyperglycemia is associated with decreased pancreatic β-cell mass and function. Loss of β-cell mass has variably been attributed to β-cell dedifferentiation and/or death. In recent years, it has been proposed that circulating epigenetically modified DNA fragments arising from β cells might be able to report on the potential occurrence of β-cell death in diabetes. Here, we review published literature of DNA-based β-cell death biomarkers that have been evaluated in human cohorts of islet transplantation, type 1 diabetes, and obesity and type 2 diabetes. In addition, we provide new data on the applicability of one of these biomarkers (cell free unmethylated DNA) in adult cohorts across a spectrum from obesity to T2D, in which no significant differences were observed, and compare these findings to those previously published in youth cohorts where differences were observed. Our analysis of the literature and our own data suggest that β-cell death may occur in subsets of individuals with obesity and T2D, however a more sensitive method or refined study designs are needed to provide better alignment of sampling with disease progression events.
2 型糖尿病（T2D）通常发生在肥胖和胰岛素抵抗的情况下，此时高血糖与胰腺β细胞数量和功能减少有关。β细胞数量的减少归因于β细胞去分化和/或死亡。近年来，有人提出，来自β细胞的循环表观遗传修饰的 DNA 片段可能能够报告糖尿病中β细胞死亡的潜在发生。在这里，我们回顾了已在胰岛移植、1 型糖尿病和肥胖及 2 型糖尿病的人类队列中进行评估的基于 DNA 的β细胞死亡生物标志物的已发表文献。此外，我们提供了关于其中一种生物标志物（无甲基化游离 DNA）在肥胖到 T2D 一系列成人队列中的适用性的新数据，在这些队列中未观察到显著差异，并将这些发现与以前在青年队列中观察到的差异进行了比较。我们对文献的分析和我们自己的数据表明，β细胞死亡可能发生在肥胖和 T2D 个体的亚组中，然而需要更敏感的方法或改进的研究设计，以便更好地将采样与疾病进展事件对齐。
