Cell-free dna fragments as biomarkers of islet β-cell death in obesity and type 2 diabetes

Abstract

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 INS DNA) in adult cohorts across a spectrum from obesity to T2D, in which no significant differences were observed, and com-pare these findings to those previously published in youth cohorts where differences were ob-served. Our analysis of the literature and our own data suggest that β-cell death may occur in sub-sets 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.