In vivo biomarkers for detection of β cell death

Abstract

There is an immediate need for a noninvasive approach to detect β cell destruction during the initial stages of type I diabetes and late stages of type II diabetes in order to permit early preventative and interventional treatment strategies. The appearance of circulating biomarkers has been highly useful in diagnosing specific organ damage and early detection of some types of cancer. Hence, for nearly two decades, there have been efforts to identify analogous prognosticating factors in diabetes. To date, studies have identified several β cell-selective proteins which have recently been validated as biomarkers for detection of acute islet insulin cell death in vivo: glutamic acid decarboxylase 65 (GAD65), doublecortin (DCX), and protein phosphatase inhibitor 1 (PPP1R1A). More recently, the PCR detection of circulating genomic DNA originating from the β cell by its methylation fingerprint, as well as circulating β cell-specific microRNA, has offered more sensitive means to discern in vivo islet damage. This chapter surveys the current state of β cell biomarkers for real-time detection of cell death in vivo. While preclinical data suggests that we still have a long way to go, the successful translation of the biomarker approach to humans will revolutionize the way in which diabetes is treated.