Biomarkers of islet beta cell stress and death in type 1 diabetes

Abstract

Recent work on the pathogenesis of type 1 diabetes has led to an evolving recognition of the heterogeneity of this disease, both with regards to clinical phenotype and responses to therapies to prevent or revert diabetes. This heterogeneity not only limits efforts to accurately predict clinical disease but also is reflected in differing responses to immunomodulatory therapeutics. Thus, there is a need for robust biomarkers of beta cell health, which could provide insight into pathophysiological differences in disease course, improve disease prediction, increase the understanding of therapeutic responses to immunomodulatory interventions and identify individuals most likely to benefit from these therapies. In this review, we outline current literature, limitations and future directions for promising circulating markers of beta cell stress and death in type 1 diabetes, including markers indicating abnormal prohormone processing, circulating RNAs and circulating DNAs.

Keywords: Biomarker; Diabetes mellitus; Pancreatic beta cells; Pancreatic islets; Review; Type 1 diabetes.

Figures

Fig. 1

Potential conduits for cellular escape of biomolecules: (1) the ER–Golgi secretory network is the physiological pathway through which the processing, folding and secretion of proteins (e.g. insulin, amylin) is routinely achieved in beta cells; (2) the EV pathways are recognised as conduits through which a multitude of biomolecules, including nucleic acids, proteins, lipids and metabolites are released, either through endosomes (exosomes) or plasma membrane outcroppings into EVs (microvesicles); (3) apoptosis/cellular necrosis results in the release of biomolecules within cellular fragments (apoptotic bodies) or directly into circulation (through necrosis and spillage of cellular contents) and represents an end-stage fate of beta cells. MVB, multivesicular body. This figure is available as a downloadable slide