Concepts of Beta-Cell Organ Dysfunction and Failure Would Lead to Earlier Diagnoses and Prevention

As the world endures a viral pandemic superimposed on a diabetes pandemic, the latter incorporates most of the comorbidities associated with the former, thereby exacerbating risk of death in both. An essential approach to both pandemics is prevention and unrealized earlier treatment. Thus, in this Perspective relating to diabetes we emphasize a paradigm of first, reversible beta-cell organ dysfunction (BCOD) and then irreversible beta-cell organ failure (BCOF), which directly indicate the potential for earlier prevention, also unrealized in current guidelines. Four pillars support this paradigm: epidemiology, pathophysiology, molecular pathology, and genetics. A substantial worldwide knowledge base defines each pillar and informs a more aggressive preventive approach to most forms of the disorder. This analysis seeks to clarify the temporal and therapeutic relationships between lost beta-cell function and content, illuminating the potential for earlier diagnoses and thus, prevention. We also propose that myriad pathways leading to most forms of diabetes converge at the endoplasmic reticulum, where stress can result in beta-cell death and content loss. Finally, genetic and nongenetic origins common to major types of diabetes can inform earlier diagnosis and potentially, prevention, with the aim of preserving beta-cell mass.