DIABETES AND ENDOCRINE PANCREAS II: Edited by Peter A. GottliebThe role of beta-cell dysfunction in early type 1 diabetesSims, Emily K.a,b,c,d; Mirmira, Raghavendra G.h; Evans-Molina, Carmellaa,b,c,d,e,f,gAuthor Information aDepartment of Pediatrics bWells Center for Pediatric Research cCenter for Diabetes and Metabolic Diseases dDepartment of Biochemistry and Molecular Biology eDepartment of Medicine fDepartment of Cellular and Integrative Physiology, Indiana University School of Medicine gRoudebush VA Medical Center, Indianapolis, Indiana hKovler Diabetes Center and the Department of Medicine, The University of Chicago, Chicago, Illinois, USA Correspondence to Emily K. Sims, 635 Barnhill Drive, MS2031E, Indianapolis, 46202. E-mail: email@example.com Current Opinion in Endocrinology & Diabetes and Obesity: August 2020 - Volume 27 - Issue 4 - p 215-224 doi: 10.1097/MED.0000000000000548 Buy Metrics Abstract Purpose of review Emerging data have suggested that β-cell dysfunction may exacerbate the development and progression of type 1 diabetes (T1D). In this review, we highlight clinical and preclinical studies suggesting a role for β-cell dysfunction during the evolution of T1D and suggest agents that may promote β-cell health in T1D. Recent findings Metabolic abnormalities exist years before development of hyperglycemia and exhibit a reproducible pattern reflecting progressive deterioration of β-cell function and increases in β-cell stress and death. Preclinical studies indicate that T1D may be prevented by modification of pathways impacting intrinsic β-cell stress and antigen presentation. Recent findings suggest that differences in metabolic phenotypes and β-cell stress may reflect differing endotypes of T1D. Multiple pathways representing potential drug targets have been identified, but most remain to be tested in human populations with preclinical disease. Summary This cumulative body of work shows clear evidence that β-cell stress, dysfunction, and death are harbingers of impending T1D and likely contribute to progression of disease and insulin deficiency. Treatment with agents targeting β-cell health could augment interventions with immunomodulatory therapies but will need to be tested in intervention studies with endpoints carefully designed to capture changes in β-cell function and health. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.