Sims, Emily K.Mirmira, Raghavendra G.Evans-Molina, Carmella2023-03-022023-03-022020-08Sims EK, Mirmira RG, Evans-Molina C. The role of beta-cell dysfunction in early type 1 diabetes. Curr Opin Endocrinol Diabetes Obes. 2020;27(4):215-224. doi:10.1097/MED.0000000000000548https://hdl.handle.net/1805/31567Purpose 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.en-USPublisher PolicyType 1 Diabetesβ cell dysfunctionβ cell biomarkersβ cell healthMetabolic dysfunctionC-peptideInsulinArticle