The role of beta-cell dysfunction in early type 1 diabetes

作者：Emily K. Sims, Raghavendra G. Mirmira, Carmella Evans‐Molina · 发表于：Current Opinion in Endocrinology Diabetes and Obesity · 年份：2020 · DOI：10.1097/med.0000000000000548 · 被引用次数：83 · 研究领域：Diabetes and associated disorders、Pancreatic function and diabetes、Diabetes Management and Research

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.