ObjectiveFulminant type 1 diabetes may uniquely occur as a fatal adverse event during immune checkpoint inhibitor (ICI) therapy. We investigated the clinical and immunological characteristics of ICI-associated fulminant type 1 diabetes (IFD).Research design and methodsWe enrolled 80 patients with IFD (77 cases from the literature), 56 patients with ICI-associated type 1 diabetes (IT1D) (55 cases from the literature), 45 patients with traditional fulminant type 1 diabetes (TFD), and 43 patients with acute-onset type 1 diabetes for comprehensive analysis including islet autoantibodies and subgroup analysis based on ethnic origin.ResultsPatients with IFD accounted for 58.8% (80/136) of patients with ICI-related diabetes. IFD had a more rapid onset than IT1D after ICI therapy (90.5 days vs. 120 days, p <0.05). The onset time and number of infusions after ICI therapy initiation were lower in the antibody-positive IFD group than that in the antibody-negative IFD group (both p <0.001). IFD had a more rapid onset and more serious among Caucasians than that among Asians (p <0.01, p <0.05, respectively), and the prevalence of islet autoantibody positivity in the Caucasian IFD were prominently higher than those in the Asian IFD (p <0.05). Onset age and plasma glucose levels were significantly higher in the IFD group than those in the TFD and acute-onset type 1 diabetes groups. HbA1c levels were slightly higher in patients with IFD than those with TFD.ConclusionsIFD is relatively common in Caucasian population where TFD is very rare or almost absent. IFD occurrence is significantly related to islet autoantibody status and ethnic origin.
A novel class of non-coding RNA transcripts called circular RNAs (circRNAs) have been the subject of significant recent studies. Accumulating evidence points that circRNAs play an important role in the cellular processes, inflammatory expression, and immune responses through sponging miRNA, binding, or translating in proteins. Studies have found that circRNAs are involved in the physiologic and pathologic processes of diabetes. There has been an increased focus on the relevance of between abnormal circRNA expression and the development and progression of various types of diabetes and diabetes-related diseases. These circRNAs not only serve as promising diagnostic and prognostic molecular biomarkers, but also have important biological roles in islet cells, diabetes, and its complications. In addition, many circRNA signaling pathways have been found to regulate the occurrence and development of diabetes. Here we comprehensively review and discuss recent advances in our understanding of the physiologic function and regulatory mechanisms of circRNAs on pancreatic islet cells, different subtypes in diabetes, and diabetic complications.
Latent autoimmune diabetes in adults (LADA) is a heterogeneous disease sharing some phenotypic, genetic, and immunological features with both type 1 and 2 diabetes. Patients with LADA have a relatively slow autoimmune process and more residual islet β-cell function at onset, allowing a time window to protect residual islet β cells and delay or inhibit disease progression. It is crucial to discover various heterogeneous factors affecting islet β-cell function for precise LADA therapy. In this review, we first describe the natural history of LADA. Thereafter, we summarize β-cell function-related heterogeneous factors in LADA, including the age of onset, body mass index, genetic background, and immune, lifestyle, and environmental factors. In parallel, we evaluate the impact of current hypoglycemic agents and immune intervention therapies for islet β-cell protection. Finally, we discuss the opportunities and challenges of LADA treatment from the perspective of islet β-cell function protection.
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