Fulminant type 1 diabetes: recent research progress and future prospects.

Abstract

To clarify the clinical and etiological characteristics of fulminant type 1 diabetes, we reviewed data from patients who had developed type 1 diabetes following anti-programmed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) therapy, and research on pancreatic beta cells derived from induced pluripotent stem (iPS) cells from patients with fulminant type 1 diabetes. As determined from the disease classifications and clinical and genetic characteristics, anti-PD-1/PD-L1 therapy-related type 1 diabetes includes both fulminant type 1 diabetes and acute-onset type 1 diabetes. Using insulin-positive cells derived from iPS cells, beta-cell fragility to inflammatory cytokines, but not its regeneration failure, was observed in fulminant type 1 diabetes. Moreover, severe hyperglycemia was reported as a risk factor of sudden death or cardiac arrest at disease onset, diffusion-weightedmagnetic resonance imaging was suggested as an additional tool for making a diagnosis, and the CSAD/lnc-ITGB7-1 locus was genetically associated with fulminant type 1 diabetes. To fully understand fulminant type 1 diabetes, it is important to clarify the molecular mechanisms step by step through multifaceted approaches such as through analyses of the genetic factors, clinical features, histological findings, and cell biology. The careful and detailed study of patients is a great means for clarifying the etiology and pathophysiology of the disease.