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-weighted magnetic 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. KeywordsFulminant type 1 diabetes • Immune checkpoint molecules • PD-1 • Induced pluripotent stem cells * Akihisa Imagawa

Fulminant type 1 diabetes with normal serum amylase: a case report

“…Our clinical outcomes in this case accorded with the diagnostic standards for FT1D. Genetic and environmental factors influence the pathogenesis of FT1D [8] . With regard to genetic factors, susceptibility to progression to FT1D is related to HLA class II genes.…”

Acid-driven immune suppression by pHLIP-fused PD-L1 under inflammatory conditions

“…Para n-embedded sections were stained for hematoxylin-eosin (HE). Colitis score was undertaken according to the criteria described previously 39 . For immunohistochemistry of mouse colon tissue, slides were incubated with primary antibody against SLC26A3 (1:200) (Novusbio, NBP1-84450) in PBS containing 1% BSA and 10% goat serum.…”

Identification of hsa_circRNA_100632 as a novel molecular biomarker for fulminant type 1 diabetes

“…Fulminant type 1 diabetes (FT1D) is a novel subtype of type 1 diabetes (T1D) first identified by Imagawa et al in 2000 (1,2). FT1D is characterized by aggressive disease onset, dramatic loss of Cpeptide concentration, nearly normal levels of hemoglobin A1c (HbA1c) at onset, and diabetic ketoacidosis (DKA) (3,4). Failure to accurately diagnose FT1D can result in death (5,6).…”