Fulminant type 1 diabetes: 20 years of discovery and development

Twenty years have passed since the first article on fulminant type 1 diabetes (FT1D) was published. FT1D is characterized by an extremely rapid onset of ketoacidosis, high plasma glucose and, conversely, a near-normal glycosylated hemoglobin level. Digestive or flu-like symptoms frequently precede the onset of ketoacidosis. Patients are usually negative for islet-related autoantibodies, with near-complete destruction of pancreatic β-cells, even at the onset of disease. Massive infiltration of immunocytes (insulitis) can be seen in the islets of patients with new-onset FT1D, but this subsides within a few weeks. Early discovery and development of research on FT1D were carried out in Japan, with some reports from Korea and China. Recently, the recognition of FT1D as an immune-related adverse effect of immune-checkpoint inhibitor therapy for various malignant tumors in some patients has drawn the attention of Western countries. The discovery and successful establishment of FT1D as a disease entity was the product of three essential factors: (1) accumulated research data spanning more than 10 years; (2) fortuitous clinical observation; and (3) organization of a dedicated Japanese research committee. We anticipate that continued investigations of FT1D by a new generation of researchers will further elucidate the pathogenesis and yield new therapies.