Fulminant type 1 diabetes is a novel subtype of type 1 diabetes identified in 20001–3. It is defined as diabetes that results from the extremely rapid and almost entire destruction of pancreatic β-cells within a few days. The clinical characteristics of this subtype are different in many aspects from those of typical type 1A diabetes3. Although fulminant type 1 diabetes resembles the typical form of type 1 diabetes in that it is characterized by high plasma glucose levels accompanied by ketosis or ketoacidosis, it clearly differs by an extremely acute onset of diabetes, which is confirmed by nearly normal HbA1c levels against high plasma glucose concentration, and virtually no C-peptide secretion at the onset of the disease, indicating that the process of pancreatic β-cell destruction is very rapid.
Fulminant type 1 diabetes is common in the Asian population; it accounts for approximately 20% of ketosis-onset type 1 diabetes in Japan2,3 and 7% in Korea4,5. Furthermore, several cases have been reported from China6, Taiwan7, the Philippines8, Malaysia9 and France10.
It is suggested that both genetic factors11–13 and environmental factors, such as viral infection14–19, contribute to the pathogenesis of this disease. In regard to genetic factors, it has been reported that class II HLA strongly confers susceptibility to the development of fulminant type 1 diabetes. In the analysis of the serological typing of class II HLA, we have shown that HLA-DR4-DQ4 was significantly more frequent in fulminant type 1 diabetes in Japan12. Several studies have so far reported the association of class II HLA genotype with fulminant type 1 diabetes20–22; however, the number of patients was limited in these reports as a result of the low incidence of type 1 diabetes in general, fulminant type 1 diabetes in particular, in the Japanese population.
The aim of the present study was thus to investigate the class II HLA genotypes and re-evaluate the contribution of the class II HLA to susceptibility and resistance to fulminant type 1 diabetes in a large number of patients.