OBJECTIVE -To describe the clinical and immunologic characteristics of fulminant type 1 diabetes, a novel subtype of type 1 diabetes, we conducted a nationwide survey.RESEARCH DESIGN AND METHODS -History and laboratory data, including isletrelated autoantibodies, were examined in 222 patients with fulminant and nonfulminant type 1 diabetes in our hospitals in addition to another 118 patients with fulminant type 1 diabetes located outside our hospitals in Japan.RESULTS -In our hospitals, of the 222 patients studied, 43 (19.4%) were diagnosed with fulminant type 1 diabetes, 137 (61.7%) were classified as having autoimmune type 1 diabetes, and 42 were type 1 diabetic subjects who were not fulminant and did not have anti-islet antibodies. An additional 118 fulminant patients outside our hospitals were enrolled, making a total of 161 fulminant type 1 diabetic subjects (83 male and 78 female subjects; 14 children/ adolescents and 147 adults) identified from all over Japan. (In 2000, the average incidence was three cases per month.) Flu-like symptoms and pregnancy were more frequently observed in the fulminant than in the autoimmune group (P Ͻ 0.001). In the fulminant patients, 4.8% were positive for anti-GAD antibodies and none were positive for anti-islet antigen 2 antibodies.CONCLUSIONS -Fulminant type 1 diabetes is a distinct subtype and accounts for ϳ20% of the ketosis-onset type 1 diabetes cases in Japan. Flu-like symptoms are characteristic of disease onset. Metabolic derangement is more severe in this subtype than in autoimmune type 1 diabetes. Diabetes Care 26:2345-2352, 2003T ype 1 (insulin-dependent) diabetes is characterized by insulin deficiency from the destruction of pancreatic ␤-cells. According to the recently proposed classification of diabetes by the American Diabetes Association (ADA) and the World Health Organization (WHO), type 1 diabetes is divided into two subtypes: autoimmune type 1 (immune-mediated; type 1A) diabetes and idiopathic (type 1B) diabetes (1,2).Since 1974, when Bottazzo et al. (3) reported the presence of islet cell antibodies (ICAs) in the sera of type 1 diabetic patients, several autoantibodies to pancreatic islet cells have been recognized as a marker of type 1 diabetes. These isletrelated autoantibodies are anti-GAD antibodies (GADAb), insulin autoantibodies (IAA), and anti-islet antigen 2 (IA-2)/ IA-2␤ antibodies (4,5).However, type 1 diabetic patients are not always positive for these autoantibodies, even at the onset of overt diabetes (6,7). Patients with type 1 diabetes who do not have islet autoantibodies at the time of diagnosis are classified as having idiopathic or type 1B diabetes. In Japan, several cases have been reported in which islet-related autoantibodies were negative and the onset of diabetes was acute (8 -12). Imagawa and colleagues (13,14) have proposed that these cases are "nonautoimmune fulminant" type 1 diabetes. The clinical characteristics of this subtype of type 1 diabetes are 1) remarkably abrupt onset of disease; 2) very short (Ͻ1 week) duration of di...

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We have revised a part of the diagnostic criteria for fulminant type 1 diabetes. The new criteria were set both to express the essence of this disease of rapid increase of patients' blood glucose and to be highly sensitive to reduce the misdiagnosis. After analyzing the data of 382 patients with newly-diagnosed fulminant type 1 diabetes, we adopted the glycated hemoglobin (HbA 1c ) level of 8.7% (National Glycohemoglobin Standardization Program [NGSP] value). The new criterion indicates 100% of sensitivity and the best value by receiver operating characteristic curve analysis. In addition, we added a comment that 'This value (HbA 1c <8.7% in NGSP) is not applicable for patients with previously diagnosed glucose intolerance' in the new criteria and also a comment that 'Association with human leukocyte antigen DRB1*04:05-DQB1*04:01 is reported' as a related finding. We did not revise the screening criteria and the other part of the diagnostic criteria, because they are still reliable. (J Diabetes Invest

To assess the effect of Asian-specific HLA haplotypes on susceptibility to type 1 diabetes, we investigated the association of genotypic combinations of DRB1-DQB1 haplotypes with susceptibility to type 1 diabetes. We studied 132 Japanese patients with type 1 diabetes and 157 control subjects, along with 67 Korean patients and 109 control subjects. DRB1*0405-DQB1*0401 and DRB1*0901-DQB1*0303 were confirmed to be two major susceptible HLA haplotypes in the Japanese population. The frequencies of heterozygotes and homozygotes with DRB1*0405-DQB1*0401 were similarly higher in patients than in control subjects (homozygotes, 5.3% vs. 3.8%; heterozygotes, 48.5% vs. 26.1%). In contrast, homozygotes, but not heterozygotes, with DRB1*0901-DQB1*0303 were more frequent in patients with type 1 diabetes than in control subjects (homozygotes, 12.9% vs. 0.6%; heterozygotes, 22.0% vs. 24.8%). A similar tendency was also observed in the Korean population. In multiple logistic regression analysis, DRB1*0405-DQB1*0401 fitted a dominant model and DRB1*0901-DQB1*0303 fitted a recessive model. These data, which indicate that the contribution of HLA haplotypes to the genetic susceptibility to type 1 diabetes differs depending on the genotypic combination of HLA haplotypes, suggest the importance of extensive analysis of genotypes in studies on HLA and disease association in general. Diabetes 51:545-551, 2002

One of the most common complications of diabetes is diabetic foot ulcer. Diabetic ulcers do not heal easily due to diabetic neuropathy and reduced blood flow, and nonhealing ulcers may progress to gangrene, which necessitates amputation of the patient's foot. This study attempted to develop a new cell-based therapy for nonhealing diabetic ulcers using a full-thickness skin defect in a rat model of type 2 diabetes and obesity. Allogeneic adipose-derived stem cells (ASCs) were harvested from the inguinal fat of normal rats, and ASC sheets were created using cell sheet technology and transplanted into full-thickness skin defects in Zucker diabetic fatty rats. The results indicate that the transplantation of ASC sheets combined with artificial skin accelerated wound healing and vascularization, with significant differences observed 2 weeks after treatment. The ASC sheets secreted large amounts of several angiogenic growth factors in vitro, and transplanted ASCs were observed in perivascular regions and incorporated into the newly constructed vessel structures in vivo. These results suggest that ASC sheets accelerate wound healing both directly and indirectly in this diabetic wound-healing model. In conclusion, allogeneic ASC sheets exhibit potential as a new therapeutic strategy for the treatment of diabetic ulcers.

These findings suggest the value of measuring health status in diabetes mellitus patients, because it is able to comprehensively evaluate the patient's health condition, and add another dimension to the subjective symptoms and laboratory data.

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The incidence of nephropathy has declined in Japanese patients with type 1 but not in those with type 2 diabetes. In young Japanese patients, because of the higher incidence of nephropathy in type 2 diabetes and the higher prevalence of type 2 than type 1 diabetes, type 2 diabetes is likely the major cause of diabetic nephropathy.