Aims/Introduction:  Fulminant type 1 diabetes is a subtype of type 1 diabetes characterized by a remarkably abrupt onset of insulin‐deficient hyperglycemia within a few days. The aim of the present study was to clarify characteristic class II HLA genotypes in a large number of patients with fulminant type 1 diabetes to date.Materials and Methods:  We analyzed the HLA‐DRB1 and DQB1 genotypes, and their haplotypes in 207 patients with fulminant type 1 diabetes and 325 control subjects in the Japanese population.Results:  The frequencies of the DRB1*04:05‐DQB1*04:01 and DRB1*09:01‐DQB1*03:03 haplotypes were significantly higher, and those of the DRB1*01:01‐DQB1*05:01, DRB1*15:02‐DQB1*06:01 and DRB1*08:03‐DQB1*06:01 haplotypes were significantly lower in patients with fulminant type 1 diabetes than in the control subjects. Combination analysis showed that the frequencies of homozygotes with DRB1*04:05‐DQB1*04:01 [odds ratio (OR) 7.0] and DRB1*09:01‐DQB1*03:03 (OR 9.5) were significantly higher in patients with fulminant type 1 diabetes. Within a limited portion of patients with fulminant type 1 diabetes with antibodies to glutamic acid decarboxylase (GADab; n = 25), the frequency of DRB1*09:01‐DQB1*03:03, but not DRB1*04:05‐DQB1*04:01, was significantly higher than in control subjects (44.0% vs 13.7%; Pc < 0.05, OR 5.0).[Correction to last line of Results, added after online publication 29 July 2011: “OR 5.1” is changed to “OR 5.0”.]Conclusions:  Our large‐scale study showed the characteristic class II HLA genotypes in fulminant type 1 diabetes, and implicated that genetic contribution to disease susceptibility is distinct between GADab‐positive and GADab‐negative fulminant type 1 diabetes. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00139.x, 2012)

SummaryProgrammed cell death-1 (PD-1) is a co-stimulatory molecule that inhibits T cell proliferation. We aimed to clarify PD-1 expression in CD41 T cells and the association between PD-1 expression and the 7785C/T polymorphism of PDCD1, with a focus on the two subtypes of type 1 diabetes, type 1A diabetes (T1AD) and fulminant type 1 diabetes (FT1D), in the Japanese population. We examined 22 patients with T1AD, 15 with FT1D, 19 with type 2 diabetes (T2D) and 29 healthy control (HC) subjects. Fluorescence-activated cell sorting (FACS) and real-time PCR were utilized to analyse PD-1 expression quantitatively.Genotyping of 7785C/T in PDCD1 was performed using the TaqMan method in a total of 63 subjects (21 with T1AD, 15 with FT1D and 27 HC). FACS revealed a significant reduction in PD-1 expression in CD4 1T cells in patients with T1AD (mean: 4Á2 vs. 6Á0% in FT1D, P 5 0Á0450; vs. 5Á8% in T2D, P = 0Á0098; vs. 6Á0% in HC, P 5 0Á0018). PD-1 mRNA expression in CD4 1 T cells was also significantly lower in patients with T1AD than in the HC subjects. Of the 63 subjects, PD-1 expression was significantly lower in individuals with the 7785C/C genotype than in those with the C/T and T/T genotypes (mean: 4Á1 vs. 5Á9%, P 5 0Á0016). Our results indicate that lower PD-1 expression in CD4 1 T-cells might contribute to the development of T1AD through T cell activation.

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We isolated osteoblastic cells derived from human periosteum and established them in culture. Their growth depended on the presence of ascorbic acid, and the doubling time was 40 to 60 h. The requirement for ascorbic acid was used to high production of collagen. These cells produced mainly type I collagen and only small amounts of type III collagen determined by reducing sodium dodecyl sulfate SDS-polyacrylamide gel electrophoresis. The total collagen yield was about 10 mg from 2 X 10(7) cells. The cells could be continuously cultured in alpha-minimum essential medium supplemented with 10% fetal bovine serum for 18 to 40 population doubling levels, depending on the age of the donated periosteum. These cells have the ability to calcify when incubated with 2 mM alpha-glycerophosphate-Na2. Calcification as viewed by the naked eye appeared from Day 15 after treatment. Treatment with the active formed vitamin D3, 1, 25 dihydroxyvitamin D3 enhanced calcification significantly and stimulated osteocalcin production. By electron microscopy, cells with many projections on their surfaces showed well-developed rough endoplasmic reticulum and actinlike fibers, and larger numbers of lysosomes, mitochondria, and secretion granules. Many matrix vesicles, in which minerals were initially localized, and well-banded collagen fibrils were seen in the intercellular spaces. These observations demonstrate typical osteoblastic morphology. The above results indicate that cultured cells from human periostem are osteoblastic cells that have the capacity to differentiate into osteocytes and to deposit calcified minerals in response to 1,25 dihydroxyvitamin D3.