First Department of Internal Medicine, Osaka Medical College, Japan.
Endocr J. 2010;57(3):211-9. doi: 10.1507/endocrj.k09e-291. Epub 2009 Dec 12.
Fulminant type 1 diabetes, established in 2000, is defined as a novel subtype of diabetes mellitus that results from remarkably acute and almost complete destruction of pancreatic beta cells at the disease onset. In this study, we aimed to clarify the pathogenesis of fulminant type 1 diabetes with special reference to insulitis and viral infection. We examined pancreatic autopsy samples from three patients who had died soon after the onset of disease and analyzed these by immunohistochemistry and in situ-hybridization. The results were that both beta and alpha cell areas were significantly decreased in comparison with those of normal controls. Mean beta cell area of the patients just after the onset was only 0.00256 % while that of normal control was 1.745 %. Macrophages and T cells-but no natural killer cells-had infiltrated the islets and the exocrine pancreas. Although both of them had massively infiltrated, macrophages dominated islet infiltration and were detected in 92.6 % of the patients' islets. Toll-like receptor (TLR) 3, a sensor of viral components, was detected in 84.7+/- 7.0 % of T cells and 62.7+/- 32.3 % of macrophages (mean+/- SD) in all three patients. TLR7 and TLR9 were also detected in the pancreas of all three patients. Enterovirus RNA was detected in beta-cell positive islets in one of the three patients by in situ-hybridization. In conclusion, our results suggest that macrophage-dominated insulitis rather than T cell autoimmunity contributes to beta cell destruction in fulminant type 1 diabetes.
暴发性 1 型糖尿病于 2000 年被确立，其定义为一种新型糖尿病亚型，由疾病发作时胰腺β细胞显著急性和几乎完全破坏引起。在本研究中，我们旨在阐明暴发性 1 型糖尿病的发病机制，特别关注胰岛炎和病毒感染。我们检查了三位疾病发作后不久死亡的患者的胰腺尸检样本，并通过免疫组织化学和原位杂交进行了分析。结果表明，与正常对照组相比，β和α细胞区均显著减少。患者发病后即刻的平均β细胞面积仅为 0.00256%，而正常对照组为 1.745%。巨噬细胞和 T 细胞——但没有自然杀伤细胞——已浸润胰岛和外分泌胰腺。尽管它们都大量浸润，但巨噬细胞主导胰岛浸润，在 92.6%的患者胰岛中检测到。Toll 样受体 (TLR)3 是病毒成分的传感器，在所有 3 名患者的 84.7+/-7.0%的 T 细胞和 62.7+/-32.3%的巨噬细胞（平均值+/-标准差）中均被检测到。TLR7 和 TLR9 也在所有 3 名患者的胰腺中被检测到。通过原位杂交，在一名患者的胰岛阳性β细胞中检测到肠道病毒 RNA。总之，我们的结果表明，巨噬细胞主导的胰岛炎而不是 T 细胞自身免疫导致暴发性 1 型糖尿病中β细胞破坏。
