Etiology of fulminant type 1 diabetes

暴发性 1 型糖尿病的病因学

• 批准号: 14370342
• 负责人: HANAFUSA Toshiaki
• 金额: $ 8.96万
• 依托单位: Osaka Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370342/
• 关键词: fulminant; diabetes; type 1; HLA; biopsy; enterovirus; Elispot; immunohistochemistry; 1型糖尿病; 劇症1型糖尿病; ウイルス; 自己免疫; α細胞; β細胞; 膵島炎

We have clarified the etiology of fulminant type 1 diabetes, a novel subtype of type 1 diabetes, from the aspects of epidermiology, genetics, histology, virology and immunology.Epidemiological analysis of 161 patients of fulminant type 1 diabetes has revealed frequent flu-like symptoms (71.7%) and abdominal symptoms (72.5%) before the onset of the disease (Diabetes Care 2003).HLA analysis has shown that DR4 is predominant in fulminant type 1 diabetes but DR9 is not. DR2 was not resistant to fulminant type 1 diabetes (submitted). Genetic analysis has further revealed DRB1*0405-DQB1*0401 is predominant in fulminant type 1 diabetes (in preparation).By the examination of pancreatic biopsy specimens of fulminant type 1 diabetic patients, not only beta cells but also alpha cells were destructed, suggesting a molecular mechanism destroying both beta and alpha cells (in preparation).We have also identified the elevation of enterovirus antibodies in the serum of recent-onset fulminant type 1 diabetic patients (in preparation) and the activation of beta cell reactive Th1 T cells by using Elispot assay in those patients (in preparation).

我们从表皮学、遗传学、组织学等方面阐明了暴发型1型糖尿病的病因，对161例暴发性1型糖尿病患者的流行病学分析显示，在疾病发作之前，DR 4（71.7%）和腹部症状（72.5%）（Diabetes Care 2003）ALA分析已经显示，DR 4在暴发性1型糖尿病中占优势，但DR 9不是。DR 2对暴发性1型糖尿病不耐药（已提交）。遗传分析进一步揭示DRB 1 *0405-DQB 1 *0401在暴发性1型糖尿病中占主导地位通过检查暴发性1型糖尿病患者的胰腺活组织检查样本，不仅β细胞而且α细胞被破坏，这表明一种分子机制同时破坏了β细胞和α细胞我们还发现在新近发作的暴发性1型糖尿病患者血清中肠道病毒抗体升高（制备中）和通过使用Elispot测定在这些患者中活化β细胞反应性Th 1 T细胞（制备中）。

项目成果

Q.Yang, T.Hanafusa, et al.: "Hepatocyte nuclear factor-1α modulates pancreatic β-cell growth by regulating the expression of insulin-like growth factor-1 in INS-1 cells"Diabetes. 51・6. 1785-1792 (2002)

Q.Yang、T.Hanafusa 等人：“肝细胞核因子 1α 通过调节 INS-1 细胞中胰岛素样生长因子 1 的表达来调节胰腺 β 细胞生长”糖尿病 51・6。 1792 (2002)

Imagawa A, Miyagawa J, et al.: "Beta-cell regeneration in a patient with type 1 diabetes mellitus who was receiving immunosuppressive therapy"Ann Intern Med. 139. W81 (2003)

Imakawa A、Miyakawa J 等人：“接受免疫抑制治疗的 1 型糖尿病患者的 β 细胞再生”Ann Intern Med。

花房 俊昭: "1型糖尿病の理解の新しい展開"Medical Practice. 20・5. 807 (2003)

Toshiaki Hanabusa：“了解 1 型糖尿病的新进展”医学实践 20・5。

Imagawa A, Hanafusa T, et al.: "Association of fulminant type I diabetes with pregnancy"Diabetes Res Clin Pract. 62. 33-38 (2003)

Imakawa A、Hanafusa T 等人：“暴发性 I 型糖尿病与妊娠的关系”糖尿病研究临床实践。

花房俊昭, 今川彰久: "劇症1型糖尿病"医学のあゆみ. 207. 708-713 (2003)

Toshiaki Hanafusa、Akihisa Imakawa：“暴发性 1 型糖尿病”医学史 207. 708-713 (2003)。