mechanism of insulin autoantibody production for pathogenesis of pancreatic beta cell destruction and hyperplasia

胰岛素自身免疫综合征（IAS）和1型糖尿病都以胰岛素自身抗体为特征.另一方面，胰岛素抗体或抗胰岛素抗体是皮下注射的针对胰岛素的抗体。胰岛素抗体和胰岛素自身抗体都具有结合人血清中胰岛素的能力。自1970年Hirata报道以来，我们收集了日本244例胰岛素自身免疫综合征（IAS）患者的病历，至1997年，平均每年发生9例IAS。我们收集了1998年至1999年11例IAS患者，收集了2000年至2003年19例IAS患者。国际会计准则的发展没有增加。2003年底收集了274例胰岛素自身免疫综合征患者。其中38%的人在IAS发展之前接受过巯基化合物如甲巯咪唑、噻托溴铵和噻托溴铵的治疗。从国际会计准则的发生率来看，没有逐年上升的趋势。部分患者在发生IAS后出现餐后高血糖。收集葡萄糖耐量试验（GTT）结果。GTT组中糖尿病型占59%，IGT型占38%。这表明约90%的患者显示出糖代谢异常。使用125 I-人胰岛素通过Scatchard分析进行胰岛素自身抗体的表征。胰岛素自身抗体的主要部位为高亲和力（k1）-低容量（b1）位点，并与胰岛素治疗的糖尿病患者的胰岛素抗体进行了比较。胰岛素治疗的糖尿病患者的k1和b1分别大于1x10^8 L/mol和约1或小于1x10^8 mol/L，而IAS患者的k1和b1分别小于1x10^8 L/mol和大于1x10^8 mol/L。有显著性差异（p<0.001）。

Both of insulin autoimmune syndrome (IAS) and type 1 diabetes are characterized by insulin autoantibody. On the other hand, insulin antibody or anti-insulin antibody is a antibody against insulin which is injected subcutaneously. The insulin antibody and the insulin autoantibody have both an ability to bind insulin in human serum. Since reported by Hirata in 1970, we collected 244 patient record with insulin autoimmune syndrome (IAS) in Japan until 1997, which showed a development of averaged 9 patients with IAS per year. We collected 11 patients with IAS from 1998 to 1999, and collected 19 patients with IAS from 2000 to 2003. There was no increase of the development of IAS. Total of 274 patients with insulin autoimmune syndrome were collected in the end of 2003. Thirty-eight % of them was treated with sulfhydroxy compounds such as Methimazole, Thiola and Tathione before the development of IAS. According to the incidence of IAS, there was no increase year by year. Some of the patients had postprandial hyperglycemia after the development of IAS. the outcome of glucose tolerance test (GTT) was collected. Among them who were performed GTT, 59% had diabetic pattern, 38% had IGT pattern. It suggests that approximately 90% showed abnormal glucose metabolism. The characterization of the insulin autoantibody was done by Scatchard analysis using 125 I-human insulin. A major part of the insulin autoantibody was a high affinity (k1)-low capacity (b1) site, the site was compared with that of insulin antibody which were found in insulin-treated diabetic patients. The k1 and b1 were more than 1x10^8 L/mol and around 1 or less than 1x10^8 mol/L, respectively in insulin-treated diabetic patients, whereas those were less than 1x10^8 L/mol and more than 1x10^8 mol/L, respectively in the patients with IAS. There was a significant difference (p<0.001).