Studies on Insulin Autoimmune Syndrome

胰岛素自身综合征(IAS)的病因学和在该综合征中产生自发性严重低血糖的机制已被研究。本实验室收集了148例日本IAS患者的临床资料，并对其中部分患者血清中的胰岛素及胰岛素自身抗体进行了分析，结果如下：1.将148例IAS患者(男72例，女76例)按首次低血糖发病年龄分为十年，以60~69岁为高峰。结论：1.IAS在老年人中的诊断频率高于年轻人。在IAS患者中，HLA-Bl5(Bw62)、CW4和DR4的出现频率明显高于日本普通人群。对IAS患者血清中提取的胰岛素进行高效液相色谱分析，发现其保留时间与合成的人胰岛素相同。对降糖期6例患者血清中胰岛素自身抗体的Scatchard分析表明，该抗体具有特殊的解离模式，这似乎是产生抗体释放胰岛素的合理途径。在148名患者中，至少有54名患者在其分子中含有SH基团的药物，如他巴唑和硫普罗宁，在IAS首次发作之前就已经服用过。这些药物可能成为激发胰岛素自身抗体的因素之一。体外实验表明，胰岛素与他巴唑孵育后，胰岛素的性质没有发生改变，这一点经高效液相色谱分析证实。

An etiology of the insulin auto syndrome (IAS) and a mechanism to produce spontaneous severe hypoglycemia in this syndrome have been studied. Clinical data of 148 Japanese patients with IAS were collected from each case report, and insulin and insulin autoantibodies in the sera obtained from some patients among those 148 patients were analyzed in our laboratory.Results were as follows:1. When those 148 patients ( 72 males and 76 females ) were divided into each decade according to the age of onset of their first attack of hypoglycenda, the peak of the number was found in 60 69-year-old. IAS was diagnosed more frequently in the old people than in the young.2. HLA-Bl5(Bw62), Cw4 and DR4 were found much more frequently in the patients with IAS than in Japanese general population.3. HPLC analysis of the extracted insulin from the sera of the patients with IAS revealed the same retention time as that of the synthesized human insulin.4. Scatchard analysis of the insulin autoantibodies in the sera of six patients obtained during the hypoglycemic periods showed the particular dissociation patterns which seemed reasonable to produce the release of insulin from the antibodies.5. Drugs containing a SH group in their molecules, such as methimazole and tiopronin, had been administered before the first attack of IAS at least in 54 among the 148 patients. Those drugs might become one of factors of provocation of insulin autoantibodies. As an experiment in vitro, incubation of insulin with methimazole revealed no change of the nature of insulin which was proved bv HPLC analysis.