Studies on Insulin Autoimmune Syndrome

胰岛素自身综合征（IAS）的病因学及其产生自发性严重低血糖的机制已被研究。我们收集了148例日本IAS患者的临床资料，并在实验室对其中部分患者的胰岛素及胰岛素自身抗体进行了分析。结果如下：1。148例患者（男72例，女76例）按首次发生低血糖症的年龄分10年，60例（69岁）为高峰。IAS在老年人中比在年轻人中更常见。HLA-Bl5（Bw62）、Cw4和DR4在IAS患者中的表达明显高于日本普通人群。3 .对IAS患者血清中提取的胰岛素进行HPLC分析，发现其保留时间与合成的人胰岛素相同。对6例低血糖期患者血清中胰岛素自身抗体的Scatchard分析显示，这种特殊的解离模式似乎可以合理地使胰岛素从抗体中释放出来。在148例患者中，至少有54例患者在IAS首次发作前服用了分子中含有SH基团的药物，如甲巯咪唑和硫proproin。这些药物可能成为诱发胰岛素自身抗体的因素之一。在体外实验中，甲巯咪唑对胰岛素的作用没有改变，HPLC分析证实了这一点。

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.