两种胰岛细胞抗体染色亚型与糖尿病的关系

目的 调查胰岛细胞抗体（ICA）亚型与自身免疫性糖尿病（DM）临床表现多样性间的关系。方法 收集急性起病Ⅰ型DM（58例）、成人隐匿性自身免疫性DM（LADA，45例）、2型DM（325例）及正常对照组（59例）血清，ICA用间接免疫过氧化物酶法测定。根据ICA染色形态对全部ICA阳性血清进行亚型划分，再用患者血清和抗胰高血糖素抗体或抗胰岛素抗体进行免疫双重染色，鉴定不同ICA亚型着染的胰岛细胞类型。结果 ICA在1型DM、LADA、2型DM及正常对照者的阳笥率分别为67.24%1、51.11% 、9.54%、1.69%。在光镜下，ICA可区分为两种染色形态：使整个胰岛弥漫着色的称为弥漫型，仅使胰岛周边的部分细胞着色的称为边缘型。免疫双重染色证实，弥漫型ICA使胰岛α、β细胞着染，边缘型ICA仅使α细胞着染。2型DM中边缘型ICA的比例（18／31）显著高于1型DM（4／39）或LADA（3／23）（P＜0.001)。DM患者中，弥漫型ICA与边缘型ICA比较，前者发病年龄轻、空腹血糖高、残存胰岛功能差。结论 临床上诊断为2型DM的患者中有9％可能为LADA。自身免疫性DM的临床亚型与不同的ICA染色亚型有一定联系，弥漫型ICA患者病情重，进展较快，而边缘型ICA可能与缓慢进展的β细胞损伤有关。

The relationship of two subsets of islet cell cytoplasmic autoantibodies to diabetes mellitus

Objective　To investigate whether the islet cell antibodies (ICA) subsets were associated with the heterogeneous presentations of autoimmune diabetes mellitus (DM). Methods　ICA was measured by indirect immunoperoxidase method in sera from patients diagnosed as acute-onset type 1 DM (n=58), latent autoimmune diabetes in adults (LADA, n=45), type 2 DM (n=325) and normal control subjects (n=59). All ICA positive sera were classified according to the patterns of ICA staining on islet. Double immunostaining of patient's serum and anti-glucagon antibody or anti-insulin antibody were applied for identification of islet cell-types stained by different ICA subsets. Results　(1)The positive rates of ICA in Chinese patients　　with acute-onset type 1 DM, LADA, and　　type　　2 DM　　and　　control subjects were 67.24%, 51.11%, 9.54% and 1.69%, respectively. (2)Under light microscope, two ICA staining patterns were discriminated: one diffuse staining pattern in both α and β islet-cells stained and the other, peripheral pattern only in the peripheral α cells stained. (3)The peripheral pattern in the patients with type 2 DM (18/31) was more frequent than those with acute-onset type 1 DM (4/39) or LADA (3/23) (P＜0.001). Compared with those with peripheral pattern ICA, the patients with diffuse staining pattern of ICA were younger at onset, and had higher fasting blood glucose levels and less residual islet function. Conclusion　In patients with type 2 DM, the incidence of LADA may be at least 9%. Clinical subtypes of autoimmune diabetes are associated with the different ICA staining subsets which may reflect distinct courses of the autoimmune response correlated with rapidly acute or slowly progressive destruction of the β-cell.