The heterogeneity of islet autoantibodies and the progression of islet failure in type 1 diabetic patients  

作　　者：Jin Liu Lingling Bian Li Ji Yang Chen Heng Chen Yong Gu Bingqin Ma Wei Gu Xinyu Xu Yun Shi Jian Wang Dalong Zhu Zilin Sun Jianhua Ma Hui Jin Xing Shi Heng Miao Bing Xin Yan Zhu Zhenwen Zhang Ruifang Bu Lan Xu Guangde Shi Wei Tang Wei Li Dongmei Zhou Jun Liang Xingbo Cheng Bimin Shi Jixiang Dong Ji Hu Chen Fang Shao Zhong Weinan Yu Weiping Lu Chenguang Wu Li Qian Jiancheng Yu Jialin Gao Xiaoqiang Fei Qingqing Zhang Xueqin Wang Shiwei Cui Jinluo Cheng Ning Xu Guofeng Wang Guoqing Han Chunrong Xu Yun Xie Minmin An Wei Zhang Zhixiao Wang Yun Cai Qi Fu Yu Fu Shuai Zheng Fan Yang Qingfang Hu Hao Dai Yu Jin Zheng Zhang Kuanfeng Xu Yifan Li Jie Shen Hongwen Zhou Wei He Xuqin Zheng Xiao Han Liping Yu Jinxiong She Mei Zhang Tao Yang 

机构地区：[1]Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China [2]Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado 80045, USA [3]Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing 210000, China [4]Department of Isotopic Laboratory of Nanjing Medical University, Nanjing 210000, China [5]HLA Laboratory of Jiangsu Province People's Hospital, Nanjing 210029, China [6]Department of Endocrinology and Metabolism, Nanjing General Hospital of Nanjing Military Command, Nanjing 210002, China [7]Department of Endocrinology and Metabolism, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China [8]Department of Endocrinology and Metabolism,Zhongda Hospital Southeast University, Nanjing 210009, China [9]Department of Endocrinology and Metabolism, Nanjing First Hospital, Nanjing 210000, China [10]Department of Endocrinology and Metabolism, Nanjing Children's Hospital, Nanfing 210008, China [11]Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China [12]Department of Endocrinology and Metabolism, Nanjing Governmental Hospital, Nanjing 210008, China [13]Department of Endocrinology and Metabolism, Northern Jiangsu People's Hospital, Yangzhou 225001, China [14]Department of Endocrinology and Metabolism, Wuxi People's Hospital, Wuxi 214023, China [15]Department of Endocrinology and Metabolism, Jiangsu Jiangyin People's Hospital, Wuxi 214400, China [16]Department of Endocrinology and Metabolism, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221006, China [17]Department of Endocrinology and Metabolism, Xuzhou Central Hospital, Xuzhou 221009, China [18]Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, Suzhou 215006, China [19]Department of Endocrinology and Metabolism, The Second Affiliated Hospita

出　　处：《Science China(Life Sciences)》2016年第9期930-939,938-939+932-937,共10页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China(81270897,81300668,81370939,81400813,81400808,81530026,81370922);the Jiangsu Provincial Special Program of Medical Science(BL2012026);the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions support this study

摘　　要：Type 1 diabetes mellitus is heterogeneous in many facets. The patients suffered from type 1 diabetes present several levels of islet function as well as variable number and type of islet-specific autoantibodies. This study was to investigate prevalence and heterogeneity of the islet autoantibodies and clinical phenotypes of type 1 diabetes mellitus; and also discussed the process of islet failure and its risk factors in Chinese type 1 diabetic patients. A total of 1,291 type 1 diabetic patients were enrolled in this study. Demographic information was collected. Laboratory tests including mixed-meal tolerance test, human leukocyte antigen alleles, hemoglobin A1 c, lipids, thyroid function and islet autoantibodies were conducted. The frequency of islet-specific autoantibody in newly diagnosed T1 DM patients(duration shorter than half year) was 73% in East China. According to binary logistic regressions, autoantibody positivity, longer duration and lower Body Mass Index were the risk factors of islet failure. As the disease developed, autoantibodies against glutamic acid decarboxylase declined as well as the other two autoantibodies against zinc transporter 8 and islet antigen 2. The decrease of autoantibodies was positively correlated with aggressive beta cell destruction. Autoantibodies can facilitate the identification of classic T1 DM from other subtypes and predict the progression of islet failure. As there were obvious heterogeneity in autoantibodies and clinical manifestation in different phenotypes of the disease, we should take more factors into consideration when identifying type 1 diabetes mellitus.Type 1 diabetes mellitus is heterogeneous in many facets. The patients suffered from type 1 diabetes present several levels of islet function as well as variable number and type of islet-specific autoantibodies. This study was to investigate prevalence and heterogeneity of the islet autoantibodies and clinical phenotypes of type 1 diabetes mellitus; and also discussed the process of islet failure and its risk factors in Chinese type 1 diabetic patients. A total of 1,291 type 1 diabetic patients were enrolled in this study. Demographic information was collected. Laboratory tests including mixed-meal tolerance test, human leukocyte antigen alleles, hemoglobin A1 c, lipids, thyroid function and islet autoantibodies were conducted. The frequency of islet-specific autoantibody in newly diagnosed T1 DM patients（duration shorter than half year） was 73% in East China. According to binary logistic regressions, autoantibody positivity, longer duration and lower Body Mass Index were the risk factors of islet failure. As the disease developed, autoantibodies against glutamic acid decarboxylase declined as well as the other two autoantibodies against zinc transporter 8 and islet antigen 2. The decrease of autoantibodies was positively correlated with aggressive beta cell destruction. Autoantibodies can facilitate the identification of classic T1 DM from other subtypes and predict the progression of islet failure. As there were obvious heterogeneity in autoantibodies and clinical manifestation in different phenotypes of the disease, we should take more factors into consideration when identifying type 1 diabetes mellitus.

关 键 词：AUTOANTIBODIES HETEROGENEITY islet failure type 1 diabetes 

分 类 号：R587.1[医药卫生—内分泌]