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目的 研究锌转运体8自身抗体(ZnT8A)和蛋白酪氨酸磷酸酶自身抗体(IA-2A)阳性的成人隐匿性自身免疫糖尿病(LA DA)患者胰岛功能的变化特点,为LADA的早期干预提供依据.方法 选择2005至2010年在我院就诊的初诊谷氨酸脱羧酶抗体(GADA)+ ZnT8A双阳性的LADA患者13例(GADA+ ZnT8A双阳性组),GADA+ IA-2A双阳性的LADA患者14例(GADA+ IA-2A双阳性组),GADA单独阳性的LADA患者42例(GADA单独阳性组),并选择同期抗体阴性的2型糖尿病(T2DM)患者40例作为对照组.对各组患者每年随访1次,连续随访3年,检测并比较各组患者基线和随访期间空腹血糖(FBG)、糖化血红蛋白(HbAl c)、空腹和餐后2hC肽(FCP、2 h CP)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平等临床指标的变化情况.本研究经中南大学湘雅二医院伦理委员会批准[(2006)伦审第(S05)号].结果 GADA+ IA-2A双阳性组FBG和HbAlc均高于GADA单独阳性组[(10.5±3.6) mmol/L、(9.3±2.6)％比(9.2±2.0) mmol/L、(7.4±2.0)％,P=0.017,0.011]和对照组[(10.5±3.6) mmol/L、(9.3±2.6)％比(8.5±1.2) mmol/L、(7.2±2.1)％,P=0.007,0.013],而FCP水平为415(68 ～934)pmol/L,低于GADA单独阳性组[538(224 ～1 146) pmol/L]以及对照组[643(163～l 658)pmol/L],P=0.015,0.003.GADA+ ZnT8A双阳性组、GADA+IA-2A双阳性组和GADA单独阳性组的空腹C肽水平均呈逐年下降趋势.GADA+ ZnT8A双阳性组和GADA+ IA-2A双阳性组空腹C肽水平年平均下降率为14.2％和12.4％,高于GADA单独阳性组和对照组的7.9％和0(均P＜0.01).结论 GADA合并IA-2A阳性的LADA患者初诊时胰岛功能较差,且ZnT8A和IA-2A均能加速LADA患者随病程延长而出现的胰岛功能衰竭.

Objective To observe the changes of islet function in ZnT8A positive and IA-2A positive patients so as to provide rationales for early intervention of LADA patients.Methods A total of 69 outpatients and inpatients with newly diagnosed LADA testing for GADA,IA-2A and ZnT8A by radioligand binding assay (RBA) were enrolled from 2005 to 2010,including 13 with double positive for GADA and ZnT8A (GADA + ZnT8A double positive group),14 with double positive for GADA and IA-2A (GADA + IA-2A double positive group) and 42 with positive for GADA alone (GADA positive group),40 type 2 diabetes mellitus (T2DM) patients negative for the above three autoantibodies were selected as control subjects (T2DM group).The baseline clinical data of all groups were compared and all patients were followed annually for 3 years.Fasting plasma glucose (FBG),HbA1 c,fasting C-peptide (FCP),C-peptide 2 h after meal (2 h CP),triglyceride (TG),total cholesterol (TC),high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were detected and compared among the above groups during the follow-ups.Results Compared to GADA positive group and T2DM group,the GADA + IA-2A double positive group had higher level of baseline FBG and HbA1c ((10.5 ± 3.6) mmol/L and (9.3±2.6)％ vs (9.2±2.0) mmol/L and(7.4±2.0)％,P=0.017,0.011) and had lower level of baseline FCP (415(68-934) vs 538(224-1 146)and 643(163-1 658)pmol/L,P =0.015,0.003).During the follow-ups,FCP decreased year-on-year in GADA + ZnT8A double positive,GADA + IA-2A double positive and GADA positive groups.The annual average rate of decrease in FCP was more rapid in GADA + ZnT8A double positive and GADA + IA-2A double positive groups than those in GADA positive alone and T2DM groups (all P ＜ 0.01).Conclusions The islet functions of newly diagnosed LADA patients with GADA and IA-2A positive are much worse.And emergence of ZnT8A and IA-2A may accelerate the failure of islet function with diabetic progress in LADA patients.