【作者】 杨非柯； 黄干； 侯粲； 周智广；

【Author】 YANG fei-ke;HUANG gan;HOU can;Zhou Zhi-guang;Insititue of Metabolism and Endocrinology,Diabetes Center,the Second Xiangya Hospital,Central South University;

【机构】 中南大学湘雅二医院代谢内分泌科； 中南大学糖尿病中心； 中南大学代谢综合征研究中心； 长沙市中心医院老干科；

【摘要】 目的:研究蛋白酪氨酸磷酸酶抗体(IA2-Ab)在初诊2型糖尿病(T2DM)患者中的阳性检出率及其分布特点,探讨IA2-Ab对成人隐匿性自身免疫糖尿病(LADA)患者的诊断价值及IA2-Ab阳性LADA患者的临床特征。方法:选择2027例(年龄>15岁)初诊T2DM患者,用放射配体法检测IA2-Ab和谷氨酸脱羧酶抗体(GAD-Ab),分析IA2-Ab在初诊T2DM患者中的分布特点及其与临床特征的关系。以筛查出的IA2-Ab阳性患者为病例组,以GAD-Ab阳性患者和两种抗体均阴性患者为对照组,比较不同胰岛自身抗体状态LADA患者的临床特征。比较不同抗体滴度的IA2-Ab阳性LADA患者的临床特征。分析IA2-Ab对LADA患者胰岛β细胞功能的影响。结果:(1)初诊T2DM患者中IA2-Ab的阳性检出率为2.2%(44/2027),与UKPDS对高加索人的研究结果一致(2.2%vs 2.2%),低于日本、印度的研究结果。IA2-Ab的阳性检出率显著低于GAD-Ab的阳性检出率(10.6%,214/2027例)(P<0.001)。且在高滴度GAD-Ab组中IA-2Ab的阳性检出率高(P<0.01)。在已检测GAD-Ab基础上加测IA2-Ab,可提高LADA阳性检出率1.1%。(2)IA2-Ab在初诊T2DM患者中的分布峰值处于起病年龄25~34岁组,且抗体阳性的检出率随着起病年龄增大而下降。IA2-Ab在低体重(BMI≤21 kg/m2)、低C肽(FCP<300 pmol/L)患者中阳性检出率高(P<0.05);不伴代谢综合征的糖尿病患者IA-2Ab的阳性检出率高于伴代谢综合征的糖尿病患者(2.4%vs 1.9%,P<0.001)。(3)单独IA-2Ab阳性患者的临床表现多样,C肽水平与抗体阴性患者间差异无显著性(P>0.05),其他临床特征与T2DM患者间的差异小。而IA2-Ab合并GAD-Ab阳性LADA患者具有起病年龄小,低体重,胰岛功能差,使用胰岛素治疗的比例高和伴代谢综合征比例低等特点。(4)高滴度的IA2-Ab阳性LADA患者具有以下特点:起病年龄小、病程短、体重指数低、空腹C肽值低,合并高血压病和代谢综合征的比例低,而合并GAD-Ab阳性和使用胰岛素治疗的比例高。结论:(1)单用IA-2Ab筛选诊断LADA的效率较低,联合两种抗体检测可在一定程度上提高LADA诊断的敏感性;(2)IA2-Ab倾向于出现在低龄、低体重指数的患者。(3)单独IA2-Ab阳性LADA患者临床表现多样,更接近T2DM患者。(4)高滴度IA2-Ab阳性LADA患者临床特征更接近1型糖尿病。更多还原

【Abstract】 Objective:To explore the diagnostic value of protein tyrosine phosphatase antibody(IA-2Ab) on Latent Autoimmune Diabetes in Adults(LADA) and to investigate the clinical features of IA2-Ab positive LADA patients.Methods:Radioligand assay was used to detect IA-2Ab and glutamic acid decarboxylase antibody(GAD-Ab) in 2,027 patients with newly diagnosed type 2 diabetes mellitus(T2DM)(age> 15 years old).Analysis on the distribution and the relationship of IA2-Ab with clinical features in the patients with newly diagnosed T2 DM.Results:(1) The positive rate of IA2-Ab in the patients with newly diagnosed T2 DM was 2.2%(44/2027).Detection of IA2-Ab on the basis of GAD-Ab can increase the positive rate of LADA by 1.1%.(2) The peak distribution rate of IA2-Ab was in the 25 to 34-year-old age group in the patients with newly diagnosed T2 DM.The positive detection rate of antibody declined with the increasing of onset age.The positive rate of IA2-Ab was high in the low birth weight(BMI < 21kg/m2),low C-peptide(FCP <300 pmol / L) group(P <0.05).(3) The clinical manifestations of individual IA-2Ab positive patients were diverse.Compared with the antibody-negative patients,there was no significant difference of C-peptide levels(P> 0.05).The differences of clinical features between single IA-2Ab positive patients and T2 DM were small.(4) The characteristics of hightiter IA2-Ab positive LADA patients were as the followingS:small onset age,short-duration,low body mass index,low fasting C-peptide values,low proportion of complicated with hypertension and metabolic syndrome,and high proportion of combining with the merger of GAD-Ab and insulin therapy.Conclusion:(1) Screening LADA by detection of IA-2Ab alone was less efficient,combining two antibody testing can improve the sensitivity for diagnosing LADA.(2) IA2-Ab tended to appear in the younger age,lower BMI patients.(3) The clinical manifestations of IA2-Ab positive LADA patients were diverse,and more inclined to T2 DM patients.(4) The clinical features of high titer IA2-Ab positive LADA patients were closer with type 1diabetes.更多还原