谷氨酸脱羧酶抗体和胰岛细胞抗体联合检测对1型糖尿病早期诊断的意义

目的　对９８４ 例糖尿病患者的胰岛细胞抗体（ＩＣＡ） 、谷氨酸脱羧酶抗体（ＧＡＤＡ） 和血清Ｃ肽进行了检测与分析,了解ＩＣＡ 和ＧＡＤＡ 阳性率以及阳性患者的胰岛功能情况,以明确ＩＣＡ 和ＧＡＤＡ检测对１ 型糖尿病早期诊断的意义。方法　采用免疫组化法检测ＩＣＡ,ＥＬＩＳＡ 法定量检测ＧＡＤＡ, 放射免疫法检测血清空腹和餐后Ｃ 肽。结果　ＩＣＡ 和（或）ＧＡＤＡ 阳性（ 阳性组）１６８ 例（１７ ．０％ ） 高于ＩＣＡ 阳性率（１０．５ ％） 和ＧＡＤＡ 阳性率（１２．０ ％ ,Ｐ＜ ０ ．０５） 。成年患者ＧＡＤＡ 阳性率（１０ ．５％ ） 高于ＩＣＡ（７．７ ％ , Ｐ＜ ０ ．０５） , 青少年患者ＩＣＡ 阳性率（４６．５ ％） 高于ＧＡＤＡ（３１．０％ ,Ｐ＜０．０１）。抗体阳性患者的空腹和餐后Ｃ肽〔（３２５ ±３６８）ｐｍｏｌ／Ｌ和（７４５±７６７）ｐｍｏｌ／Ｌ〕明显低于抗体阴性患者〔（７０１ ±４３４）ｐｍｏｌ／Ｌ和（１ ６１４ ±９６７）ｐｍｏｌ／Ｌ,Ｐ＜０ ．００１〕。结论　自身抗体阳性患者的胰岛功能明显低于阴性患者,提示自身抗体阳性患者胰岛功能有明显损伤。在成年糖尿病患者中ＧＡＤＡ检测较ＩＣＡ 更为重要,而在青少年糖尿病患者中则ＩＣＡ阳性     

2型糖尿病患者血清GAD抗体的定量测定及相关因素分析

为了获得２型糖尿病患者谷氨酸脱羧酶（ＧＡＤ）抗体阳性标准及阳性率,我们对８１例２型糖尿病患者的血清ＧＡＤ抗体进行了定量测定,并对其相关因素进行了分析。现将结果报告如下。资料与方法：初诊２型糖尿病（符合１９８５年ＷＨＯ制订的诊断标准）患者８１例,男３６例,女４５例;年龄４９．０±１０．３岁;病程４．５±４．３年。采用放免法测定其空腹血清ＧＡＤ抗体;ＧＡＤ抗体放免试剂盒由法国ＣＩＳ公司提供。所有患者同时测量身高、体重,计算体重指数,并采用馒头餐进行Ｃ－肽释放试验,计算Ｃ－肽面积〔ｐｍｏｌ／（Ｌ·ｈ）…     

成人晚发自身免疫性糖尿病的特点及诊断要点探讨

为加强临床医师对成人晚发自身免疫性糖尿病（ＬＡＤＡ）的认识，本研究比较了ＬＡＤＡ２５例、胰岛素依赖型糖尿病５７例（儿童发病２１例、成人酮症发病３６例）、非胰岛素依赖型糖尿病３８例（轻至中度３０例、重度８例）及正常人４２例的临床、空腹血糖、血浆Ｃ肽水平及ＨＬＡ－ＤＱＡ１、－ＤＱＢ１链基因频率，提出ＬＡＤＡ的特点及诊断要点为：（１）２０～４８岁发病，发病时多饮、多尿、多食症状明显，体重下降快，体重指数（ＢＭＩ）≤２５，空腹血糖≥１６．５ｍｍｏｌ／Ｌ；（２）空腹血浆Ｃ肽≤０．４ｎｍｏｌ／Ｌ，早晨空腹１００ｇ馒头餐后１小时或（和）２小时Ｃ肽≤０．８ｎｍｏｌ／Ｌ；（３）谷氨酸脱羧酶抗体阳性；（４）ＨＬＡ－ＤＱＢ１链第５７位点为非天门冬氨酸纯合子基因（易感基因）。第（１）点是基本临床特点，加上第（２）、（３）、（４）点中任何一点就考虑诊断ＬＡＤＡ，尽早采用饮食、运动及胰岛素治疗，使空腹及三餐后血糖、糖化血红蛋白（ＨｂＡ１ｃ）控制到正常水平，以保护受自身免疫破坏的胰岛Ｂ细胞功能，有利于防止糖尿病眼、肾、神经并发症。     

谷氨酸脱羧酶抗体和胰岛细胞抗体联合检测对1型糖尿病？…

对９８４例糖尿病患者的胰岛细胞抗体、谷氨酸脱羧酶抗体和血清Ｃ肽进行了检测与分析了解ＩＣＡ和ＧＡＤＡ阳性率以及阳性患者的胰岛功能情况，以明确ＩＣＡ和ＧＡＤＡ检测对１型糖尿病早期诊断的意义。方法采用免疫组化法检测ＩＣＡ，ＥＬＩＳＡ法定量检测ＧＡＤＡ，放射免疫法检测血清空腹和餐后Ｃ肽。结果ＩＣＡ和（或）ＧＡＤＡ阳性（阳性组）１６８例（１７．０％）高于ＩＣＡ阳性率（１０．５％）和ＧＡＤＡ阳性率（１２．０％     

胰岛自身抗体对Ⅰ型糖尿病诊断效率的研究

目的 探讨免疫指标谷氨酸脱羧酶抗体（ＧＡＤ６５－Ａｂ）与胰岛细胞抗体（ＩＣＡ）对Ⅰ型糖尿病的诊断价值。方法 Ⅰ型糖尿病１０４例,正常对照１０２例,用放射配体分析法检测ＧＡＤ６５－Ａｂ,ＥＬＩＳＡ法检测ＩＣＡ;用受试者运筹特性（ＲＯＣ）曲线及曲线下面积比较二者的诊断效率。结果 （１）ＧＡＤ６５－Ａｂ最佳界值０．３０,ＩＣＡ最佳界值０．４５。ＧＡＤ６５－Ａｂ、ＩＣＡ、ＲＯＣ曲线下面积分别为０．８３５、     

糖尿病患者血清生长激素与肌酐清除率

测定了１６例胰岛素依赖型糖尿病（ＩＤＤＭ）患者，１９例非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者和２３例对照者的血清生长激素（ＧＨ）水平。在ＩＤＤＭ组，无论是肌酐清除率（Ｃｃｒ）正常或减低，其ＧＨ值均为２．５３±１．７３μｇ／Ｌ，均高于对照组的０．７１±０．５３μｇ／Ｌ（Ｐ＜０．０５），ＧＨ与Ｃｃｒ呈负相关（ｒ＝０．６３，Ｐ＜０．０１），ＮＩＤＤＭ组Ｃｃｒ＜５０ｍｌ／ｍｉｎ者ＧＨ值为１．８３±０．４７μｇ／Ｌ显著高于对照组（Ｐ＜０．０５）和Ｃｃｒ＞８０ｍｌ／ｍｉｎ组（ＧＨ０．８３±０．４９μｇ／Ｌ，Ｐ＜０．０５）。糖尿病（ＤＭ）伴微血管并发症者，ＧＨ值为２．９２±１．７０μｇ／Ｌ，高于无此并发症者ＧＨ１．２４±０．９７μｇ／Ｌ，（Ｐ＜０．０１），认为ＧＨ与ＤＭ微血管并发症有关。     

细胞分化剂对肿瘤细胞凋亡的诱导与耐药性的逆转

目的 搪塞细胞分化剂（ＣＤＡ－Ⅱ）诱导ＫＢＶ２００细胞凋亡与逆转其耐药性的关系。方法 用四唑蓝比色法检测细胞存活率，用形态学（光镜、透射电镜）、生化学「末端脱氧核苷酸转移标记法」、流式细胞术分析细胞凋亡。结果 ＣＤＡ－Ⅱ毒性作用很低。１ｇ／Ｌ和２ｇ／ＬＣＤＡ－Ⅱ可使长春新碱（ＶＣＲ）对ＫＢＶ２００半数抑制浓度由１０８７．７ｎｍｏｌ／Ｌ分别降低至４１６．０ｎｍｏｌ／Ｌｅｙ １８．５ｎｍｏｌ／Ｌ，２ｇ     

川芎嗪对冠心病患者脂质过氧化作用及血液流变学的影响

对４２例冠心病患者应用川芎嗪治疗前后的血清脂蛋白代谢、过氧化脂质、抗氧化酶活性及血液流变学进行了对照观察。结果表明：①血清ＴＧ、ＴＣ、（ＬＤＬ＋ＶＬＤＬ）－Ｃ值及ＴＣ／ＨＤＬ－Ｃ比值均明显降低（Ｐ〈０．０１，Ｐ〈０．０５），而ＨＤＬ－Ｃ则显著升高（Ｐ〈０．０５）；②ＭＤＡ水平显著降低（Ｐ〈０．０１），ＳＯＤ及ＧＡＴ活性明显提高（Ｐ〈０．０５，Ｐ〈０．０１）；③血浆粘度、红细胞压积和纤维蛋白原均降低     

老年男性Ⅱ型糖尿病患者血清性激素变化及与冠心病的关系

对≥６０岁的男性Ⅱ型糖尿病（Ⅱ－ＤＭ）患者及合并冠心病患者各５０例进行研究，测定其血清Ｔ、Ｅ２、血糖（ＧＬＵ）、ＴＣ、ＴＧ水平。结果：男性Ⅱ－ＤＭ及合并冠心病患者血清Ｔ低于健康对照组（Ｐ＜０．０５和Ｐ＜０．０１），血清Ｅ２也有下降趋势（Ｐ＞０．０５），Ｅ２／Ｔ比值则高于对照组（Ｐ＞０．０５）；相关分析显示Ｔ与ＧＬＵ、ＴＣ、ＴＧ均呈负相关（Ｐ＜０．０１），而Ｅ２则似乎与ＧＬＵ、ＴＣ、ＴＧ无明显相关性，ＧＬＵ与ＴＣ、ＴＧ呈正相关（Ｐ＜０．０１）。结论：Ⅱ－ＤＭ及冠心病患者均存在性激素改变，并与血糖、血酯一起构成影响糖尿病、冠心病的不利因素。     

糖尿病酮症酸中毒并肝损害临床分析

目的探讨导致糖尿病酮症（ＤＫ）及酮症酸中毒（ＤＫＡ）患者肝损害的相关因素．方法ＤＫ或ＤＫＡ患者９９例,其中ＡＬＴ及ＡＳＴ均异常升高１１例（Ａ组）,单项ＡＬＴ异常升高１３例（Ｂ组）,肝功能正常７５例（Ｃ组）,对以上各组患者的血二氧化碳结合力（ＣＯ２ＣＰ）、尿素氮（ＢＵＮ）、血糖（ＢＧ）和血浆渗透压（ＯＳＭ）进行了统计分析．结果Ａ,Ｂ两组患者的ＣＯ２ＣＰ明显低于Ｃ组（Ｐ＜００１,ｔ＝６３３和ｔ＝６４３）,而ＢＵＮ则明显升高（Ｐ＜００１,ｔ＝３６１,ＡｖｓＣ;Ｐ＜００１,ｔ＝４３５,ＢｖｓＣ）,Ａ组的ＢＧ（Ｐ＜００５,ｔ＝２８４）和血浆ＯＳＭ（Ｐ＜００５,ｔ＝３１０）水平也显著高于Ｃ组,而Ｂ组患者的ＢＧ及血浆ＯＳＭ与Ｃ组比较无差异;与Ｂ组相比,Ａ组患者的ＣＯ２ＣＰ明显降低（Ｐ＜００２,ｔ＝２７１）,ＢＧ（Ｐ＜００５,ｔ＝２８９）和血浆ＯＳＭ（Ｐ＜００５,ｔ＝２３６）明显升高．此外,Ⅰ型糖尿病患者血清转氨酶异常升高的发生率明显高于Ⅱ型糖尿病患者（Ｐ＜００５,χ２＝４３８）．结论酸中毒和脱水是导致糖尿病酮症及酮症酸中毒患者肝损害的重要因素,酸中毒及脱水程度与肝损害程度相关．     

蛋白酪氨酸磷酸酶抗体对成人隐匿性自身免疫性糖尿病的诊断价值

目的探讨蛋白酪氨酸磷酸酶抗体（IA-2A）对成人隐匿性自身免疫性糖尿病（LADA）的诊断价值。方法采用放射配体法检测2027例初诊2型糖尿病（T2DM）患者的IA．2A和谷氨酸脱羧酶抗体（GAD-Ab）,分析IA-2A在初诊T2DM患者中的分布及其与临床特征的关系。结果初诊T2DM患者中IA-2A阳性检出率低于GAD-Ab阳性检出率（2．2％7）S10．6％,P〈0．01）。联合GAD-Ab和IA-2A检测,可使LADA阳性检出率达11．5％。IAm2A在低体重、低c肽水平患者中阳性检出率高;随着起病年龄增大,IA-2A阳性检出率下降（P〈0．05）。与T2DM组比较,单独IA-2A阳性患者使用胰岛素治疗的比例高（P〈0．05）。高滴度IA-2A阳性LADA患者具有起病年龄小（P〈0．01）、体重轻、高血压比例低、空腹C肽低、合并GAD-Ab阳性和使用胰岛素比例高（P〈0．05）等特点。结论IA-2A检测对LA—DA具有辅助诊断价值,与GAnAb联合检测可提高LADA诊断的敏感性。     

羧基肽酶-H抗体对成人隐匿性自身免疫糖尿病的诊断意义

目的 探讨羧基肽酶—H自身抗体(CPH—Ab)阳性的2型糖尿病(T2DM)患者的临床特征及该抗体对成人隐匿性自身免疫糖尿病(LADA)的诊断价值。方法 选择临床初诊为T2DM患者545例，1型糖尿病(T1DM)患者85例，健康对照123例进行CPH—Ab测定，同时检测T2DM患者谷氨酸脱羧酶抗体(GAD—Ab)。比较各组CPH—Ab的阳性率以及T2DM中依据CPH—Ab、GAD—Ab划分的3组患者的临床特点。采用放射免疫沉淀法检测CPH—Ab和GAD—Ab。结果 CPH—Ab阳性率在T2DM患者(5．5％，30／545)高于T1DM患者(0％，0／85)和正常对照(0．8％，1／123)(P＜0．05)，30例CPH—Ab阳性的T2DM患者只有1例同时GAD—Ab阳性。CPH—Ab在低体重(BMI＜21kg／m^2)者中的阳性率较高，且该抗体阳性的患者具有起病年龄跨度大、病程较长、低体重、易发生酮症等特点，其空腹C肽介于GAD—Ab阳性与两种抗体(GAD—Ab和CPH—Ab)均阴性的T2DM患者之间，反映代谢综合征的指标水平较低(包括较低的BMI、血压和甘油三酯)，而周围神经病变的比例较高。结论 CPH—Ab阳性糖尿病患者的临床特点介于经典的LADA(GAD—Ab阳性)与T2DM患者间。CPH抗体检测是LADA诊断的一项新指标。     

Six-year follow-up of pancreatic β cell function in adults with latent autoimmune diabetes

AIM: To investigate the characteristics of the progression of islet β cell function in Chinese latent autoimmune diabetes in adult (LADA) patients with glutamic acid decarboxylase antibody (GAD-Ab) positivity, and to explore the prognostic factors for β cell function. METHODS: Forty-five LADA patients with GAD-Ab positivity screened from phenotypic type 2 diabetic (T2DM) patients and 45 T2DM patients without GAD-Ab matched as controls were followed-up every 6 mo. Sixteen patients in LADA1 and T2DM1 groups respectively have been followed-up for 6 years, while 29 patients in LADA2 and T2DM2 groups respectively for only 1.5 years. GAD-Ab was determined by radioligand assay, and C-peptides (CP) by radioimmune assay. RESULTS: The percentage of patients whose fasting CP(FCP) decreased more than 50% compared with the baseline reached to 25.0% at 1.5th year in LADA1 group, and FCP level decreased (395.8±713 vs 572.8±72.3 pmol/L, P<0.05) at 2.5th year and continuously went down to the end of follow-up. No significant changes of the above parameters were found in T2DM1 group. The average decreased percentages of FCP per year in LADA and T2DM patients were 15.8% (4.0-91.0%) and 5.2% (-3.5 to 35.5%, P=0.000) respectively. The index of GAD-Ab was negatively correlated with the FCP in LADA patients (rs = -0.483, P = 0.000). The decreased percentage of FCP per year in LADA patients were correlated with GAD-Ab index, body mass index (BMI) and age at onset (rs = 0.408, -0.301 and -0.523 respectively, P<0.05). Moreover, GAD-Ab was the only risk factor for predicting 13 cell failure in LADA patients (B = 1.455, EXP (B) = 4,283, P = 0.023). CONCLUSION: The decreasing rate of islet 13 cell function in LADA, being highly heterogeneous, is three times that of T2DM patients. The titer of GAD-Ab is an important predictor for the progression of islet 13 cell function, and age at onset and BMI could also act as the predictors.     

磺脲类降糖药继发失效患者中成人隐匿性自身免疫糖尿病的患病率调查

目的　探讨磺脲类降糖药继发失效 (SF)患者中成人隐匿性自身免疫糖尿病 (LADA)的患病率及其临床特点。　方法　在SF组 (n =2 38)中筛查谷氨酸脱羧酶抗体 (GAD Ab)和胰岛细胞抗体 (ICA) ,并将之与非继发失效 (NSF)组 (n =110 )中的阳性率比较。　结果　SF组中GAD Ab阳性的LADA的患病率为 13.9%( 33 2 38) ,NSF组为 10 .0 %( 11 110 ) ,两组差异无显著意义 (P >0 .0 5 )。LADA患者体重指数低于GAD Ab阴性者 (P <0 .0 1) ,发病年龄、血压、甘油三酯、C肽值均降低 (P <0 .0 5 )。联合检测GAD Ab和ICA ,SF组中LADA的患病率可达 2 2 .7%( 5 4 2 38) ,NSF中为 18.1%( 2 0 110 ) ,SF组与NSF组LADA患病率高于单独以GAD Ab检测 (P <0 .0 1)。　结论　SF的糖尿病患者中LADA的患病率较高。联合检测GAD Ab和ICA可提高LADA诊断的敏感性。     

Islet cell and glutamic acid decarboxylase antibodies in hyperthyroid patients: at diagnosis and following treatment

Objectives. To study the frequency of islet cell (ICA) and glutamic acid decarboxylase (GAD-Ab) antibodies in patients with hyperthyroidism of different types at diagnosis before treatment and in the euthyroid state following treatment. Setting. Department of Endocrinology, Malmö University Hospital, Malmö, Sweden. Subjects and design. Blood samples were collected at diagnosis from 129 hyperthyroid patients, and about 6 months later, from 78 of the patients (euthyroid state). Ninety-two patients had Graves' disease (69 females and 23 males, median age 49 years, range 17–85 years), and 37 patients had toxic nodular goitre/solitary toxic adenoma (34 females and three males, median age 69 years, range 24–86 years). Interventions. Most patients were treated by radioactive iodine following the first blood sample. Main outcome measures. ICA and GAD-Ab in serum. Results. At diagnosis of Graves' disease, ICA were detected in two out of 92 (2.2%) patients, two out of 85 (2.4%) without diabetes mellitus and in the euthyroid state in one patient. None of the patients with toxic nodular goitre/solitary toxic adenoma had detectable ICA. At diagnosis of Graves' disease, GAD65-Ab as well as GAD67-Ab were detected in 11 out of 85 (13%) patients without diabetes. As many as six out of 11 GAD67-Ab-positive patients were GAD65-Ab negative. In the euthyroid state, GAD65-Ab were found in six out of 51 (12%) and GAD67-Ab in eight out of 51 (16%) of the non-diabetic Graves' disease patients. The frequencies of GAD65-Ab and GAD67-Ab in toxic nodular goitre/solitary toxic adenoma, diabetes excluded, were 3 and 0%, respectively, in the hyperthyroid state. Conclusion . The frequency of ICA in patients with hyperthyroidism is not increased as compared to the background population. GAD-Ab seems to be associated with Graves' disease and not with hyperthyroidism. The presence of GAD67-Ab in GAD65-Ab negative sera from patients with Graves' disease indicates autoreactivity against a specific GAD67 epitope.     

Six-year follow-up of pancreatic β cell function in adults with latent autoimmune diabetes

AIM: To investigate the characteristics of the progression of islet β cell function in Chinese latent autoimmune diabetes in adult (LADA) patients with glutamic acid decarboxylase antibody (GAD-Ab) positivity, and to explore the prognostic factors for β cell function. METHODS: Forty-five LADA patients with GAD-Ab positivity screened from phenotypic type 2 diabetic (T2DM) patients and 45 T2DM patients without GAD-Ab matched as controls were followed-up every 6 mo. Sixteen patients in LADA1 and T2DM1 groups respectively have been followed-up for 6 years, while 29 patients in LADA2 and T2DM2 groups respectively for only 1.5 years. GAD-Ab was determined by radioligand assay, and C-peptides (CP) by radioimmune assay.RESULTS: The percentage of patients whose fasting CP(FCP) decreased more than 50% compared with thebaseline reached to 25.0% at 1.5th year in LADA1 group, and FCP level decreased (395.8±71.5 vs 572.8±72.3 pmol/L, P＜0.05) at 2.5th year and continuously went down to the end of follow-up. No significant changes of the above parameters were found in T2DM1 group. The average decreased percentages of FCP per year in LADA and T2DM patients were 15.8% (4.0-91.0%) and 5.2% (-3.5 to 35.5%, P= 0.000) respectively. The index of GAD-Ab was negatively correlated with the FCP in LADA patients (rs= -0.483, P = 0.000). The decreased percentage of FCP per year in LADA patients were correlated with GAD-Ab index, body mass index (BMI) and age at onset (rs = 0.408, -0.301 and -0.523 respectively, P＜0.05). Moreover, GAD-Ab wasthe only risk factor for predicting βcell failure in LADA patients (B = 1.455, EXP (B) = 4.283, P = 0.023). CONCLUSION: The decreasing rate of islet β cell function in LADA, being highly heterogeneous, is three times that of T2DM patients. The titer of GAD-Ab is an important predictor for the progression of islet β cell function, and age at onset and BMI could also act as the predictors.     

Immunologic and genetic aspects of latent autoimmune diabetes in the adult

The presence of islet cell autoantibodies (ICA), and especially of glutamic acid decarboxylase autoantibodies (GAD65Ab), in patients with non-insulin-dependent diabetes mellitus identifies the so-called latent autoimmune diabetes in the adult (LADA). LADA patients have an increased risk for developing insulin deficiency, and in 60-80% of cases the exogenous insulin therapy must be started within 5-6 years. GAD65Ab identify a subgroup of type 2 diabetic (T2DM) patients with low body mass index (BMI) at the time of diagnosis. The presence of GAD65Ab at high titres and directed against COOH-terminal epitopes of the autoantigen, or the presence of both GAD65Ab and ICA, discriminates patients with clinical characteristics very similar to those of a slowly progressive form of type 1 diabetes (T1DM). On the other hand, the presence of low levels GAD65Ab, in the absence of ICA or other immune markers, such as IA-2 antibodies, characterizes a subgroup of patients with clinical characteristics almost indistinguishable from those of typical T2DM patients. The autoimmune origin of LADA is also demonstrated by the increased frequency of thyroid and adrenal autoantibodies, as compared to GAD65Ab-negative T2DM patients, and by the strong genetic association with HLA-DR3-DQ2, -DR4-DQ8 and the polymorphisms of the MHC class I chain-related A (MICA) and CTLA-4 genes. Metabolic studies have shown the coexistence of insulin resistance and insulin secretion defect supporting the hypothesis that LADA may be the result of the interaction of a genetic background predisposing for islet autoimmunity and a genetic background predisposing for T2DM.     

Epitope analysis of GAD65 autoantibodies in adult-onset type 1 diabetes and latent autoimmune diabetes in adults with thyroid autoimmunity

This study aimed at determining which GAD65 epitopes the spontaneous antibodies recognized and whether the epitope-specific GAD65Abs could be associated with the development of thyroid autoimmunity in Chinese adult-onset type 1 diabetes (T1DM) and latent autoimmune diabetes in adults (LADA). The levels of GAD65Abs and their reactivities to N-terminal (GAD65-N), middle (GAD65-M) and C-terminal (GAD65-C) regions of human GAD65 were measured by radioligand assay in 109 patients with adult-onset T1DM and 107 with LADA. TPOAb, TGAb and the genotypes of HLADQA1-DQB1 were determined. The percentage of LADA patients with GAD65-NAb was significantly higher than that of adult-onset T1DM patients (21.5% vs. 11.0%, P = 0.037), but LADA patients with GAD65-CAb less than T1DM patients (47.7% vs. 70.6%, P = 0.001). LADA patients with both GAD65-M and GAD65-CAb (GAD65-M + CAb) appeared to be at higher risk for the development of thyroid autoimmunity, lower serum C-peptide level and the requirement for insulin therapy (P < 0.05). More frequent T1DM patients with HLADQA1*03-DQB1*0303 developed GAD65-M + CAb (55.8% vs. 35.1%, P = 0.008). In comparison with those without thyroid autoimmunity, more frequent T1DM patients and LADA patients with thyroid autoimmunity displayed GAD65-M + CAbs (44.0% vs.16.9% and 53.1% vs. 17.3%, P = 0.002 and <0.001, respectively) with a diagnostic specificity of 83.1 or 82.7% for thyroid autoimmunity, respectively. LADA patients with GAD65-M + CAbs had clinical features similar to T1DM patients. Adult-onset T1DM and LADA patients with GAD65-M + CAbs are at an increased risk for the development of thyroid autoimmunity.     

LADA患者外周血单个核细胞对胰岛素和谷氨酸脱羧酶的增殖反应

目的探讨成人隐匿性自身免疫糖尿病(LADA)患者外周血单个核细胞(PBMC)对胰岛素和谷氨酸脱羧酶(GAD)的增殖反应。方法密度梯度离心法分离21例LADA、25例2型糖尿病(DM)及20名正常对照PBMC,3HTdR掺入法检测其对胰岛素和GAD及其分别联合白细胞介素2(IL2)刺激的增殖反应,以刺激指数(SI)反映增殖反应强度。结果(1)PBMC对PHA、胰岛素或GAD刺激的增殖反应在LADA、2型DM和正常对照组间差异无统计学意义。(2)对于胰岛素或GAD联合IL2(胰岛素 IL2,GAD IL2)刺激,LADA组SI高于2型DM组(5.1vs0.8;;7.0vs0.8,均P<0.05);;胰岛素 IL2刺激较胰岛素或IL2单独刺激的倍增值,GAD IL2刺激较GAD或IL2单独刺激的倍增值LADA组高于2型DM组(4.0vs1.0;;3.4vs0.3;;6.3vs1.2;;4.6vs0.3,均P<0.05)。(3)LADA患者胰岛素刺激的SI胰岛素与GAD抗体指数呈负相关。结论LADA患者体内存在已致敏的T细胞,其活化效应在特异性抗原(GAD或胰岛素)和IL2共刺激时方可被发现。