谷氨酸脱羧酶抗体的临床意义

谷氨酸脱羧酶（ＧＡＤ）抗体在Ⅰ型糖尿病不同的发病阶段均可持续高水平存在。与ＩＣＡ和ＩＡＡ相比，ＧＡＤ抗体与成人晚发自身免疫性糖尿病（ＬＡＤＡ）关系更密切，在检出成人晚发自身免疫性糖尿病时价值更大。糖尿病发病时ＧＡＤ抗体的状态是预测其临床过程的理想指标，它可以将ＬＡＤＡ与Ⅱ型糖尿病区别开来，为正确分型提供确切的指标，从而更好地指导治疗。ＧＡＤ抗体检测作为理想工具适用于大规模人群中Ⅰ型糖尿病高危人群的筛查     

谷氨酸脱羧酶抗体的临床意义

谷氨酸脱羧酶（ＧＡＤ）抗体在Ⅰ型糖尿病不同的发病阶段均可持续高水平存在。在ＩＣＡ和ＩＡＡ相比，ＧＡＤ抗体与在人晚发自身免疫性糖尿病（ＬＡＤＡ）关系更密切，在检出成人晚发自身免疫性糖尿病时价值更大。糖尿病发病时ＧＡＤ抗体的状态是预测其临床过程的指标，它可以将ＬＡＤＡ与Ⅱ型糖尿病区别开来，为正确分型提供确切的指标，从而更好地指导治疗。ＧＡＤ抗体检测作为理想工具适用于大规模人群Ⅰ型糖尿病高危人群的筛查。     

成人隐匿性自身免疫性糖尿病的临床特点和诊断要点

目的 探讨ＬＡＤＡ的临床及诊断要点。方法 观察ＬＡＤＡ、成人１型ＤＭ、重症２型ＤＭ的临床、血糖、Ｃ肽水平、ＧＡＤＡｂ、ＩＣＡ等。结果 ＬＡＤＡ组自发性酮症１０例,ＧＡＤＡｂ阳性率１００％,高于ＩＣＡ。结果 ＬＡＤＡ的诊断依据主要是：（１）成人以２型ＤＭ起病方式发病和治疗,β细胞功能逐渐衰退,最终需胰岛治疗;（２）ＧＡＤＡｂ、ＩＣＡ阳性。     

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     

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、     

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）…     

谷氨酸脱羧酶抗体诊断成人隐匿性自身免疫性糖尿病探讨

采用放射配体法检测谷氨酸脱羧酶（ＧＡＤ６５）抗体，对１９５例≥３５岁非酮症Ⅱ型糖尿病起病半年以上者和４５例正常对照者的观察表明：本组Ⅱ型糖尿病者ＧＡＤ６５抗体阳性率为１４．８％，高于正常对照者的２．２％；发病年龄〈４０岁、有酮症史、体重指数（ＢＭＩ）〈２１ｋｇ／ｍ＾２、空腹血清Ｃ肽〈０．３ｎｍｏｌ／Ｌ和（或）胰升糖素刺激后６分钟血清Ｃ肽〈０．６ｎｍｏｌ／Ｌ者，ＧＡＤ６５抗体阳性率均高于相应对照组（     

成人晚发1型糖尿病相关抗体检测意义

将３２５例成人晚发１型糖尿病患者分成胰岛素（ＬＮＳ）分泌缺乏及非ＩＮＳ分泌缺乏两组,用间接酶联免疫吸附（ＥＬＩＳＡ）法测定其县岛细胞坑体（ＩＣＡ）、胰岛素抗体（ＩＡＡ）及谷氨酸脱羧酶抗体（ＧＡＤ－Ａｂ）,比较其相关性。结果两组ＩＣＡ、ＧＡＤ、Ａｂ阳性率、酮症发生率及体重指数有显著性差异。证明ＩＣＡ、ＧＡＤ－Ａｂ可作为成人晚发１型糖尿病的早期筛选指标。     

迟发性自身免疫性糖尿病患者血管紧张素Ⅰ转换酶基因多态性与其慢性合并症的关联研究

迟发性自身免疫性糖尿病 (ＬＡＤＡ)患者病情虽缓慢进展 ,仍然发生糖尿病微血管病变。本研究试图探讨ＬＡＤＡ患者血管紧张素转换酶 (ＡＣＥ)基因多态性与其慢性合并症关系。一、对象和方法1.研究对象 :ＬＡＤＡ组 :共 5 0例 (男 36 ,女 14) ,所有患者选择谷氨酸脱羧酶 (ＧＡＤ)和 (或 )胰岛细胞抗体 (ＩＣＡ)阳性者(3个月复查仍为阳性 ) ,初次发生酮症或酮症酸中毒的时间均为 6个月以上 ,排除速发 1型糖尿病。ｍｔＲＮＡＡ32 43Ｇ检查排除线粒体糖尿病。根据ＡＣＥ基因型不同分 3组 ,一般资料 (表 1)。糖尿病肾病根据连续 2次 2 4小时尿白…     

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。     

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.     

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。     

新诊断2型糖尿病患者谷氨酸脱羧酶抗体、胰岛细胞抗体和胰岛素自身抗体联合筛查成人隐匿性自身免疫性糖尿病的意义

目的 研究新诊断T2DM患者中LADA的检出率,并分析其临床特征. 方法 测定152例病程＜1年,且非酮症起病的新诊断T2DM患者GADA、ICA、IAA、血压、身高、体重及BMI,同时检测血脂、FPG、胰岛素、C-P、HbA1c、促甲状腺激素（TSH）、甲状腺球蛋白抗体（TG-Ab）和甲状腺过氧化物酶抗体（TPOAb）水平.观察LADA患者与T2DM患者临床特征与生化特征的差异. 结果 新诊断T2DM患者中LADA的检出率为7.89％;与自身抗体阴性组相比,自身抗体阳性组BMI、TC降低,胰岛素及C-P水平较低,嗜中性粒细胞计数TSH异常检出率与TPO阳性率增高（P＜0.05）. 结论 新诊断T2DM患者中存在一定比例的LADA患者;对于BMI较低、胰岛功能较差的新诊断T2DM患者应尽早测定GADA、ICA和IAA.LADA患者可能具有更高的免疫炎症因子表达及更低的TC水平.     

Insulin autoantibody could help to screen latent autoimmune diabetes in adults in phenotypic type 2 diabetes mellitus in Chinese

Latent autoimmune diabetes in adults (LADA) is characterized by a relatively mild diabetes onset, autoantibody positivity, and eventual requirement for insulin therapy. Glutamic acid decarboxylase autoantibodies (GADA) or cytoplasmic islet cell autoantibodies (ICA) play a key role in distinguishing LADA from type 2 diabetes mellitus (T2DM) in clinical practice. The aim of our research was to determine whether insulin autoantibody (IAA) has some additional value in diagnosing LADA. We analyzed IAA, GADA, and IA-2A (antibodies to insulinoma-associated antigen-2) in 1,003 newly diagnosed phenotypic T2DM patients, 110 type 1 diabetes mellitus (T1DM) patients, and 317 normal controls to survey the prevalence of IAA in phenotypic T2DM patients and the overlapping positivity of IAA with other autoantibodies. Sera were drawn within 7?days from the start of insulin therapy. Results showed that 3.39% of the newly diagnosed phenotypic T2DM, 0.95% of normal control (χ²?=?5.3, P?<?0.05), and 21.82% of T1DM (χ²?=?68.2, P?<?0.001) were positive for IAA at diagnosis. The combination frequency of three antibodies was 10.47%, which was higher than any single antibody testing. Combination testing of IAA with GADA and IA-2A could improve LADA diagnose rate by 2.39% than that of GADA and IA-2A. IAA-positive subjects had diabetes family history more common compared to its matched group (67.6% vs. 14.7%, P?=?0.000). Postprandial C-peptide in IAA-positive group tended to be lower, but the difference was not statistically significant (P?=?0.084). We concluded that IAA can be used to screen LADA in phenotypic T2DM in the Chinese population.     

Clinical, biochemical, and immunological characteristics of newly diagnosed nonobese diabetic patients aged 18-45 years in China

BackgroundThe purpose was to characterize the clinical, biochemical, and immunological features of newly diagnosed adult-onset nonobese diabetic patients in China.MethodsNewly diagnosed diabetic patients aged 18–45 years with body mass index<23 kg/m² were included. Excluding one mitochondrial diabetes patient, there were 102 diabetic patients enrolled in this study. Clinical and biochemical data were collected and analyzed. Radioimmunoassay was used to detect islet autoantibodies.ResultsAmong the 102 study participants, 68.6% had type 1 diabetes (T1DM), 20.6% had type 2 diabetes (T2DM), and 10.8% had latent autoimmune diabetes in adults (LADA). About 92% of the T1DM patients presented hyperglycemic symptoms. The corresponding number in T2DM and LADA patients was 13% and 38%, respectively (P<.01). C-peptide in T2DM patients (1.4±0.7 ng/ml) was significantly higher than that in T1DM (0.4±0.3 ng/ml) and LADA (0.4±0.2 ng/ml) patients (P<.01). The prevalence of glutamic acid decarboxylase antibody (GADA) (64.3%) in T1DM patients was higher than that of insulin autoantibody (17.1%) (P<.05). GADA and islet cell antibody (ICA) combination was positive in 75.7% of T1DM patients.ConclusionT1DM patients accounted for majority of the study sample. In addition, the clinical symptoms of T1DM patients were more severe compared with T2DM patients. GADA is the most sensitive autoantibody marker for adult-onset T1DM and LADA. GADA and ICA are the best test combination for adult-onset autoimmune diabetes. Specific types of diabetes should be in mind when diabetes presents itself with special transmission mode or with other extrapancreatic manifestations.     

Equivalent insulin resistance in latent autoimmune diabetes in adults (LADA) and type 2 diabetic patients

Insulin resistance is a primary component in the pathophysiology of type 2 diabetes. In latent autoimmune diabetes in adults (LADA), insulin resistance has been reported to be significantly lower than in autoantibody-negative type 2 diabetes (T2DM), but whether this might be related to differences in body mass index (BMI) has not been excluded. Furthermore, previous studies have used limiting inclusive criteria for LADA, requiring only the presence of GADA or IA-2A. To apply more inclusive criteria for LADA, consistent with recent recommendations, we defined LADA by clinical manifestations characteristic of T2DM, but with the presence of any combination of GADA, IA-2A, ICA, or IAA. We recruited 43 LADA patients, 70 T2DM patients, and 150 non-diabetic controls. Insulin resistance was assessed by both the homeostasis model assessment and the quantitative insulin sensitivity check index, and BMI was calculated. We found that insulin resistance in LADA is equivalent to that of T2DM. When insulin resistance is assessed as a function of BMI, both diabetic populations demonstrated an insulin resistance equally greater than normal controls. The interaction between insulin resistance and BMI in the two diabetic groups was significantly different from that demonstrated in non-diabetic controls. In summary, LADA demonstrates insulin resistance of similar magnitude to T2DM, but with the concurrent component of an immune attack against the pancreatic beta-cells. LADA patients may be at significant risk for metabolic consequences of insulin resistance other than glucose metabolism, such as those described in the metabolic syndrome. As complications and treatment regimens specific to LADA are realized, improved means of identification of LADA will become increasingly important.     

Role of anti-GAD,anti-IA2 antibodies and C-peptide in differentiating latent autoimmune diabetes in adults from type 2 diabetes mellitus

Latent autoimmune diabetes in adults (LADA) is a form of autoimmune diabetes affecting adult patients who do not require insulin at diagnosis, positive for circulating islet autoantibodies and characterized by slower beta cell destruction. The study was aimed to identify and characterize LADA patients from clinically diagnosed type 2 diabetes mellitus (DM). We estimated anti-glutamic acid decarboxylase (anti-GAD), anti-tyrosine phosphatase-like insulinoma antigen 2 (anti-IA2) antibodies, fasting connecting peptide (C-peptide) and other clinical and biochemical parameters in 297 clinically diagnosed type 2 DM patients. The diagnosis of LADA was made by the presence of at least one pancreatic autoantibody, and thereafter LADA groups were compared with those of autoantibody-negative type 2 DM groups. The prevalence of LADA was found to be 15.2 % among patients presumed to have type 2 DM. There was significant difference concerning age of patients (p?<?0.001), body mass index (p?<?0.001), serum levels of C-peptide (p?<?0.001), insulin (p?<?0.001), total cholesterol (p?<?0.001), triglycerides (p?=?0.025), high-density lipoprotein cholesterol (HDL-C; p?=?0.004), low-density lipoprotein cholesterol (LDL-C; p?=?0.001) as well as insulin resistance (p?<?0.001) between LADA group and type 2 DM patients. In conclusion, anti-GAD antibody and C-peptide level determination can be considered as confirmatory diagnostic markers for LADA, along with anti-IA2 assay, while other clinical and biochemical parameters can be useful for further characterizing LADA patients.     

成人迟发自身免疫性糖尿病与1、2型糖尿病临床表现的比较

目的：探讨成人迟发自身免疫性糖尿病（LADA）的临床特征，方法：评价谷氨酸脱羧酶抗体（GADA）、胰岛细胞抗体（ICA）阳性LADA患者各种急性和慢性并发症的患病率，并与速发型1和2型糖尿病（DM）相比较。结果：LADA患者的年龄，BMI，空腹及餐后C肽水平介于1和2型DM之间，LADA组29％患者有酮症，再次酮症的频率与1型相似，但至首次酮症的时间较长。视网膜病变患病率为19．5％，与1型DM相似；白内障患病率为48．8％，与2型DM相似；冠心病患病率与2型DM相似，高血压患病率介于1、2型DM之间。LADA组有微量白蛋白尿者较少，3组间显性肾病变。周围神经病变和高脂血症的患病率相似。结论：LADA的临床特征及急性和慢性并发症的患病率与1和2型DM有所不同。     

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。