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、     

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     

免疫介导的罕见类型糖尿病

根据１９９８年美国糖尿病学会（ＡＤＡ）关于糖尿病的诊断和分型的报告１型糖尿病是胰岛β细胞损毁导致胰岛素绝对缺乏。１型糖尿病又分为ⅠＡ免疫介导型和ⅠＢ特发型。其中Ｂ类为不明病因的１型糖尿病,虽有持续的胰岛素缺乏和酮症倾向但无自身免疫的证据;虽有很强的遗传特征但无ＨＬＡ相关性。Ａ类以前曾被称为胰岛素依赖型糖尿病、１型糖尿病、青年型糖尿病。自身免疫性胰岛破坏的标志物有岛细胞自身抗体（ＩＣＡｓ）,胰岛素自身抗体（ＩＡＡｓ）,谷氨酸脱羧酶抗体（ＧＡＤ６５）以及酪氨酸磷酸酶ＩＡ－２和ＩＡ－β抗体;大约８５％…     

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。     

ICA、64KDAb、IAA联合检测在1型糖尿病一级亲属中的预测价值

目的 为研究ＩＣＡ、６４ＫＤＡｂ、ＩＡＡ对１型糖尿病患者非糖尿病一级亲属的预测价值，对１型糖尿病患者及其非糖尿病一致亲属与普通人群中胰岛素自身抗体的分布情况进行了测定。方法 ①胰岛细胞抗体和各氨酸脱羧酶抗体采用ＥＬＩＳＡ法测定。②血清胰岛素自身抗体采用放射免疫分析法测定。结果 ＩＣＡ、６４ＫＤＡｂ、ＩＡＡ在１型糖尿病患者及其一级亲属中阳性率明显高于普通人群，６４ＫＤＡｂ阳性率高于ＩＣＡ、ＩＡＡ。结论 ６４ＫＤＡｂ较ＩＣＡ、ＩＡＡ具有更高的敏感性，预示１型糖尿病的标志。ＩＣＡ、６４ＫＤＡｂ１、ＩＡＡ三者联合检测可提高糖尿病的预测价值。     

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。     

糖尿病大鼠糖化终产物与主动脉壁细胞间粘附分子—1关系的 …

目的 了解糖尿病大鼠体内糖化终产物（ＡＧＥＳ）的产生与主动脉壁细胞间粘附分－１（ＩＣＡＭ－１）表达的并在体外确定ＡＧＥＳ是否具有独立致内皮细胞ＩＣＡＭ－１表达的作用。方法将糖尿病大鼠（ＤＭ组）、糖尿病氨基胍治疗大鼠（ＡＧ组）和正常大鼠（Ｃ组）分别喂是１、２、３、４个月后，其Ｈｂ－ＡＧＥｓ含量有主动脉壁ＩＣＡＭ－１表达情况。用流式细胞仪在半定量ＥＬＩＳＡ检测培养的内皮细胞ＡＧＥＳ作用后ＩＣＡＭ－１生     

磺脲类药物继发失效与成人晚发型自身免疫性糖尿病

目前已了解Ⅰ型糖尿病（ＤＭ）是一种针对胰岛β细胞的自身免疫性疾病,伴有胰小岛淋巴细胞浸润、循环中出现特异性的自身抗体,如胰岛细胞抗体（ＩＣＡ）、谷氨酸脱羧酶抗体（ＧＡＤＡｂ）等［１］。而Ⅱ型ＤＭ则是在胰岛素（Ｉｎｓ）抵抗伴Ｉｎｓ分泌相对或绝对不足基础上发生的［２］。但近年来研究发现,一些成年发病、起病时表现类似Ⅱ型ＤＭ的病人也有上述自身抗体,提示病人体内有慢性自身免疫性胰小岛炎。由此提出“成人晚发型自身免疫性糖尿病（ＬＡＤＡ）”的概念［３］。本研究通过测定磺脲类药物（ＳＵ）继发失效的成年ＤＭ患…     

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％     

谷氨酸脱羧酶自身抗体对胰岛素分泌的影响

目的　探讨１ 型糖尿病胰岛素缺乏机理及 Ｇ Ａ Ｄ Ａｂ 对胰岛细胞结构及功能的影响。方法　以改良的放射配体法筛选１ 型糖尿病患者 Ｇ Ａ Ｄ Ａｂ 阳性血清，以亲和层析法从该血清中分离纯化 Ｇ Ａ Ｄ Ａｂ ，以免疫荧光法观察 Ｇ Ａ Ｄ Ａｂ 与β细胞的结合；将纯化的 Ｇ Ａ Ｄ Ａｂ 及／ 或补体加入人胎胰岛细胞培养体系。结果　 Ｇ Ａ Ｄ Ａｂ 能够与β细胞结合，并使培养胰岛细胞的胰岛素释放量减少；透射电镜观察，加 Ｇ Ａ Ｄ Ａｂ 组β细胞胞浆颗粒减少；同时加入补体组β细胞的细胞膜被破坏。结论　１ 型糖尿病患者血清 Ｇ Ａ Ｄ Ａｂ 在体外能够抑制培养的人胎胰岛β细胞的胰岛素合成和释放，并且有补体依赖性细胞毒作用。     

Glutamic acid decarboxylase and ICA512/IA-2 autoantibodies as disease markers and relationship to residual beta-cell function and glycemic control in young type 1 diabetic patients

Circulating autoantibodies (Ab) to islet autoantigens, glutamic acid decarboxylase (GAD(65)), and tyrosine phosphatase ICA512/IA-2 have been proposed as predictive markers of type 1 diabetes mellitus. To ascertain residual beta-cell function and the clinical relevance for monitoring autoimmunity after clinical manifestation of disease, we studied 63 children at diagnosis of type 1 diabetes (mean SD age 7.5 +/- 4 years) and 91 adolescent patients with type 1 diabetes (age 14.7 +/- 1.6 years) with a mean duration of disease of 7 +/- 3.5) years. Forty-two normal adolescent subjects (age 14.6 +/- 1.8 years) without a family history of diabetes were the control group. Anti-GAD(65) and ICA512/IA-2 Ab were assessed by a quantitative radioimmunoprecipitation assay. The relationship between humoral autoimmunity and clinical parameters was explored. GAD(65) and ICA512/IA-2 Ab were detected in 56% and 63% of newly diagnosed children and the prevalence was not different in relationship to clinical characteristics. Levels of GAD(65) Ab positively correlated with diagnosis age (P <.05). Both Ab were associated with islet cell antibodies (ICA) (P <.05), but one fifth of patients had at least 1 of the 2 Ab and absent ICA. At onset, only age showed a significant relationship to residual C-peptide secretion. Among the cohort of patients with diabetes of short-mid duration, GAD(65) and ICA512/IA-2 Ab were present in 44% and 45% of cases (P >.05 and P <.05 v newly diagnosed children, respectively) and more patients were identified by these Ab (68%) than by ICA alone (34%) (P <.05). In this cohort, levels of ICA512/IA-2 Ab negatively correlated with levels of glycosylated hemoglobin (HbA(1c)) (P <.005) and with daily insulin requirement (P <.05). Moreover, the presence of some residual C-peptide secretion was significantly associated with the presence of ICA512/IA-2 Ab (P <.05). Our findings confirm that positivity for either GAD(65) or ICA512/IA-2 Ab is a highly sensitive marker of type 1 diabetes in the pediatric age group, identifying a group of patients with absent ICA immunofluorescence. The persistence of Ab to islet tyrosine phosphatase possibly represents a marker of better glycemic control and less insulin requirement, indicating residual beta-cell function, thus conferring clinical and prognostic relevance to these Ab, as well as potential usefulness in intervention strategies.     

NIDDM患者24小时血压监测的临床意义

用无创性动态血压监测（ＡＢＰＭ）对３０例血压正常的ＮＩＤＤＭ患者进行２４小时动态血压监测，并探讨其与自主神经病变和肾病的关系。结果：ＮＩＤＤＭ患者２４小时平均收缩压（１６．５±２．６ｋＰａ）、夜间收缩压（１６．３±３．１ｋＰａ）均较对照组（分别为１４．６±１．１ｋＰａ和１４．０±１．６ｋＰａ）明显增高；夜间收缩压负荷值增高（有１７例，占５７％）；夜间收缩压下降百分率降低（５．７％±５．０％对１０．４％±５．７％）；有神经病变的ＮＩＤＤＭ患者夜间收缩压下降百分率（３．６％±３．３％）及昼－夜尿白蛋白排泄差值（８．８％±８．５％）均低于无神经病变患者（分别为９．９％±５．１％和２０．６％±１１．１％）。提示糖尿病患者血压昼夜节律减弱或消失以及夜间血压增高可能参与糖尿病肾病的发生。     

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.     

Increased risk for endocrine autoimmunity in Italian type 2 diabetic patients with GAD65 autoantibodies

OBJECTIVE: Glutamic acid decarboxylase (GAD)65 autoantibodies (GAD65Ab) in type 2 diabetic subjects with secondary failure to sulphonylurea treatment identify the so-called latent autoimmune diabetes of the adult (LADA). The aim of our study was to estimate the risk for endocrine autoimmunity in type 2 diabetic subjects with GAD65Ab. DESIGN AND PATIENTS: We analysed serum samples from 600 adult subjects with a clinical diagnosis of type 2 diabetes mellitus for the presence and levels of GAD65Ab and antibodies directed against the islet autoantigen IA-2/ICA512 (IA-2/ICA512Ab). All the patients had been treated initially with hypoglycaemic agents and/or diet for at least 1 year. GAD65Ab+ subjects were studied for the presence of thyroid peroxidase autoantibodies (TPOAb), 21 hydroxylase autoantibodies (21OHAb) and frequency of HLA class II haplotypes. RESULTS: GAD65Ab were found in 67/600 (11%) and IA-2/ICA512Ab in 12/600 (2%) subjects (P < 0.0001). The presence of GAD65Ab, but not that of IA-2/ICA512Ab, was significantly associated with insulin therapy, low BMI (P < 0.0001) and low basal C-peptide (P < 0.01). Islet-cell antibodies (ICA) were detected in 43/67 (64%) GAD65Ab+ and in 10/12 (83%) IA-2/ICA512Ab + subjects. TPOAb occurred more frequently in GAD65Ab+ (16/67, 24%) than in GAD65Ab-subjects (9/174, 5%) (P < 0.0001). 21OHAb were detected only in GAD65Ab+ subjects (3/67, 4.5%) (P = 0.03 vs. GAD65Ab-subjects). None of the 21OHAb+ subjects had metabolic or clinical signs of adrenal dysfunction. HLA-DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) was significantly more frequent in GAD65Ab+ subjects than in healthy controls (OR = 5.42, corrected P < 0.0026). The presence of TPOAb was significantly associated with DR3-DQ2 (P = 0.024). CONCLUSIONS: Our study demonstrates that the presence of GAD65Ab identifies a subgroup of type 2 diabetic patients with high risk for thyroid and adrenal autoimmunity, and that both GAD65Ab and TPOAb are associated with the presence of HLA-DR3-DQ2, in these patients.     

Combined analysis of islet cell antibodies which cross-react with mouse pancreas,antibodies to the Mr 64,000 islet protein,and antibodies to glutamate decarboxylase in subjects at risk for IDDM

Summary With regard to progression to diabetes, ICA cross-reactive with mouse pancreas, antibodies to the M_r 64,000 islet antigen (64K), antibodies immunotrapping brain GAD activity, and IAA were analysed in 53 ICA-positive first-degree relatives of IDDM patients and 18 ICA-positive schoolchildren without a family history of diabetes. Sera from 29 (55 %) relatives did not bind to mouse pancreas, whereas 24 (45 %) displayed cross-species reaction. ICA titres on human and mouse pancreas were weakly correlated in the overall population (p <0.05) but more strongly (p <0.01) in only those subjects who displayed antibodies on tissues from both species. GAD and 64K antibodies were detected in 31 % and 35 % of relatives. In schoolchildren, the frequencies of cross-species reactive ICA (22 %), GAD antibodies (6 %), 64K antibodies (22 %), and IAA (6 %), were lower (p <0.05) than in relatives. A strong correlation (p <0.0001) was observed between GAD and 64K antibodies. GAD or 64K antibodies were strongly correlated with ICA on human pancreas (p <0.0001) but poorly with ICA on mouse pancreas (p =0.05). After pre-incubation of sera with brain homogenate, ICA titres were unaffected on mouse pancreas but reduced on human pancreas. ICA-positive subjects who displayed neither cross-species reactive ICA nor GAD or 64K antibodies were more frequent (p <0.05) among schoolchildren than relatives, whereas subjects who displayed all antibody specificities were more numerous (p <0.04) in relatives. All relatives with ICA binding only to human pancreas, as well as all schoolchildren, permanently displayed an AIRG higher than the first control percentile and remained non-diabetic. Five of ten relatives with cross-species reactive ICA, GAD and 64K antibodies at the same time displayed acute insulin response to glucose which fell below the first control percentile and developed the disease. The cross-species heterogeneity of ICA was thus confirmed in a large series of relatives and revealed in the general population. Detection of cross-species reactive ICA, GAD antibodies, or 64K antibodies enhances the prognostic significance after conventional ICA screening. The combination of these antibodies is more indicative of diabetes development than any antibody alone. Correlations between tests and absorption experiments indicate that GAD 64 is an ICA antigen on human but not on mouse pancreas, and that ICA which recognize GAD 64K coexist with others which react with mouse pancreas but not with GAD. A third ICA subset might have been revealed by high-titred ICA without either cross-species reactivity or GAD or 64K antibodies. This latter state was more frequent in the general population than in relatives and might typify an early immune response which may or may not progress. [Diabetologia (1994) 37: 491–499] Received: 29 July 1993 and in revised form: 25 November 1993     

空腹C-P、INS及胰岛细胞自身免疫抗体诊断儿童1型糖尿病的价值

为探讨儿童初发1型糖尿病（T1DM）的诊断指标，对33例T1DM患儿（观察组）分别测定其空腹血糖（FPG），糖化血红蛋白（HbA1c)，C－肽（C－P），胰岛素（INS），胰岛细胞抗体（ICA）及谷氨酸脱羧酶抗体（GAD），并与33例年龄，性别配对的健康儿童（对照组）作比较。结果显示，观察组除FPG，HbA1c显著升高外，C－P，INS，C－P／FPG，INS／FPG均显著低于对照组，以C－P／FPG最明显。提示空腹C－肽，INS，C－P／FPG，INS／FPG测定对诊断儿童初发T1DM有重要价值；胰岛细胞自免疫抗体测定对诊断T1DM有重要价值。     

Sexual dimorphism in transmission of expression of islet autoantibodies to offspring

Summary To help elucidate the mode of inheritance of insulin-dependent diabetes mellitus (IDDM), we measured GAD (glutamic acid decarboxylase) autoantibodies (GAD65Ab), insulin autoantibodies (IAA), and cytoplasmic islet cell autoantibodies (ICA) in 292 sequentially screened non-diabetic offspring of patients with IDDM. The prevalence of these islet autoantibodies was higher in offspring of diabetic fathers than in offspring of diabetic mothers. The prevalences of GAD65Ab, IAA, and ICA in the offspring of diabetic fathers were 11.5%, 10.8%, and 8.1% vs 2.1%, 1.4%, and 2.8%, respectively in the offspring of diabetic mothers (p<0.002, p<0.001, and p=0.06 NS). Amongst autoantibody-positive relatives the IAA and ICA levels were significantly higher in offspring of diabetic fathers than of diabetic mothers (p<0.002 and p<0.01, respectively). The frequencies of these autoantibodies were equal in male and female offspring. We conclude that IDDM mothers transmitted islet autoimmunity less frequently to their offspring than IDDM fathers. Given the markedly lower frequency of autoantibodies in offspring of mothers, larger sample sizes will be required to determine whether islet autoantibodies are influenced by age of IDDM onset of mothers, maternal age of pregnancy, and presence of diabetes in these mothers prior to conception.Abbreviations IDDM Insulin-dependent diabetes mellitus - GAD glutamic acid decarboxylase - GAD65Ab glutamic acid decarboxylase autoantibodies - IAA insulin autoantibodies - ICA cytoplasmic islet cell autoantibodies - JDF Juvenile Diabetes Foundation     

GAD65 antibody prevalence and association with thyroid antibodies, HLA-DR in Chinese children with type 1 diabetes mellitus

Persistent humoral autoimmunity to the enzyme glutamic acid decarboxylase (GAD) has been described in a substantial proportion of patients with type 1 diabetes mellitus. Higher prevalence of GAD antibody in diabetes patients using a new radioligand-binding assay with recombinant human GAD65 antibodies (GAD65Ab) has been seen in several studies. Using this method, we have reassessed the prevalence of GAD65Ab and investigated the association of GAD65Ab with HbA1C values, C-peptide values, HLA-DR typing and thyroid autoimmune antibody in 70 Chinese children with type 1 diabetes mellitus (mean age of onset 8.21+/-3.84 years, mean duration 3.39+/-2.54 years). Our result revealed that GAD65 antibodies were present in 54.3% (38/70) of diabetes children. There was no significant difference in gender, diabetes onset and duration, HbA1c, C-peptide concentration and frequencies of HLA DR3, DR4, DR9, DR3/DR4, DR3/DR9 and DR4/DR9 genotypes between GAD65Ab+ and GAD65Ab- groups. There was no negative correlation between GAD65Ab values and duration of diabetes in those with GAD65Ab positivity (r=-0.239, P>0.05). The frequencies of antimicrosomal and anti-thyroglobulin antibodies in GAD65Ab+ (13.5,8.1%, respectively) were not different from GAD65- patients (9.4,12.5%, respectively).     

Islet cell antibodies and glutamic acid decarboxylase antibodies, but not the clinical phenotype, help to identify type 1(1/2) diabetes in patients presenting with type 2 diabetes

This study was undertaken to determine which type 1 diabetes-associated autoantibodies and what clinical characteristics are most useful to identify patients with type 1(1/2) diabetes. We studied 125 patients, recently diagnosed clinically with type 2 diabetes for the presence of islet cell antibodies (ICA), insulin autoantibodies (IAA), antibodies to glutamic acid decarboxylase(GADAb), and IA-2a (IA-2Ab). Patients with a diagnosis of type 2 diabetes who met all of the following criteria at diagnosis were studied: age > or = 30 years, no history of ketonuria or ketoacidosis, and not requiring insulin treatment. Thirty-six patients (29%) were positive for at least 1 antibody. Thirty-two (26%) were ICA positive and 20 (16%) GADAb positive. Insulin autoantibodies and IA-2Ab occurred less frequently in 2 (1.6%) and 8 (6.4%) patients, respectively. There was no significant difference in the ages at diagnosis between the Ab(+) and Ab(-) patients, age in years (range) 47.2 (32 to 64) versus 51.2 (31 to 77), respectively, P =.06. Body mass index (BMI) was different in the 2 groups, with Ab(+) patients being less obese, BMI (range) 28.3 kg/m(2) (17.6 to 54.9) versus 32.0 kg/m(2) (19.2 to 68.8), respectively, P =.01. Clinical presentation of diabetes was more commonly symptomatic with polyuria and polydipsia in Ab(+) patients, while in Ab(-) patients, diagnosis was more often incidental, P =.002. However, more than 95% of patients overlapped in both age and BMI irrespective of antibody status. Similarly, 42% of Ab(+) patients had their diabetes diagnosed incidentally, while 29% of Ab(-) patients presented with polyuria and polydipsia. We therefore conclude that screening with antibodies, mainly ICA and GAD, but not age, BMI, or clinical presentation should be used to identify type 1(1/2) diabetes.     

Thyroid autoantibodies in Thai type 1 diabetic patients: clinical significance and their relationship with glutamic acid decarboxylase antibodies

OBJECTIVE: To study the clinical significance of thyroid autoantibodies in Thai patients with type 1 diabetes and their relationship with glutamic acid decarboxylase antibodies (GAD(65)Ab). METHODS: Thyroglobulin antibodies (TG-Ab) and thyroid peroxidase antibodies (TPO-Ab) were measured in 50 Thai type 1 diabetic patients. Forty-four patients also had GAD(65)Ab measured. Serum thyrotropin (TSH) was measured in all patients who had no history of thyroid disease regardless of thyroid antibody status. Clinical data including sex, age at onset and duration of diabetes, family history of diabetes, fasting c-peptide levels as well as frequencies of GAD(65)Ab were compared between patients with and without thyroid antibodies. GAD(65)Ab was also measured in 29 non-diabetic patients with hyperthyroid Graves' disease or Hashimoto thyroiditis as a control group. RESULTS: TG-Ab and TPO-Ab were positive in nine (18%) and 15 (30%) patients, respectively. Eight patients (16%) were positive for both antibodies. Two of 16 patients who were positive for TG-Ab or TPO-Ab had a previous history of hyperthyroidism prior to diabetes onset. Of the remainder, two were newly diagnosed with hyperthyroidism and one was found to have clinical hypothyroidism at the time of the study. None of 34 patients without thyroid antibodies had thyroid dysfunction. Eight patients with positive thyroid antibodies but without clinical thyroid dysfunction and 21 patients without thyroid antibodies were followed for up to 3 years, two patients of the first group developed hypothyroidism, whereas none of the latter developed thyroid dysfunction. The frequency of thyroid dysfunction at the time of initial study was significantly higher in patients with positive thyroid antibodies (3/14 vs. 0/34; P=0.021) and these patients who were initially euthyroid tended to have a higher risk of developing thyroid dysfunction (2/8 vs. 0/21; P=0.069). The frequency of thyroid antibodies was significantly increased in females and in those who had positive GAD(65)Ab. GAD(65)Ab was negative in all of the non-diabetic patients with autoimmune thyroid disease. CONCLUSIONS: About one-fourth of Thai patients with type 1 diabetes without thyroid disease had thyroid antibodies. The frequency of thyroid antibodies was increased in female and in GAD(65)Ab positive patients. The presence of thyroid antibodies is associated with a higher frequency of and may predict a higher risk for thyroid dysfunction in Thai type 1 diabetic patients.