自身免疫甲状腺病单个核细胞体外培养产生抗甲状腺球蛋白抗体

利用ELISA技术检测自身免疫甲状腺病(AITD)患者周围血单个核细胞(PBMC)体外培养产生甲状腺球蛋白抗体(TGA)。结果表明:体外培养AITD患者PBMC能够产生可测出的TGA,阳性率31.25％。桥本甲状腺炎(HT)较Graves甲亢(GD)更易体外产生TGA,阳性率分别为44.19％和16.22％。美洲商陆刺激体外产生TGA增加,而可溶性甲状腺球蛋白对体外产生TGA无刺激作用。抗甲状腺药物他巴唑能够抑制体外产生TGA。HT患者血清TGA水平与体外产生TGA呈正相关,但未观察到GD患者血清TGA与体外产生TGA的相关性。提示AITD患者体内存在可引起自身抗体产生的免疫调节紊乱、HT与GD在产生自身抗体的机制上可能有所不同。     

1型糖尿病伴自身免疫性甲状腺疾病的临床与遗传学特征

1型糖尿病(1 型DM)是一种T细胞介导的胰岛β细胞自身免疫破坏为主要发病机制的疾病.而自身免疫性甲状腺疾病(AIED)是一组以甲状腺内淋巴细胞浸润和甲状腺自身抗体产生为共同特征的异质性疾病,主要包括桥本病和Graves病.AITD是1型DM最常合并的自身免疫性疾病,而有关1型DM合并AITD的临床及免疫遗传学特征国内少见报道.     

自身免疫性甲状腺疾病与细胞凋亡

自身免疫性甲状腺疾病(autoimmune thyroid disease．AITD)是人类常见的自身免疫性疾病，主要包括Graves’病(GD)和桥本氏甲状腺炎(Hashimoto’s thyroiditis,HT)。AITD的病变部位主要发生在甲状腺，属于器官特异性自身免疫性疾病。多数学者研究认为，AITD发病是自身抗体的免疫应答或特异性T细胞介导的细胞免疫引起甲状腺组织的免疫损     

2型糖尿病合并牙周病患者龈沟液中TNF-α水平及临床意义

目的探讨2型糖尿病(T2DM)合并牙周病患者龈沟液(GCF)中肿瘤坏死因子(TNF)-α的水平及临床意义。方法选择2012年7月至2013年7月该院收治的52例T2DM合并牙周病患者作为观察组,另选同期该院52例单纯牙周病患者作为对照组。对比两组TNF-α、GCF及糖化血红蛋白(HbA1c)水平,分析糖尿病并发牙周病患者的HbA1c及GCF与TNF-α水平的相关性。结果观察组TNF-α、GCF水平均显著高于对照组(均P0.05);观察组Hb Alc≥8%者TNF-α及HbA1c水平均显著高于HbA1c8%者(均P0.05);HbA1c及GCF与TNF-α水平均呈正相关(r=0.768,0.821,均P0.05)。结论 T2DM并发牙周病者GCF内的TNF-α水平较高,且其与GCF和HbA1c呈相关性,对TNF-α水平监测有助于T2DM并发牙周病者的治疗。     

2型糖尿病患者合并低T_3综合征与糖化血红蛋白和胰岛β细胞功能相关性的研究

目的探讨住院T2DM患者合并低T3综合征发生率、临床特点和相关危险因素。方法249例T2DM患者根据甲状腺功能分为单纯T2DM(T2DM)组和T2DM合并低T3综合征(T2DM-LT3)组。检测HbA1c、FPG、FC-P、总三碘甲状腺原氨酸(TT3)、血清总甲状腺素(TT4)和促甲状腺激素(TSH)等指标。结果 T2DM-LT3组FC-P和胰岛β细胞功能指数(HOMA-β)低于T2DM组,糖尿病酮症发生率、HbA1c和FPG高于T2DM组(P0.05)。Pearson相关分析显示,TT3与HOMA-β和FC-P呈正相关(r=0.192、0.174,P0.01);与HbA1c、FPG和糖尿病酮症呈负相关(r=-0.319、-0.222、-0.202,P0.01)。Logistic回归分析显示,FC-P、TG和HbA1c是发生低T3综合征的危险因素。结论T2DM患者中低T3综合征可能与血糖控制不佳和胰岛功能受损相关。     

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。     

长链非编码RNA Blnc1在糖尿病肾脏疾病患者血清中的表达及临床意义

目的 探究长链非编码RNA(LncRNA)Blnc1在糖尿病肾脏疾病(DKD)患者血清中表达及其临床意义。方法 纳入我院56例DKD患者作为DKD组，50例单纯2型糖尿病(T2DM)患者作为T2DM组，56例同期体检健康者作为对照组。比较各组受试者一般临床资料、实验室检查结果及血清LncRNA Blnc1表达水平。采用Pearson相关分析探讨血清LncRNA Blnc1表达水平与临床指标的相关性。采用多因素logistic回归分析探讨T2DM患者发生DKD的危险因素。采用受试者工作特征(ROC)曲线分析血清LncRNA Blnc1对DKD的诊断价值。结果 T2DM组和DKD组患者血肌酐(SCr)、糖化血红蛋白(HbA1c)水平及血清LncRNA Blnc1表达水平均高于对照组(P<0.05)。DKD组患者SCr、HbA1c、尿白蛋白/肌酐比值(UACR)、24 h尿蛋白水平、糖尿病病程及血清LncRNA Blnc1表达水平均明显高于T2DM组，估算的肾小球滤过率(eGFR)低于T2DM组(P<0.05)。多因素logistic回归结果显示，糖尿病病程、UACR、HbA1c...     

血清25羟-维生素D、碘营养状况与自身免疫性甲状腺病的相关性

目的探讨25羟-维生素D[25(OH)D]水平、碘营养状况和自身免疫性甲状腺疾病(AITD)的相关性。方法通过检测380例粤中西部地区居民的空腹血清25(OH)D水平、甲状腺功能、甲状腺自身抗体、尿碘等相关指标等,并比较25(OH)D缺乏患者治疗后相关指标的差异,分析血清25(OH)D、碘营养状况对AITD发病的影响。结果 Graves病(GD)组、桥本甲状腺炎(HT)组25(OH)D3水平显著低于健康对照组(P<0.05)。GD组血清25(OH)D3水平与促甲状腺激素受体抗体(TRAb)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)呈显著负相关,与促甲状腺激素(TSH)呈显著正相关(P<0.01,P<0.05)。HT组血清25(OH)D3水平与抗甲状腺球蛋白抗体(TGAb)、抗甲状腺过氧化物酶抗体(TPOAb)、TSH呈显著负相关,与FT3、FT4呈显著正相关(P<0.01,P<0.05)。在GD组应用甲巯咪唑和HT组应用左甲状腺素的基础上加用活性维生素D连续治疗3个月后,GD组TRAb抗体水平明显降低,HT组TGAb、TPOAb抗体水平也明显降低(均P<0.05)。GD组和HT组尿碘中位数均较对照组高。尿碘高的AITD患者25(OH)D3水平缺乏更明显(P<0.05)。结论 AITD初发患者伴低维生素D水平,其中尿碘高的AITD患者25(OH)D3水平缺乏更明显。补充活性维生素D可降低其自身抗体水平。     

2型糖尿病患者游离三碘甲状腺原氨酸与血脂代谢关系的研究

目的评估不同血糖控制情况下T2DM患者甲状腺功能对血脂代谢的影响。方法选取住院T2DM患者595例,根据HbA1c水平分为HbA1c7.0%组108例、7.0%≤HbA1c9.0%组164例及HbA1c≥9.0%组323例,另选取健康体检者61名作为对照(NC)组。对各组指标进行比较,明确T2DM患者甲状腺功能指标与非高密度脂蛋白胆固醇(non-HDL-C)的关系。结果 HbA1c≥9.0%组non-HDL-C水平高于HbA1c7.0%组、7.0%≤HbA1c9.0%组和NC组[(3.84±1.16)vs(3.32±1.07),(3.59±0.96),(3.21±0.77)mmol/L,P均0.05]。HbA1c≥9.0%组游离三碘甲状腺原氨酸(FT3)水平低于HbA1c7.0%组、7.0%≤HbA1c9.0%组和NC组[(2.43±0.50)vs(2.69±0.46),(2.66±0.45),(2.91±0.44)pg/ml,P均0.05]。T2DM患者non-HDL-C与BMI、FPG和HbA1c呈正相关,与FT3呈负相关。多元线性回归分析提示,BMI、HbA1c和FT3是non-HDL-C的影响因素。结论随血糖升高,T2DM患者血脂代谢紊乱加重,FT3水平下降;FT3是影响T2DM患者血脂变化的重要因素。     

不同年龄2型糖尿病患者血糖达标状况及并发症

目的了解不同年龄2型糖尿病(T2DM)患者血糖达标情况,分析老年与青中年糖尿病患者并发症的发生情况。方法回顾性分析了2 264例T2DM患者,记录患者的一般资料、生化指标、糖化血红蛋白(HbA1c)及相关并发症检查结果。以HbA 1c7%为血糖达标标准进行血糖达标率分析。依据年龄分组,进行糖尿病并发症的分析。结果纳入的2 264例成人T2DM患者HbA1c达标率为42.4%。不同年龄组间(45岁、45～59岁、60～70岁、≥70岁)HbA1c达标率差异无统计学意义(P0.05)。老年组(≥60岁)和青中年组(60岁)的T2DM患者并发症:微血管并发症患病率分别为81.8%和66.6%;大血管并发症患病率分别为37.8%和14.9%,差异均有统计学意义(均P0.05)。老年组高血压、冠心病、脑血管病、骨质疏松的患病率明显高于青中年组,差异有统计学意义(P0.05);而老年组中合并血脂异常、超重及肥胖、糖尿病家族史者较青中年组少,差异有统计学意义(P0.05)。结论老年T2DM患者的慢性并发症发生率明显高于青中年患者。     

自身免疫性多内分泌腺病综合征Ⅲ型1例

患者女,28岁,以T1DM、DKA就诊,伴白癜风和毒性弥漫性甲状腺肿（Grave’s病）的临床特点,最终确诊“自身免疫性多内分泌腺病综合征（APS）Ⅲ型”。提示T1DM和自身免疫性甲状腺疾病（AITD）同时发生时,应注意APS存在。     

儿童初发糖尿病的诊断及分型指标研究

目的探讨儿童初发1型糖尿病（T1DM）与2型糖尿病（T2DM）的鉴别诊断指标。方法选择110例T1DM患儿（T1DM组）和20例T2DM患儿（T2DM组），采用SPSS10．0统计软件包分别比较其糖尿病家族史、发病年龄、发病至就诊时间、酮症酸中毒（DKA）、黑棘皮症发病率、体质量指数（BMI），腰围／身高比（W／H）、糖化血红蛋白（HbA1c）、空腹血糖（FBG）、餐后2h血糖（2hPG），空腹C肽（FCP）、空腹胰岛素（FINS）、胰岛素抵抗指数（IRI）、胰岛细胞抗体（ICA）、谷氨酸脱羧酶抗体（GAD）及有无胰岛素依赖。并设30例年龄、性别相匹配的健康儿童为对照组。结果①T1DM组发病年龄较小、发病急、DKA发病率高，多无糖尿病家族史，BMI及W／H低，无黑棘皮症，糖尿病自身免疫性抗体多阳性，FINS及FCP显著降低，无胰岛素抵抗，需胰岛素治疗才能使血糖达标及维持生命。②T2DM多有明显家族史、发病年龄多在10岁以后、发病缓慢，多伴有黑棘皮症，超重或肥胖，自身免疫性抗体多阴性，FINS及FCP较正常升高，显示胰岛素抵抗，DKA纠正后一般不需胰岛素治疗，通过减肥、运动、口服二甲双胍等可使血糖达标。结论①黑棘皮症、肥胖、胰岛素抵抗及无胰岛素依赖为诊断儿童初发T2DM的特异性指标。②FINS及FCP水平降低、无胰岛素抵抗、需依赖外源性胰岛素才能控制血糖和维持生命是诊断儿童TIDM的特异性指标。③发病年龄、家族史、DKA及自身免疫性抗体是重要的参考指标。     

Interferon therapy in hepatitis Cleading to chronic type 1 diabetes

AIM: To review the prevalence,clinical data and course of interferon-associated type 1 diabetes in chronic hepatitis C virus(HCV) infection.METHODS: Search of all interferon(INF)-related type 1diabetes mellitus(T1DM) cases published in the English literature from 1992 to December 2013 according to the key words: chronic hepatitis C infection,diabetes mellitus type 1,insulin dependent diabetes mellitus,and interferon treatment.We found 107 cases and analyzed their clinical and laboratory data and long-term followup.Due to the predominance of cases described in Japanese literature,we analyzed separately cases of Caucasian and Japanese origin.In addition we describe a representative case with HCV who developed INFrelated T1 DM.RESULTS: Our data show that INF treatment increases the risk of developing T1 DM by 10-18 fold compared with the corresponding general population and the median age of onset was 43 years(range: 24-66 years) in Caucasians and 52 years(range: 45-63 years) in Japanese.Most patients developed T1 DM during INF treatment,after a median time-period of 4.2 and 5.7 mo in Caucasian and Japanese groups,respectively.The clinical course was characterized by a fulminant course with abrupt severe hyperglycemia or ketoacidosis,a high titer of anti-islet autoantibodies and almost all patients(105/107) permanently required insulin therapy with a follow-up of up to 4 years.A substantial number of patients had evidence for other autoimmune disorders mainly thyroid diseases(25% and 31% in Caucasian and Japanese groups,respectively).CONCLUSION: INF-associated T1 DM in HCV has a fulminant course,often associated with other autoimmune diseases,and results almost inevitably in permanent insulin therapy requirement.     

Prevalence of diabetes-associated autoantibodies among patients presenting with type 2 diabetes and related metabolic differences

BackgroundTo explores the prevalence of autoantibodies (zinc transporter 8 autoantibodies (ZnT8A), antibodies to insulin (IAAs), glutamic acid decarboxylase autoantibody (GAD65)), the relation of the type of positive autoantibody and the number of positive autoantibodies with the glycemic and lipid profile of the patients with LADA (Latent Autoimmune Diabetes in Adults) and compares it to the metabolic profile of patients presenting with type 2 diabetes (T2DM).Methods263 patients with T2DM were recruited for this cross-sectional study in Tehran, Iran. Data from patients included complete medical history, GAD65, ZnT8A, IAA and routine metabolic laboratory workup. Assay for autoantibodies were conducted using ELISA kits. The association between autoantibodies and glycemic and lipid profile of patients with diabetes was assessed using univariate and multivariate regression analysis.ResultsOur study revealed that among 263 patients with T2DM, 29 (11%) cases were positive for IAAs, 9 (3.4%) for ZnT8A, and 12 (4.6%) for GAD65. Six (2.3%) of the patients had triple positive antibodies. Patients with positive results were younger, had lower body mass index (BMI), c-peptide, triglyceride, low-density lipoprotein (LDL), and higher high-density lipoprotein (HDL), HbA1c and fasting blood glucose (FBG) levels. Triple antibody positivity was significantly associated with lower levels of C-Peptide, Triglycerides, FBG, and HbA1c compared to triple negative antibodies.ConclusionPatients with LADA positive for either of the autoantibodies (GAD65, ZnT8 and IAA) presented with worse glycemic control. Measurement of these autoantibodies can assist in discrimination of these patients and help with earlier control of glycemic profile.     

Metabolic control in children and adolescents with insulin-dependent diabetes mellitus at King Abdul-Aziz University Hospital

Objective: Preventing long-term diabetic complications requires good metabolic control, especially in type 1 diabetes mellitus (T1DM). We describe the metabolic control of T1DM and the factors affecting it among children and adolescents attending the Pediatric Clinic at King Abdul-Aziz University Hospital. Methods: A retrospective cross-sectional study was conducted on T1DM children and adolescents who had attended the Pediatric Clinic at King Abdul-Aziz University Hospital from 2006 to 2010. Both clinical and laboratory data were reviewed for the enrolled cases. The mean age of the patients was 12.5±4.1 years. Ages ranged from 1 to 18 years (n=484: male=213, female= 271). 38.6% of the patients were pre-pubertal and 61.4% - pubertal. The patients were categorized into 3 age groups as 1-6 years (10.3%), 7-12 years (33.5%) and 13-18 years (56.2%). Results: The overall mean HbA1c was 9.4±2.4% and the duration of patient follow-up was 26±17 months. 10.3% of the patients were on conventional insulin regimens and 89.7% - on intensive insulin therapy. 31.4% had satisfactory HbA1c according to the American Diabetes Association guidelines. The duration of T1DM was 2.9±1.4 years. The patients with diabetes duration ≤2 years (45%) had a mean HbA1c of 8.7±1.8% and those with diabetes duration >2 years (55%) had a mean HbA1c value of 9.8±2.3% (p< 0.001). Conclusions: The metabolic control of T1DM children in our cohort was less satisfactory than in other studies. We recommend the promotion of physical exercise and family educational programs to improve the metabolic control of T1DM pediatric patients in our population.Conflict of interest:None declared.     

非糖尿病的2型糖尿病一级亲属血浆内皮素水平的研究

目的　研究 2型糖尿病 (T2 DM)及非糖尿病的 T2 DM的一级亲属 (FDRs)血浆内皮素 - 1 (ET- 1 )的变化 ,并探讨其与胰岛素抵抗(IR)、血脂、血糖、病程、吸烟以及糖尿病大血管并发症的关系。方法　测定 31例正常人 ,48例一级亲属 ,51例 T2 DM的血浆 ET- 1值。结果　胰岛素敏感指数 (IAI)在对照组、FDRs、T2 DM组逐渐降低 ,且有显著差异 (P<0 .0 5)。FDRs和 DM组血浆 ET- 1显著高于对照组 (P<0 .0 5)。血浆 ET- 1与IAI呈显著负相关 (r=- 0 .2 98,P<0 .0 1 )。在 T2 DM组血浆 ET- 1与病程呈正相关 (r=0 .353,P=0 .0 1 3) ,伴高血压、冠心病及周围血管病变的糖尿病患者与无并发症的糖尿病患者 ET- 1水平无显著差异。有糖尿病家族史者比无糖尿病家族史者血浆 ET- 1水平升高 (P<0 .0 5)。结论　 T2 DM及非糖尿病的 2型糖尿病一级亲属血浆 ET- 1升高。     

Association between body mass index and core components of metabolic syndrome in 1486 patients with type 1 diabetes mellitus in Japan (JDDM 13)

There is no recent study on the prevalence of overweight and obesity in patients with type 1 diabetes mellitus (T1DM) in Japan. Being overweight has a significant effect on the metabolic condition and glycemic control of such patients. In the present cross-sectional study, we investigated the effects of body mass index (BMI) on lipid profile, blood pressure, and glycemic control in patients with T1DM. In total, 1486 patients with T1DM (including 401 patients with early onset T1DM who were <20 years of age at diagnosis) were included. Patients were divided into four groups according to their BMI, and glycosylated hemoglobin (HbA1c), daily insulin dose per kg body weight, lipid profile, and blood pressure were compared between groups. We found that 15.7% of all patients were overweight (BMI >or= 25.0 kg/m(2)) and 2.0% were obese (BMI >or= 30.0 kg/m(2)), compared with 17.5% and 2.0%, respectively, in the early onset T1DM subgroup. Significant changes in lipid profiles and blood pressure were found with increasing BMI in both the entire population and the early onset T1DM subgroup. In the entire study population HbA1c and the body weight-adjusted daily insulin dose were significantly higher in patients with a BMI >or= 23 kg/m(2) compared with those with a BMI<23 kg/m(2); however, this was not the case in the early onset T1DM subgroup. This difference may be due to the relatively small number of patients in that subgroup. In conclusion, the prevalence of overweight and obesity in patients with T1DM was less than that in the normal Japanese population. For patients with T1DM, being overweight was associated with higher blood pressure and dyslipidemia. Furthermore, we cannot exclude an association between being overweight and the need for higher daily doses of insulin.     

A prospective study of thyroid function,morphology and autoimmunity in young patients with type 1 diabetes

OBJECTIVE: Thyroid autoantibodies (TA) and thyroid ultrasonography are widely used in the diagnosis of autoimmune thyroid disease (AITD). However, we know little of the significance of having ultrasonographic abnormalities (USabn) without having any other signs of AITD. In a previous population-based study of 105 young patients with type 1 diabetes (T1DM) we found a high prevalence (42%) of USabn. In the present study we evaluate the development of both USabn and TA in a 3-Year follow-up of this cohort. DESIGN: Of the 105 previously investigated children and adolescents with T1DM (aged 5-21 Years), 101 were re-examined. Serum concentrations of tri-iodothyronine (T(3)), thyroxine (T(4)), TSH, thyroid peroxidase antibodies (TPOab) and thyroglobulin antibodies (Tgab), as well as thyroid size and morphology were determined in all patients. RESULTS: During the 3 Years follow-up period, the prevalence of thyroid dysfunction increased from 5 to 8%, the prevalence of TPOab was unchanged at 13%, while the prevalence of Tgab decreased from 14 to 7%. The prevalence of USabn increased from 42 to 49%. Most patients presented USabn at both examinations. Patients with USabn had a higher prevalence of TA than those without USabn (P=0.038) and higher serum levels of TSH (P=0.027). All patients with thyroid dysfunction presented with USabn. However, many patients with USabn had no other signs of AITD. CONCLUSIONS: A high prevalence of thyroid dysfunction, TA and thyroid USabn were found in young patients with T1DM. Thyroid USabn was a sensitive but non-specific marker of AITD and is therefore unsuitable for screening purposes. Instead, we recommend regular screening using serum TSH in the follow-up of young diabetic patients.     

Heat-shock protein peptide DiaPep277 treatment in children with newly diagnosed type 1 diabetes: a randomised, double-blind phase II study

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a T-cell-mediated autoimmune disease that leads to the destruction of insulin-producing beta cells. Treatment with DiaPep277, a peptide derived from heat-shock protein 60 (hsp60), has been found to slow the deterioration of beta-cell function after clinical onset of diabetes in NOD mice and human adults. Our aim was to evaluate the efficacy and safety of DiaPep277 treatment in attenuating beta-cell destruction in children with recent-onset T1DM. METHODS: A prospective, randomized, double-blind, phase II design was used. The sample included 30 children (19 males) aged 7-14 years who had been diagnosed with T1DM from 53 to 116 days previously, and had basal C-peptide concentrations above 0.1 nmol/L. The children were randomized to receive subcutaneous injections of 1 mg DiaPep277 (15 patients) or 40 mg mannitol (placebo) at entry and at 1, 6, and 12 months. The duration of follow-up was 18 months. The groups were compared for stimulated C-peptide level, exogenous insulin dose, and HbA1c concentration. RESULTS: C-peptide levels similarly decreased over time in the DiaPep277- and placebo-treated patients. There was no significant difference in insulin dose or HbA1c concentration between the groups at any time point. No serious drug-related adverse effects were recorded throughout the study period. CONCLUSIONS: One-year treatment with DiaPep277 at a dosage of 1 mg is safe for use and well tolerated in children with recent-onset T1DM. However, it appears to have no beneficial effect in preserving beta-cell function or improving metabolic control.     

Interleukin-12p40 gene (IL-12B) polymorphism and Type 1 diabetes mellitus in Japanese: possible role in subjects without having high-risk HLA haplotypes

The present study was undertaken to clarify a role of interleukin-12p40 gene (IL-12B) polymorphism, located on chromosome 5q33-34 (IDDM 18), in Japanese subjects with Type 1 diabetes mellitus (T1DM) and autoimmune thyroid diseases (AITD). In 179 subjects with T1DM, 166 with AITD (128 with Graves' disease and 38 with Hashimoto's thyroiditis) and 115 healthy control subjects, the IL-12B 3'UTR A-C polymorphism was determined by PCR-RFLP method. In T1DM subjects, the genotype was also analyzed in relation to human leukocyte antigen (HLA)-DRB1-DQB1 haplotype status. There was a weak difference in the distribution of the genotype frequency between T1DM and control subjects, and the C allele frequency was higher in T1DM subjects (P<0.05). In 68 T1DM subjects without having high-risk HLA haplotypes to T1DM in this population, the genotype distribution and C allele frequency was significantly different from control subjects without high-risk HLA haplotypes (P<0.01), and from T1DM subjects with high-risk HLA haplotypes (n=111) (P<0.05). There was no difference in the genotype and allele frequencies between AITD and control subjects. In conclusion, the IL-12B 3'UTR A-C polymorphism did not seem to play a major role on genetic susceptibility to T1DM and AITD in Japanese, although the polymorphism conferred susceptibility in T1DM subjects without having high-risk HLA haplotypes. The IL-12B 3'UTR A-C polymorphism would be considered as a supplementary risk factor to T1DM in conjunction with HLA haplotypes.