暴发性1型糖尿病的流行特征、临床表型和病因探讨
|
摘要
暴发性1型糖尿病是近年来提出的1型糖尿病的新亚型。该病起病急骤,病情危重,预后凶险,严重危害人类健康,深入系统地研究暴发性1型糖尿病有非常重要的意义。然而,目前除日本外,其他国家对暴发性1型糖尿病的研究还非常之少。基于此,本研究分四部分就(1)暴发性1型糖尿病的流行病学特征；(2)暴发性1型糖尿病的临床表型；(3)暴发性1型糖尿病的病因探讨；(4)暴发性1型糖尿病相关的差异表达基因等问题进行了探讨,以期了解该型糖尿病在中国人群中的患病状况、分布特点和临床特征,通过对其病因和疾病相关基因的筛选探讨其可能的发病机制和临床病理过程。
第一部分暴发性1型糖尿病的流行病学特征调查
目的：
1.调查中南大学湘雅二医院暴发性1型糖尿病的患病状况；
2.调查暴发性1型糖尿病的主要时空人群分布特点和可能相关易感因素。
设计：
以医院为基础的横断面调查研究。
对象与方法：
回顾性分析2001-2008年中南大学湘雅二医院内分泌科住院糖尿病患者情况,从中筛选1型糖尿病患者,再从新发的1型糖尿病患者(排除LADA和酮症倾向糖尿病患者)中,按照Hanafusa等提出的诊断标准筛选暴发性1型糖尿病患者,由此分析暴发性1型糖尿病在住院糖尿病患者和新发1型糖尿病患者中的患病状况。另纳入全国暴发性1型糖尿病研究(F1 China)协作单位收集的符合诊断标准的13例患者,收集相关的临床资料,分析其时空人群分布特点及可能相关易感因素。
结果：
1.暴发性1型糖尿病占以医院为基础的连续住院糖尿病患者的1.24‰(11／8801),1型糖尿病患者的1.5%(11／729)和新发以酮症或酮症酸中毒起病的1型糖尿病患者的10.3%(11／107)。
2.暴发性1型糖尿病无明显地域差异,且无明显年份和月份的聚集。
3.暴发性1型糖尿病患者平均发病年龄为32±13岁。其患病率无明显性别差异,但女性患者起病时发生昏迷的比率明显高于男性患者(P=0.041),其糖化血红蛋白水平明显低于男性患者(P=0.018)。
4.3例(12.5%)暴发性1型糖尿病患者在药物过敏综合征后发病,3例(12.5%)暴发性1型糖尿病患者在妊娠期间发病。
结论：
1.暴发性1型糖尿病在湘雅二医院连续住院糖尿病患者中的患病率约为1‰,在新发1型糖尿病患者中的患病率约为10%。
2.暴发性1型糖尿病流行强度为散发。药物过敏综合征或妊娠可能为暴发性1型糖尿病的易感因素之一。
第二部分暴发性1型糖尿病的临床特征观察
目的：
1.观察暴发性1型糖尿病患者起病时的临床特征和伴随症状；
2.观察暴发性1型糖尿病患者3年随访中胰岛功能的变化。
设计：
病例对照研究。
对象与方法：
按照Hanafusa等提出的诊断标准,首先将本院诊断的新发1型糖尿病患者(107例)分为暴发性1型糖尿病组1(F1D1)(n=11)和非暴发性1型糖尿病组(nonF1D) (n=96),收集起病时的临床资料,分析其临床特点。另将外院收集的13例暴发性1型糖尿病患者并入前者(F1D1)成为暴发性1型糖尿病组2(F1D2)(n=24),同时从湖南1型糖尿病研究协作单位收集的新发1型糖尿病患者中筛选年龄性别匹配的经典和特发1型糖尿病患者分别组成经典1型糖尿病组(T1A)(n=48)和特发1型糖尿病组(T1B)(n=48),比较三组(F1D2,T1A和T1B)间起病时的临床特征。三组患者在起病后6,12,24,36月各随访1次,检测空腹和餐后2小时血糖、空腹和餐后2小时C肽和糖化血红蛋白,进行上述指标的比较。
结果：
1.与nonF1D组患者比较,F1D1组患者从出现高血糖症状到酮症酸中毒的时间更短、起病血糖更高、糖化血红蛋白,空腹和餐后C肽更低(P均<0.001)；F1D1组患者起病前出现流感样症状和腹部症状的频率明显高于nonF1D组患者(P<0.001)。F1D1组患者起病时GADA阳性率与nonF1D组比较无显著性差别,但滴度较低,有显著统计学差异(P<0.001)。
2.与T1A组和T1B组患者比较,F1D2组患者起病时的糖化血红蛋白、动脉血pH值,剩余碱和CO2CP更低,而血糖、血β-羟丁酸、血淀粉酶、谷丙转氨酶、谷草转氨酶,血尿素氮和血肌酐更高(P均<0.01)。F1D2组患者起病时血钾明显高于,血钠和血氯明显低于T1A和T1B组患者(P均<0.01)。
3.F1D2组患者起病后6,12,24,36个月时的空腹和餐后C肽较起病时无明显差异。F1D2组患者在起病后6月和12月时空腹和餐后C肽明显低于T1A组和T1B组患者(P均<0.01)。
结论：
1.暴发性1型糖尿病患者起病时较经典1型糖尿病和特发1型糖尿病患者存在更为严重的代谢失衡；
2.暴发性1型糖尿病患者在随访3年过程中未观察到胰岛功能的好转。
第三部分暴发性1型糖尿病的病因探讨
目的：
1.调查暴发性1型糖尿病患者HLA-DQ单体型情况；
2.调查暴发性1型糖尿病患者起病初期柯萨奇和腮腺炎病毒IgM情况；
3.调查暴发性1型糖尿病患者体液免疫和细胞免疫情况。
设计：
病例对照研究。
对象与方法：
1.暴发性1型糖尿病患者19例,提取全基因组DNA,采用PCR-直接测序法检测HLA-DQ单体型。然后将其与本中心以往经典1型糖尿病患者和正常人群HLA-DQ结果相比较。
2.暴发性1型糖尿病患者21例,经典1型糖尿病患者25例,正常对照组30例,收集起病3月内血清,采用酶联免疫吸附法(ELISA)检测柯萨奇和腮腺炎病毒IgM,比较其阳性率和滴度水平。
3.暴发性1型糖尿病患者20例,经典1型糖尿病患者40例,收集起病3月内血清,采用放射配体法检测胰岛自身抗体(GADA、IA-2A和ZnT8A),比较其阳性率和滴度水平,随访患者GADA滴度变化。比较胰岛自身抗体阳性与阴性患者的临床特征。
4.暴发性1型糖尿病患者6例,与其年龄性别匹配的经典1型糖尿病患者6例和正常对照7例,分离外周血单个核细胞(PBMCs),采用酶联免疫斑点法(ELISPOT)检测GAD-反应性T细胞。
结果：
1.暴发性1型糖尿病中频率最高的单体型为DQA1*03-DQB1*0303(18.4%),其次为DQA1*0102-DQB1*0601 (15.8%)。与经典1型糖尿病患者相比,暴发性1型糖尿病患者DQA1*03-DQB1*0303单体型的频率较低(P=0.02),而DQA1*0102-DQB1*0601、DQA1*05-DQB1*031、DQA1*0601-DQB1*0301和DQA1*03-DQB1*0402单体型的频率增高(P=0.004,P=0.03,P=0.014,P=0.000)。与正常对照相比,暴发性1型糖尿病患者DQA1*0102-DQB1*0601单体型的频率也增高(P=0.007)。
2.21例暴发性1型糖尿病患者中,1(5%)例患者柯萨奇病毒IgM阳性,5(24%)例患者腮腺炎病毒IgM阳性。暴发性1型糖尿病患者腮腺炎病毒IgM阳性率明显高于经典1型糖尿病和正常人群(P均<0.05)。
3.20例暴发性1型糖尿病患者中,7(35%)例患者GADA阳性,4(20%)例患者ZnT8A阳性,无1例患者IA-2A阳性,3(15%)例患者GADA和ZnT8A共同阳性,8(40%)例患者GADA或ZnT8A阳性。
暴发性1型糖尿病患者GADA和IA-2A阳性率和滴度明显低于经典1型糖尿病患者(P均<0.001)。胰岛自身抗体阳性和阴性的暴发性1型糖尿病患者之间的发病年龄、BMI、动脉血pH值、血清淀粉酶、CO2CP和胰岛素使用量均无统计学差异。
4.3(50%)例暴发性1型糖尿病患者和3(50%)例经典1型糖尿病患者PBMCs中检测出GAD-反应性T细胞,正常对照中未检测到GAD-反应性T细胞。
5.对7例患者GADA随访的结果显示：3例起病初期GADA阳性者,有2例分别于随访第2年或第3年后复查抗体转阴,另1例3年后复查抗体滴度增高(由0.34升至1.46)。
结论：
1. HLA DQA1*0102-DQB1*0601单体型可能为暴发性1型糖尿病的易感单体型；
2.部分暴发性1型糖尿病患者起病前有病毒感染；
3.自身免疫可能参与了部分暴发性1型糖尿病患者的发病。
第四部分暴发性1型糖尿病外周血单个核细胞基因表达谱初探
目的：
筛选暴发性1型糖尿病患者和正常对照外周血单个核细胞差异表达的基因。
设计：
病例对照研究。
对象和方法：
选择暴发性1型糖尿病6例,性别年龄匹配的正常对照6例。分离外周血单个核细胞,提取总mRNA,用琼脂糖电泳和分光光度计评价RNA的质量和完整性。随后对RNA进行线性扩增,逆转录并用Cy3标记,然后和Agilent人类全基因表达谱芯片(4×44k)杂交,洗片,最后用Agilent Scanner获取图像,标化数据后用GeneSpring软件分析结果。采用荧光实时定量PCR进行RNA表达水平的验证。
结果：
1.当P<0.05时,用T检验共筛选出两组间差异表达基因759个,其中上调的307个,下调的452个,当同时考虑P值(<0.05)和差异倍数(>1.1)时共筛选出差异表达的基因113个,上调的基因94个,下调的基因19个。
2.差异基因功能涉及细胞因子、趋化因子和受体分子、信号转导、转录因子、细胞凋亡和细胞骨架等。
3. TLR9, PHLDA1,CD1A和ELF4基因验证结果和表达谱芯片结果一致。
结论：
暴发性1型糖尿病患者的外周血单个核细胞和正常人群基因表达谱不同。其差异基因能为研究暴发性1型糖尿病的病理机制提供依据和进一步研究的线索。
Part 1 Epidemiological Features of Fulminant Type 1 Diabetes
Objective:
1.To investigate the prevalence of fulminant type 1 diabetes (F1D) in the Second Xiangya Hospital.
2.To investigate the temporal, spatial, population distribution and predisposing factors of F1D.
Design:Hospital-based cross-sectional investigation.
Subjects and Methods:
With the diagnostic criteria proposed by Hanafusa, fulminant type 1 diabetes were screened from the admitted diabetic patients in the Second Xiangya Hospital from 2001 to 2008. And the temporal, spatial and population distribution and the possible predisposing factors of F1D were analyzed in the patients mentioned above and that from F1 China Participating Hospitals.
Results:
1.Fulminant type 1 diabetes accounts for 1.24‰(11/8801) in the consecutive hospitalized diabetes,1.5%(11/729) in type 1 diabetes and 10.3%(11/107) in ketosis-or ketoacidosis-onset type 1 diabetes in the Second Xiangya hospital.
2.No regional difference or significant year and month preference of F1D were observed.
3.The average age of onset of fulminant type 1 diabetic patients were 32±13 year, and no sex difference was observed. Female patients were more prone to suffering coma (P=0.041) and having lower HbAlc levels (P=0.018) than the male patients.
4.Three (12.5%) fulminant type 1 diabetic patients were developing after drug hypersensitivity syndrome, and another three (12.5%) patients associated with pregnancy were observed.
Conclusion:
1.Fulminant type 1 diabetes accounts for about 0.1% of the hospitalized diabetes and 10% of the ketosis-or ketoacidosis-onset type 1 diabetes in the Second Xiangya hospital.
2.Pathogenesis of fulminant type 1 diabetes were possibly associated with pregnancy and DHS.
Part 2 Clinical Features of Fulminant Type 1 Diabetes
Objective:
To investigate the clinical features of fulminant type 1 diabetic patients at onset and the changes of the pancreatic beta-cell function during a three-year follow-up.
Design:Case-control study.
Subjects and Methods:
Firstly, using retrospective review of patient records, clinical features on admission were compared between fulminant (F1D1) (n=11) and non-fulminant (nonF1D) (n=96) type 1 diabetes in Second Xiangya Hospital. Secondly, Clinial features were compared among autoimmune type 1 diabetes (T1A), idiopathic type 1 diabetes (T1B) and F1D2 patients (11 from F1D1 and another 13 patients from the F1 China participating hospitals) after matching with age and sex. The following data were collected and compared among the three groups at 6,12,24,36 months after the onset, including fasting and 2-hour-postgrandial plasma glucose concentrations, and C-peptide levels, BMI and HbAlc levels.
Result:
1.Compared with patients of nonF1D, patients of F1D1 had remarkably shorter duration from the onset of hyperglycemic symptoms to ketosis-or ketoacidosis, and showed higher plasma glucose concentrations and lower HbAlc levels (P< 0.001, respectively) at onset. In addition, flu-like symptoms and abdominal symptoms were more frequently observed in F1D1 than that in nonF1D (P< 0.01, respectively). There was no significant difference of GADA positive rate between F1D1 and nonF1D patients, however the different GADA titers existed [0.0078 (-0.2590, 0.3430) vs.0.1176 (-0.0700,2.3400),P<0.01].
2.Compared with patients of T1A and T1B, patients of F1D2 had higher levels of plasma glucose, serum P-hydroxybutyric acid, serum amylase, glutamic-pyruvic transaminase, glutamic-pyruvic transaminas, urea nitrogen and serum creatinine, and lower levels of HbAlc, arterial pH, base excess and CO2CP at onset (all P<0.01). Patients of F1D2 had significantly lower serum sodium and chloride levels and higher serum potassium levels than the patients with T1A and TIB at onset (all P <0.01).
3. Both FCP and PCP levels of fulminant type 1 diabetes were not significantly different at 6,12,24 and 36 months after the onset of overt diabetes (all P>0.05). Both FCP and PCP levels of fulminant type 1 diabetes were significantly lower than the patients with T1A and T1B at 6 and 12 months after the onset (all P< 0.01).
Conclusion:
1.Metabolic derangement is more severe in fulminant type 1 diabetic patients than that in autoimmune and idiopathic type 1 diabetic patients at onset.
2.The pancreatic beta-cell function of fulminant type 1 diabetic patients were almost completely destroyed at onset and no recovery was observed during a three-year follow up.
Part 3 Etiological Investigation of Fulminant Type 1 Diabetes
Objective:
1. To investigate the HLA-DQ haplotypes of fulminant type 1 diabetes.
2. To investigate the IgM of Coxsackie and Mumps viruses of fulminant type 1 diabetes at onset.
3. To investigate the immunological features of fulminant type 1 diabetes.
Design:Case-control study.
Subjects and Methods:
1. Nineteen fulminant type 1 diabetic patients were recruited. Genomic DNA was extracted from whole blood using phenol C chloroform method and the alleles of HLA-DQ were tested by PCR and sequence-based genotyping (SBT). Frequencies of HLA-DQ haplotypes were compared to those of autoimmune type 1 diabetes and normal controls based on the data of our previous work.
2. Twenty-one fulminant type 1 diabetics,25 autoimmune type 1 diabetic patients and 30 normal controls were recruited. Serum were collected in the first 3 months after the onset. IgM of Coxsackie and Mumps viruses were tested with ELISA.
3. Twenty fulminant type 1 diabetics and forty age-and sex-matched autoimmune type 1 diabetics were recruited. Serum were collected in the first 3 months after the onset. And GADA(glutamic acid decarboxylase autoantibody), IA2A (protein tyrosine phosphatase antibody) and ZnT8A(zinc transporter 8 autoantibody) were tested with radioligand assay, and the GAD A were reexamed at 6,12,24,36 months after the onset. Clinical features were compared between autoantibody-positive and autoantibody-negative fulminant type 1 diabetic patients.
4. Six fulminant type 1 diabetic,6 autoimmune type 1 diabetic patients and 7 normal controls were recruited. PBMCs were isolated and the GAD-reactive T cells were detected by the enzyme-linked immunospot (ELISPOT) assay.
Results:
1. The most frequent haplotype found in F1D patients was DQA1*03-DQB1*0303 (18.4%), and the second was DQA1*0102-DQB1*0601 (15.8%). The frequency of DQA1*03-DQB 1*0303 haplotype was lower in F1D patients than that in autoimmune type 1 diabetes patients (P=0.02). However, the frequency of DQA1*0102-DQB1*0601 was higher in F1D patients than that in autoimmune type 1 diabetes patients and normal controls. (P=0.004, P =0.007, respectively)
2. One of 21 F1D patients were Coxsackie IgM positive, and 5 of 21 F1D patients were Mumps IgM positive.The positive rate of Mumps virus were higher in fulminant type 1 diabetic patients than that in autoimmune type 1 diabetic patients and normal controls(P<0.05, respectively).
3. Eight of 20 F1D patients were autoantibody-positive, including 7 patients GADA positive,4 patients ZnT8A positive and 3 patients both GADA and ZnT8A positive.
Both the positive rate and the titers of GADA and IA2A in F1D patients were lower than that in autoimmune type 1 diabetes(P<0.01, respectively). However, no significant differences in clinical features were observed in the study, including age at onset, BMI, arterial pH, serum amylase, CO2CP and insulin requirement.
4. Among subjects with fulminant type 1 diabetes (3/6), autoimmune type 1 diabetes (3/6) were recorded significant GAD-stimulated responses by ELISPOT assay, in contrast to none in normal controls.
5. Two patients with GADA positive at onset turned to negative after two or three years, while the index of another patient increased three years later (from 0.343 to 1.467).
Conclusion:
1. HLA DQA1*0102-DQB 1*0601 maybe a susceptible haplotype of F1D patients.
2. Parts of fulminant type 1 diabetic patients were infected with Coxsackie or Mumps virus before onset or at early stage.
3. Autoimmunity maybe involved in the pathogenesis of parts of fulminant type 1 diabetes.
Part 4 Genome-wide Expression Profiling of PBMCs in Fulminant Type 1 Diabetes
Objective:
To investigate differentially expressed genes of PBMCs between fulminant type 1 diabetic patients and normal controls.
Design:Case-control study.
Subjects and Methods:
Six fulminant type 1 dibetic patients and six age-and sex-matched normal controles were recruited. PBMCs were separated by Ficoll centrifugation and total mRNA were extracted with trizol reagent. Quality and integrity of total RNA were assessed by spectrophotometry and 1% agarose gel electrophoresis. RNA was reverse-transcribed and then labled with Cy3 in the course of in vitro transcription. Labled cDNAs were then purifed and hybridized to Agilent Whole Human Genome Microarray 4 X 44k. Slides were scaned with Agilent Scanner and data were normalized and analysed with GeneSpring. Comfirmation tests were determined by Real-Time PCR in four genes
Results:
1. Among 44,000 genes and ESTs,759 genes expressed differentially between PBMCs from fulminant type 1 diabetic patients and normal controls when P<0.05 (307 overexpressed and 452 underexpressed), and 113 genes expressed differentially when fold changes> 1.1 and P< 0.05 (94 overexpressed and 19 underexpressed).
2. These genes encode proteins with cytokines,chemokines and recepters, signal transduction, transcription factors, apoptosis and cytoskeleton.
3. The results of comfirmation tests were in accordance with the results of gene chip.
Conclusion:
Gene expression profiling of PBMCs can distiguish fulminant type 1 diabetic patients from healthy controls. The candidate genes provided important implications for etiology and pathogenesis of fulminant type 1 diabetes.
第一部分暴发性1型糖尿病的流行病学特征调查
目的：
1.调查中南大学湘雅二医院暴发性1型糖尿病的患病状况；
2.调查暴发性1型糖尿病的主要时空人群分布特点和可能相关易感因素。
设计：
以医院为基础的横断面调查研究。
对象与方法：
回顾性分析2001-2008年中南大学湘雅二医院内分泌科住院糖尿病患者情况,从中筛选1型糖尿病患者,再从新发的1型糖尿病患者(排除LADA和酮症倾向糖尿病患者)中,按照Hanafusa等提出的诊断标准筛选暴发性1型糖尿病患者,由此分析暴发性1型糖尿病在住院糖尿病患者和新发1型糖尿病患者中的患病状况。另纳入全国暴发性1型糖尿病研究(F1 China)协作单位收集的符合诊断标准的13例患者,收集相关的临床资料,分析其时空人群分布特点及可能相关易感因素。
结果：
1.暴发性1型糖尿病占以医院为基础的连续住院糖尿病患者的1.24‰(11／8801),1型糖尿病患者的1.5%(11／729)和新发以酮症或酮症酸中毒起病的1型糖尿病患者的10.3%(11／107)。
2.暴发性1型糖尿病无明显地域差异,且无明显年份和月份的聚集。
3.暴发性1型糖尿病患者平均发病年龄为32±13岁。其患病率无明显性别差异,但女性患者起病时发生昏迷的比率明显高于男性患者(P=0.041),其糖化血红蛋白水平明显低于男性患者(P=0.018)。
4.3例(12.5%)暴发性1型糖尿病患者在药物过敏综合征后发病,3例(12.5%)暴发性1型糖尿病患者在妊娠期间发病。
结论：
1.暴发性1型糖尿病在湘雅二医院连续住院糖尿病患者中的患病率约为1‰,在新发1型糖尿病患者中的患病率约为10%。
2.暴发性1型糖尿病流行强度为散发。药物过敏综合征或妊娠可能为暴发性1型糖尿病的易感因素之一。
第二部分暴发性1型糖尿病的临床特征观察
目的：
1.观察暴发性1型糖尿病患者起病时的临床特征和伴随症状；
2.观察暴发性1型糖尿病患者3年随访中胰岛功能的变化。
设计：
病例对照研究。
对象与方法：
按照Hanafusa等提出的诊断标准,首先将本院诊断的新发1型糖尿病患者(107例)分为暴发性1型糖尿病组1(F1D1)(n=11)和非暴发性1型糖尿病组(nonF1D) (n=96),收集起病时的临床资料,分析其临床特点。另将外院收集的13例暴发性1型糖尿病患者并入前者(F1D1)成为暴发性1型糖尿病组2(F1D2)(n=24),同时从湖南1型糖尿病研究协作单位收集的新发1型糖尿病患者中筛选年龄性别匹配的经典和特发1型糖尿病患者分别组成经典1型糖尿病组(T1A)(n=48)和特发1型糖尿病组(T1B)(n=48),比较三组(F1D2,T1A和T1B)间起病时的临床特征。三组患者在起病后6,12,24,36月各随访1次,检测空腹和餐后2小时血糖、空腹和餐后2小时C肽和糖化血红蛋白,进行上述指标的比较。
结果：
1.与nonF1D组患者比较,F1D1组患者从出现高血糖症状到酮症酸中毒的时间更短、起病血糖更高、糖化血红蛋白,空腹和餐后C肽更低(P均<0.001)；F1D1组患者起病前出现流感样症状和腹部症状的频率明显高于nonF1D组患者(P<0.001)。F1D1组患者起病时GADA阳性率与nonF1D组比较无显著性差别,但滴度较低,有显著统计学差异(P<0.001)。
2.与T1A组和T1B组患者比较,F1D2组患者起病时的糖化血红蛋白、动脉血pH值,剩余碱和CO2CP更低,而血糖、血β-羟丁酸、血淀粉酶、谷丙转氨酶、谷草转氨酶,血尿素氮和血肌酐更高(P均<0.01)。F1D2组患者起病时血钾明显高于,血钠和血氯明显低于T1A和T1B组患者(P均<0.01)。
3.F1D2组患者起病后6,12,24,36个月时的空腹和餐后C肽较起病时无明显差异。F1D2组患者在起病后6月和12月时空腹和餐后C肽明显低于T1A组和T1B组患者(P均<0.01)。
结论：
1.暴发性1型糖尿病患者起病时较经典1型糖尿病和特发1型糖尿病患者存在更为严重的代谢失衡；
2.暴发性1型糖尿病患者在随访3年过程中未观察到胰岛功能的好转。
第三部分暴发性1型糖尿病的病因探讨
目的：
1.调查暴发性1型糖尿病患者HLA-DQ单体型情况；
2.调查暴发性1型糖尿病患者起病初期柯萨奇和腮腺炎病毒IgM情况；
3.调查暴发性1型糖尿病患者体液免疫和细胞免疫情况。
设计：
病例对照研究。
对象与方法：
1.暴发性1型糖尿病患者19例,提取全基因组DNA,采用PCR-直接测序法检测HLA-DQ单体型。然后将其与本中心以往经典1型糖尿病患者和正常人群HLA-DQ结果相比较。
2.暴发性1型糖尿病患者21例,经典1型糖尿病患者25例,正常对照组30例,收集起病3月内血清,采用酶联免疫吸附法(ELISA)检测柯萨奇和腮腺炎病毒IgM,比较其阳性率和滴度水平。
3.暴发性1型糖尿病患者20例,经典1型糖尿病患者40例,收集起病3月内血清,采用放射配体法检测胰岛自身抗体(GADA、IA-2A和ZnT8A),比较其阳性率和滴度水平,随访患者GADA滴度变化。比较胰岛自身抗体阳性与阴性患者的临床特征。
4.暴发性1型糖尿病患者6例,与其年龄性别匹配的经典1型糖尿病患者6例和正常对照7例,分离外周血单个核细胞(PBMCs),采用酶联免疫斑点法(ELISPOT)检测GAD-反应性T细胞。
结果：
1.暴发性1型糖尿病中频率最高的单体型为DQA1*03-DQB1*0303(18.4%),其次为DQA1*0102-DQB1*0601 (15.8%)。与经典1型糖尿病患者相比,暴发性1型糖尿病患者DQA1*03-DQB1*0303单体型的频率较低(P=0.02),而DQA1*0102-DQB1*0601、DQA1*05-DQB1*031、DQA1*0601-DQB1*0301和DQA1*03-DQB1*0402单体型的频率增高(P=0.004,P=0.03,P=0.014,P=0.000)。与正常对照相比,暴发性1型糖尿病患者DQA1*0102-DQB1*0601单体型的频率也增高(P=0.007)。
2.21例暴发性1型糖尿病患者中,1(5%)例患者柯萨奇病毒IgM阳性,5(24%)例患者腮腺炎病毒IgM阳性。暴发性1型糖尿病患者腮腺炎病毒IgM阳性率明显高于经典1型糖尿病和正常人群(P均<0.05)。
3.20例暴发性1型糖尿病患者中,7(35%)例患者GADA阳性,4(20%)例患者ZnT8A阳性,无1例患者IA-2A阳性,3(15%)例患者GADA和ZnT8A共同阳性,8(40%)例患者GADA或ZnT8A阳性。
暴发性1型糖尿病患者GADA和IA-2A阳性率和滴度明显低于经典1型糖尿病患者(P均<0.001)。胰岛自身抗体阳性和阴性的暴发性1型糖尿病患者之间的发病年龄、BMI、动脉血pH值、血清淀粉酶、CO2CP和胰岛素使用量均无统计学差异。
4.3(50%)例暴发性1型糖尿病患者和3(50%)例经典1型糖尿病患者PBMCs中检测出GAD-反应性T细胞,正常对照中未检测到GAD-反应性T细胞。
5.对7例患者GADA随访的结果显示：3例起病初期GADA阳性者,有2例分别于随访第2年或第3年后复查抗体转阴,另1例3年后复查抗体滴度增高(由0.34升至1.46)。
结论：
1. HLA DQA1*0102-DQB1*0601单体型可能为暴发性1型糖尿病的易感单体型；
2.部分暴发性1型糖尿病患者起病前有病毒感染；
3.自身免疫可能参与了部分暴发性1型糖尿病患者的发病。
第四部分暴发性1型糖尿病外周血单个核细胞基因表达谱初探
目的：
筛选暴发性1型糖尿病患者和正常对照外周血单个核细胞差异表达的基因。
设计：
病例对照研究。
对象和方法：
选择暴发性1型糖尿病6例,性别年龄匹配的正常对照6例。分离外周血单个核细胞,提取总mRNA,用琼脂糖电泳和分光光度计评价RNA的质量和完整性。随后对RNA进行线性扩增,逆转录并用Cy3标记,然后和Agilent人类全基因表达谱芯片(4×44k)杂交,洗片,最后用Agilent Scanner获取图像,标化数据后用GeneSpring软件分析结果。采用荧光实时定量PCR进行RNA表达水平的验证。
结果：
1.当P<0.05时,用T检验共筛选出两组间差异表达基因759个,其中上调的307个,下调的452个,当同时考虑P值(<0.05)和差异倍数(>1.1)时共筛选出差异表达的基因113个,上调的基因94个,下调的基因19个。
2.差异基因功能涉及细胞因子、趋化因子和受体分子、信号转导、转录因子、细胞凋亡和细胞骨架等。
3. TLR9, PHLDA1,CD1A和ELF4基因验证结果和表达谱芯片结果一致。
结论：
暴发性1型糖尿病患者的外周血单个核细胞和正常人群基因表达谱不同。其差异基因能为研究暴发性1型糖尿病的病理机制提供依据和进一步研究的线索。
Part 1 Epidemiological Features of Fulminant Type 1 Diabetes
Objective:
1.To investigate the prevalence of fulminant type 1 diabetes (F1D) in the Second Xiangya Hospital.
2.To investigate the temporal, spatial, population distribution and predisposing factors of F1D.
Design:Hospital-based cross-sectional investigation.
Subjects and Methods:
With the diagnostic criteria proposed by Hanafusa, fulminant type 1 diabetes were screened from the admitted diabetic patients in the Second Xiangya Hospital from 2001 to 2008. And the temporal, spatial and population distribution and the possible predisposing factors of F1D were analyzed in the patients mentioned above and that from F1 China Participating Hospitals.
Results:
1.Fulminant type 1 diabetes accounts for 1.24‰(11/8801) in the consecutive hospitalized diabetes,1.5%(11/729) in type 1 diabetes and 10.3%(11/107) in ketosis-or ketoacidosis-onset type 1 diabetes in the Second Xiangya hospital.
2.No regional difference or significant year and month preference of F1D were observed.
3.The average age of onset of fulminant type 1 diabetic patients were 32±13 year, and no sex difference was observed. Female patients were more prone to suffering coma (P=0.041) and having lower HbAlc levels (P=0.018) than the male patients.
4.Three (12.5%) fulminant type 1 diabetic patients were developing after drug hypersensitivity syndrome, and another three (12.5%) patients associated with pregnancy were observed.
Conclusion:
1.Fulminant type 1 diabetes accounts for about 0.1% of the hospitalized diabetes and 10% of the ketosis-or ketoacidosis-onset type 1 diabetes in the Second Xiangya hospital.
2.Pathogenesis of fulminant type 1 diabetes were possibly associated with pregnancy and DHS.
Part 2 Clinical Features of Fulminant Type 1 Diabetes
Objective:
To investigate the clinical features of fulminant type 1 diabetic patients at onset and the changes of the pancreatic beta-cell function during a three-year follow-up.
Design:Case-control study.
Subjects and Methods:
Firstly, using retrospective review of patient records, clinical features on admission were compared between fulminant (F1D1) (n=11) and non-fulminant (nonF1D) (n=96) type 1 diabetes in Second Xiangya Hospital. Secondly, Clinial features were compared among autoimmune type 1 diabetes (T1A), idiopathic type 1 diabetes (T1B) and F1D2 patients (11 from F1D1 and another 13 patients from the F1 China participating hospitals) after matching with age and sex. The following data were collected and compared among the three groups at 6,12,24,36 months after the onset, including fasting and 2-hour-postgrandial plasma glucose concentrations, and C-peptide levels, BMI and HbAlc levels.
Result:
1.Compared with patients of nonF1D, patients of F1D1 had remarkably shorter duration from the onset of hyperglycemic symptoms to ketosis-or ketoacidosis, and showed higher plasma glucose concentrations and lower HbAlc levels (P< 0.001, respectively) at onset. In addition, flu-like symptoms and abdominal symptoms were more frequently observed in F1D1 than that in nonF1D (P< 0.01, respectively). There was no significant difference of GADA positive rate between F1D1 and nonF1D patients, however the different GADA titers existed [0.0078 (-0.2590, 0.3430) vs.0.1176 (-0.0700,2.3400),P<0.01].
2.Compared with patients of T1A and T1B, patients of F1D2 had higher levels of plasma glucose, serum P-hydroxybutyric acid, serum amylase, glutamic-pyruvic transaminase, glutamic-pyruvic transaminas, urea nitrogen and serum creatinine, and lower levels of HbAlc, arterial pH, base excess and CO2CP at onset (all P<0.01). Patients of F1D2 had significantly lower serum sodium and chloride levels and higher serum potassium levels than the patients with T1A and TIB at onset (all P <0.01).
3. Both FCP and PCP levels of fulminant type 1 diabetes were not significantly different at 6,12,24 and 36 months after the onset of overt diabetes (all P>0.05). Both FCP and PCP levels of fulminant type 1 diabetes were significantly lower than the patients with T1A and T1B at 6 and 12 months after the onset (all P< 0.01).
Conclusion:
1.Metabolic derangement is more severe in fulminant type 1 diabetic patients than that in autoimmune and idiopathic type 1 diabetic patients at onset.
2.The pancreatic beta-cell function of fulminant type 1 diabetic patients were almost completely destroyed at onset and no recovery was observed during a three-year follow up.
Part 3 Etiological Investigation of Fulminant Type 1 Diabetes
Objective:
1. To investigate the HLA-DQ haplotypes of fulminant type 1 diabetes.
2. To investigate the IgM of Coxsackie and Mumps viruses of fulminant type 1 diabetes at onset.
3. To investigate the immunological features of fulminant type 1 diabetes.
Design:Case-control study.
Subjects and Methods:
1. Nineteen fulminant type 1 diabetic patients were recruited. Genomic DNA was extracted from whole blood using phenol C chloroform method and the alleles of HLA-DQ were tested by PCR and sequence-based genotyping (SBT). Frequencies of HLA-DQ haplotypes were compared to those of autoimmune type 1 diabetes and normal controls based on the data of our previous work.
2. Twenty-one fulminant type 1 diabetics,25 autoimmune type 1 diabetic patients and 30 normal controls were recruited. Serum were collected in the first 3 months after the onset. IgM of Coxsackie and Mumps viruses were tested with ELISA.
3. Twenty fulminant type 1 diabetics and forty age-and sex-matched autoimmune type 1 diabetics were recruited. Serum were collected in the first 3 months after the onset. And GADA(glutamic acid decarboxylase autoantibody), IA2A (protein tyrosine phosphatase antibody) and ZnT8A(zinc transporter 8 autoantibody) were tested with radioligand assay, and the GAD A were reexamed at 6,12,24,36 months after the onset. Clinical features were compared between autoantibody-positive and autoantibody-negative fulminant type 1 diabetic patients.
4. Six fulminant type 1 diabetic,6 autoimmune type 1 diabetic patients and 7 normal controls were recruited. PBMCs were isolated and the GAD-reactive T cells were detected by the enzyme-linked immunospot (ELISPOT) assay.
Results:
1. The most frequent haplotype found in F1D patients was DQA1*03-DQB1*0303 (18.4%), and the second was DQA1*0102-DQB1*0601 (15.8%). The frequency of DQA1*03-DQB 1*0303 haplotype was lower in F1D patients than that in autoimmune type 1 diabetes patients (P=0.02). However, the frequency of DQA1*0102-DQB1*0601 was higher in F1D patients than that in autoimmune type 1 diabetes patients and normal controls. (P=0.004, P =0.007, respectively)
2. One of 21 F1D patients were Coxsackie IgM positive, and 5 of 21 F1D patients were Mumps IgM positive.The positive rate of Mumps virus were higher in fulminant type 1 diabetic patients than that in autoimmune type 1 diabetic patients and normal controls(P<0.05, respectively).
3. Eight of 20 F1D patients were autoantibody-positive, including 7 patients GADA positive,4 patients ZnT8A positive and 3 patients both GADA and ZnT8A positive.
Both the positive rate and the titers of GADA and IA2A in F1D patients were lower than that in autoimmune type 1 diabetes(P<0.01, respectively). However, no significant differences in clinical features were observed in the study, including age at onset, BMI, arterial pH, serum amylase, CO2CP and insulin requirement.
4. Among subjects with fulminant type 1 diabetes (3/6), autoimmune type 1 diabetes (3/6) were recorded significant GAD-stimulated responses by ELISPOT assay, in contrast to none in normal controls.
5. Two patients with GADA positive at onset turned to negative after two or three years, while the index of another patient increased three years later (from 0.343 to 1.467).
Conclusion:
1. HLA DQA1*0102-DQB 1*0601 maybe a susceptible haplotype of F1D patients.
2. Parts of fulminant type 1 diabetic patients were infected with Coxsackie or Mumps virus before onset or at early stage.
3. Autoimmunity maybe involved in the pathogenesis of parts of fulminant type 1 diabetes.
Part 4 Genome-wide Expression Profiling of PBMCs in Fulminant Type 1 Diabetes
Objective:
To investigate differentially expressed genes of PBMCs between fulminant type 1 diabetic patients and normal controls.
Design:Case-control study.
Subjects and Methods:
Six fulminant type 1 dibetic patients and six age-and sex-matched normal controles were recruited. PBMCs were separated by Ficoll centrifugation and total mRNA were extracted with trizol reagent. Quality and integrity of total RNA were assessed by spectrophotometry and 1% agarose gel electrophoresis. RNA was reverse-transcribed and then labled with Cy3 in the course of in vitro transcription. Labled cDNAs were then purifed and hybridized to Agilent Whole Human Genome Microarray 4 X 44k. Slides were scaned with Agilent Scanner and data were normalized and analysed with GeneSpring. Comfirmation tests were determined by Real-Time PCR in four genes
Results:
1. Among 44,000 genes and ESTs,759 genes expressed differentially between PBMCs from fulminant type 1 diabetic patients and normal controls when P<0.05 (307 overexpressed and 452 underexpressed), and 113 genes expressed differentially when fold changes> 1.1 and P< 0.05 (94 overexpressed and 19 underexpressed).
2. These genes encode proteins with cytokines,chemokines and recepters, signal transduction, transcription factors, apoptosis and cytoskeleton.
3. The results of comfirmation tests were in accordance with the results of gene chip.
Conclusion:
Gene expression profiling of PBMCs can distiguish fulminant type 1 diabetic patients from healthy controls. The candidate genes provided important implications for etiology and pathogenesis of fulminant type 1 diabetes.
引文
[1]. Leslie R D, Williams R, Pozzilli P. Clinical review:Type 1 diabetes and latent autoimmune diabetes in adults:one end of the rainbow. J Clin Endocrinol Metab 2006;91:1654-1659
[2]. Palmer J P, Hampe C S, Chiu H,et al. Is latent autoimmune diabetes in adults distinct from type 1 diabetes or just type 1 diabetes at an older age? Diabetes 2005;54 Suppl 2:S62-67
[3]. Umpierrez G E. Ketosis-prone type 2 diabetes:time to revise the classification of diabetes. Diabetes Care 2006;29:2755-2757
[4]. Balasubramanyam A, Nalini R, Hampe C S,et al. Syndromes of ketosis-prone diabetes mellitus. Endocr Rev 2008;29:292-302
[5]. Imagawa A, Hanafusa T, Miyagawa J,et al. A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies. Osaka IDDM Study Group. N Engl J Med 2000;342:301-307
[6]. Hanafusa T, Imagawa A. Fulminant type 1 diabetes:a novel clinical entity requiring special attention by all medical practitioners. Nat Clin Pract Endocrinol Metab 2007;3:36-45; quiz 32p following 69
[7]. Kilpatrick E S, Rigby A S, Atkin S L. Insulin resistance, the metabolic syndrome, and complication risk in type 1 diabetes:"double diabetes" in the Diabetes Control and Complications Trial. Diabetes Care 2007;30:707-712
[8]. Sherr J, Sosenko J, Skyler J S,et al. Prevention of type 1 diabetes:the time has come. Nat Clin Pract Endocrinol Metab 2008
[9]. Imagawa A, Hanafusa T, Miyagawa J,et al. A proposal of three distinct subtypes of type 1 diabetes mellitus based on clinical and pathological evidence. Ann Med 2000;32:539-543
[10]. Imagawa A, Hanafusa T, Uchigata Y,et al. Fulminant type 1 diabetes:a nationwide survey in Japan. Diabetes Care 2003;26:2345-2352
[11]. Cho Y M, Kim J T, Ko K S,et al. Fulminant type 1 diabetes in Korea:high prevalence among patients with adult-onset type 1 diabetes. Diabetologia 2007;50:2276-2279
[12]. 张弛,周智广,张冬梅,等.急骤起病伴胰酶升高的1型糖尿病患者临床和免疫学特征。中华医学杂志2005；85：967-971
[13]. 周健,贾伟平,包玉倩,等.暴发性1型糖尿病合并横纹肌溶解症一例.中华内科杂志2007；46(17)：944-945
[14]. Wang T, Xiao X H, Li W H,et al. Fulminant type 1 diabetes:Report of two cases. Chin Med J (Engl) 2008;121:181-182
[15]. Iyoda M, Kuroki A, Kato K,et al. A case of acute renal failure due to rhabdomyolysis, associated with non-autoimmune fulminant type 1B diabetes mellitus. Clin Nephrol 2003;59:301-304
[16]. Obi N, Katabami T, Asai S,et al. Fulminant type 1 diabetes complicated by leukemoid reaction. Intern Med 2008;47:847-851
[17]. Shimizu I, Makino H, Osawa H,et al. Association of fulminant type 1 diabetes with pregnancy. Diabetes Res Clin Pract 2003;62:33-38
[18]. Shimizu I, Makino H, Imagawa A,et al. Clinical and immunogenetic characteristics of fulminant type 1 diabetes associated with pregnancy. J Clin Endocrinol Metab 2006; 91:471-476
[19]. Imagawa A, Hanafusa T. Pathogenesis of fulminant type 1 diabetes. Rev Diabet Stud 2006;3:169-177
[20]. Tanaka S,Kobayashi T,Momotsu T. A novel subtype of type 1 diabetes mellitus. N Engl J Med 2000;342:2
[21]. Miura Y, Suzuki A, Sato I,et al. A case of fulminant type 1 diabetes with graves' disease. Diabetes Care 2002;25:1894-1895
[22]. Hamasaki A, Taniguchi T, Yamane S,et al. A case of fulminant type 1 diabetes associated with painless thyroiditis. Diabetes Care 2006;29:946-947
[23]. Sakaue S, Nagata M, Wakabayashi O,et al. A case of fulminant type 1 diabetes with elevated rheumatoid factor and the temporal presence of thyroid-stimulating hormone receptor antibody. Diabetes Care 2002;25:935-936
[24]. Endo T, Takizawa S, Tanaka S,et al. Amylase{alpha}-2A Autoantibodies: Novel Marker of Autoimmune Pancreatitis and Fulminant Type 1 Diabetes Mellitus. Diabetes 2008
[25]. Nagata M, Moriyama H, Kotani R,et al. Immunological aspects of fulminant type 1 diabetes. Diabetes Res Clin Pract 2007;77 Suppl 1:S99-103
[26]. Imagawa A, Hanafusa T, Uchigata Y,et al. Different contribution of class II HLA in fulminant and typical autoimmune type 1 diabetes mellitus. Diabetologia 2005;48:294-300
[27]. 王建平(导师：周智广).1型糖尿病胰岛自身抗体与HLA-DQ基因型的关系.[博士学位论文]长沙,中南大学,2006
[28]. Imagawa A, Hanafusa T. Fulminant type 1 diabetes mellitus. Endocr J 2006;53:577-584
[1]. Imagawa A, Hanafusa T, Miyagawa J, et al. A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies. Osaka IDDM Study Group. N Engl J Med 2000:342:301-307
[2]. Imagawa A, Hanafusa T, Uchigata Y, et al. Fulminant type 1 diabetes: a nationwide survey in Japan. Diabetes Care 2003:26:2345-2352
[3]. Cho Y M, Kim J T, Ko K S, et al. Fulminant type 1 diabetes in Korea: high prevalence among patients with adult-onset type 1 diabetes. Diabetologia 2007:50:2276-2279
[4]. Wang T, Xiao X H, Li W H,et al. Fulminant type 1 diabetes: report of two cases. Chin Med J (Engl) 2008:121:181-182
[5]． 周健，贾伟平，包玉倩，等．暴发性1型糖尿病合并横纹肌溶解症一例。中华内科杂志2007：46(17)：944-945
[6]． 陈欢欢，袁庆新，刘超．暴发性1型糖尿病1例．江苏医药2007：33(9)：969
[7]． 王彤，肖新华，李文慧，等．暴发性1型糖尿病二例并文献复习．中华内科杂志2008：47(4)：328—329
[8]. Chiou C C, Chung W H, Hung S I, et al. Fulminant type 1 diabetes mellitus caused by drug hypersensitivity syndrome with human herpesvirus 6 infection. J Am Acad Dermatol 2006;54:S14-17
[9]. Hanafusa T, Imagawa A. Fulminant type 1 diabetes: a novel clinical entity requiring special attention by all medical practitioners. Nat Clin Pract Endocrinol Metab 2007:3:36-45; quiz 32p following
[10]．黄干，周智广，颜湘，等．谷氨酸脱羧酶抗体和蛋白酪氨酸磷酸酶抗体检测的标准化研究．中华检验医学杂志2005：28(6)：59卜594值.中华内分泌代谢杂志2004:20(6):494-498
[12]. Gienke R. Vreugdenhil N C S, Anne Hoorens, et al. Acute Onset of Type 1 Diabetes Mellitus after Severe Echo virus 9 Infection:Putative Pathogenic Pathways. Clinical Infectious Diseases 2000;31:6
[13]. Jung T S, Chung S I, Kim M A, et al. A Korean patient with fulminant autoantibody-negative type 1 diabetes. Diabetes Care 2004:27:3023-3024
[14]. Taniyama M, Katsumata R, Aoki K, et al. A Filipino patient with fulminant type 1 diabetes. Diabetes Care 2004;27:842-843
[15]. Katsumata K. A Chinese patient presenting with clinical signs of fulminant type 1 diabetes mellitus. Intern Med 2005:44:967-969
[16]. Moreau C, Drui D, Arnault-Ouary G, et al. Fulminant type 1 diabetes in Caucasians: A report of three cases. Diabetes Metab 2008
[17]. 张弛,周智广,张冬梅,等.急骤起病伴胰酶增高的1型糖尿病患者的临床和免疫学特征.中华医学杂志2005;58:967-971
[18]. Yamamoto N, Fujita Y, Satoh S, et al. Fulminant type 1 diabetes during pregnancy: A case report and review of the literature. J Obstet Gynaecol Res 2007;33:552-556
[19]. Shimizu I, Makino H, Osawa H, et al. Association of fulminant type1 diabetes with pregnancy. Diabetes Res Clin Pract 2003:62:33-38
[20]. Shimizu I, Makino H, Imagawa A, et al. Clinical and immunogenetic characteristics of fulminant type 1 diabetes associated with pregnancy. J Clin Endocrinol Metab 2006:91:471-476
[21]. Seino Y, Yamauchi M, Hirai C, et al. A case of fulminant Type 1 diabetes associated with mexiletine hypersensitivity syndrome. Diabet Med 2004:21:1156-1157
[22]. Sekine N, Motokura T, Oki T, et al. Rapid loss of insulin secretion in a patient with fulminant type 1 diabetes mellitus and carbamazepine hypersensitivity syndrome. JAMA 2001:285:1153-1154
[23]. Sommers L. Allopurinol hypersensitivity syndrome associated with pancreatic exocrine abnormalities and new-onset diabetes raellitus. Arch Intern Med 2002;162:1190-1192
[24]. Hashimoto K, Yasukawa M, Tohyama M. Human herpesvirus 6 and drug allergy. Curr Opin Allergy Clin Immunol 2003;3:255-260
[1]. 周智广,郑超.暴发性1型糖尿病：一种不容忽视的糖尿病急危重症.内科急危重症杂志2008；14(4)：169-170
[2]. Hanafusa T, Imagawa A. Fulminant type 1 diabetes:a novel clinical entity requiring special attention by all medical practitioners. Nat Clin Pract Endocrinol Metab 2007;3:36-45; quiz 32p following 69
[3]. Katsumata K. A Chinese patient presenting with clinical signs of fulminant type 1 diabetes mellitus. Intern Med 2005;44:967-969
[4]. Jung J H, Hahm J R, Kim M A,et al. Fulminant autoantibody-negative and type 1A diabetes phenotypes in a Korean HLA identical dizygotic twin. Diabetes Care 2005;28:2330-2331
[5]. Imagawa A, Hanafusa T. Fulminant type 1 diabetes-is it an Asian-oriented disease? Intern Med 2005;44:913-914
[6]. Kawasaki E, Eguchi K. Is Type 1 diabetes in the Japanese population the same as among Caucasians? Ann N Y Acad Sci 2004; 1037:96-103
[7]. Jung T S, Chung S I, Kim M A,et al. A Korean patient with fulminant autoantibody-negative type 1 diabetes. Diabetes Care 2004;27:3023-3024
[8]. Iyoda M, Kuroki A, Kato K,et al. A case of acute renal failure due to rhabdomyolysis, associated with non-autoimmune fulminant type 1B diabetes mellitus. Clin Nephrol 2003;59:301-304
[9]. Bosi E, Minelli R, Bazzigaluppi E,et al. Fulminant autoimmune Type 1 diabetes during interferon-alpha therapy:a case of Thl-mediated disease? Diabet Med 2001; 18:329-332
[10]. Gienke R.Vreugdenhil N C S, Anne Hoorens, Ciska Rongen, Daniel G.Pipeleers,Willem J.G.Melchers, Bart O.Roep,andJochem M.D.Galama. Acute Onset of Type 1 Diabetes Mellitus after Severe Echo virus 9 Infection:Putative Pathogenic Pathways. Clinical Infectious Diseases 2000;31:6
[11]. Burgess J A, Kirkpatrick K L, Menser M A. Fulminant onset of diabetes mellitus during an attack of infectious mononucleosis. Med J Aust 1974;2:706-707
[12]. 王建平,周智广,黄干,等.IA-2A与GADA检测对1型糖尿病的诊断价值. 中华内分泌代谢杂志2004；20(6)：494-498
[13]. 李莉蓉,周智广,黄干,等.SOX13抗体对急性起病自身免疫糖尿病的诊断意义.中华内分泌代谢杂志2005；21(4)：357-360
[14]. 黄干,周智广,颜湘,等.谷氨酸脱羧酶抗体和蛋白酪氨酸磷酸酶抗体检测的标准化研究.中华检验医学杂志2005；28(6)：591-594
[15]. Imagawa A, Hanafusa T, Uchigata Y,et al. Fulminant type 1 diabetes:a nationwide survey in Japan. Diabetes Care 2003;26:2345-2352
[16]. Cho Y M, Kim J T, Ko K S,et al. Fulminant type 1 diabetes in Korea:high prevalence among patients with adult-onset type 1 diabetes. Diabetologia 2007;50:2276-2279
[17]. Moreau C, Drui D, Arnault-Ouary Qet al. Fulminant type 1 diabetes in Caucasians:A report of three cases. Diabetes Metab 2008
[18]. Tanaka S, Kobayashi T, Momotsu T. A novel subtype of type 1 diabetes mellitus. N Engl J Med 2000;342:2
[19]. Takahashi J, Nishijima K, Shukunami K,et al. Flare-up of serum amylase prior to onset of lethal ketoacidosis in a patient with fulminant type 1 diabetes. Diabetes Care 2006;29:461-462
[20]. Kahara T, Takamura T, Sakurai M,et al. Pancreatic exocrine and endocrine events occur concomitantly but independently during the course of fulminant type 1 diabetes. Diabetes Res Clin Pract 2006;71:241-246
[21]. Takaike H, Uchigata Y, Iwamoto Y,et al. Nationwide survey to compare the prevalence of transient elevation of liver transaminase during treatment of diabetic ketosis or ketoacidosis in new-onset acute and fulminant type 1 diabetes mellitus. Ann Med 2008;40:395-400
[22]. 周健,贾伟平,包玉倩,等.暴发性1型糖尿病合并横纹肌溶解症一例.中华内科杂志 2007；46(17)：944-945
[23]. Obi N, Katabami T, Asai S,et al. Fulminant type 1 diabetes complicated by leukemoid reaction. Intern Med 2008;47:847-851
[24]. Murase Y, Imagawa A, Hanafusa T,et al. Fulminant type 1 diabetes as a high risk group for diabetic microangiopathy--a nationwide 5-year-study in Japan. Diabetologia 2007;50:531-537
[1]. Imagawa A, Hanafusa T. Pathogenesis of fulminant type 1 diabetes. Rev Diabet Stud 2006;3:169-177
[2]. Kawasaki E, Matsuura N, Eguchi K. Type 1 diabetes in Japan. Diabetologia 2006;49:828-836
[3]. Imagawa A, Hanafusa T, Miyagawa J, et al. A proposal of three distinct subtypes of type 1 diabetes mellitus based on clinical and pathological evidence. Ann Med 2000;32:539-543
[4]. Umpierrez G E. Ketosis-prone type 2 diabetes:time to revise the classification of diabetes. Diabetes Care 2006;29:2755-2757
[5]. Imagawa A, Hanafusa T, Miyagawa J, et al. A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies. Osaka IDDM Study Group. N Engl J Med 2000;342:301-307
[6]. Hamasaki A, Taniguchi T, Yamane S, et al. A case of fulminant type 1 diabetes associated with painless thyroiditis. Diabetes Care 2006;29:946-947
[7]. Endo T, Takizawa S, Tanaka S, et al. Amylase{alpha}-2A Autoantibodies: Novel Marker of Autoimmune Pancreatitis and Fulminant Type 1 Diabetes Mellitus. Diabetes 2008
[8]. Tanaka S, Kobayashi T, Nakanishi K, et al. Association of HLA-DQ genotype in autoantibody-negative and rapid-onset type 1 diabetes. Diabetes Care 2002;25:2302-2307
[9]. 王建平,周智广,黄干,等.IA-2A与GADA检测对1型糖尿病的诊断价值.中华内分泌代谢杂志 2004；20(6)：494-498
[10]. 李莉蓉,周智广,黄干,等.SOX13抗体对急性起病自身免疫糖尿病的诊断意义.中华内分泌代谢杂志 2005；21(4)：357-360
[11]. 黄干,周智广,颜湘,等.谷氨酸脱羧酶抗体和蛋白酪氨酸磷酸酶抗体检测的标准化研究.中华检验医学杂志2005；28(6)：591-594
[12]. Wenzlau J M, Juhl K, Yu L, et al. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci U S A 2007;104:17040-17045
[13]. 张翼(导师：周智广).糖尿病谷氨酸脱羧酶(GAD65)反应性T细胞的检测及应用研究.[博士学位论文]长沙,中南大学,2005
[14]. 张翼,周智广,杨琳,等.部分特发性1型糖尿病存在谷氨酸脱羧酶65反应性T细胞.中华医学杂志2007；87(16)：1102-1105
[15]. 王建平(导师：周智广).1型糖尿病胰岛自身抗体与HLA-DQ基因型的关系.[博士学位论文]长沙,中南大学,2006
[16]. 王建平,张弛,林健,等.1型糖尿病患者胰岛自身抗体与人类白细胞抗原-DQ基因型的关系.中华医学杂志2007；87(34)：2380-2384
[17]. Kawasaki E, Eguchi K. Current aspects on the clinical immunology and genetics of autoimmune diabetes in Japan. Diabetes Res Clin Pract 2007;77 Suppl1:S104-109
[18]. Miura Y, Suzuki A, Sato I, et al. A case of fulminant type 1 diabetes with graves'disease. Diabetes Care 2002;25:1894-1895
[19]. Sakaue S, Nagata M, Wakabayashi O, et al. A case of fulminant type 1 diabetes with elevated rheumatoid factor and the temporal presence of thyroid-stimulating hormone receptor antibody. Diabetes Care 2002;25:935-936
[20]. Taniguchi T, Okazaki K, Okamoto M, et al. Autoantibodies against the exocrine pancreas in fulminant type 1 diabetes. Pancreas 2005;30:191-192
[21]. Nakagawa Y, Shimada A, Oikawa Y, et al. Two cases of "fulminant" type 1 diabetes suggesting involvement of autoimmunity. Ann N Y Acad Sci 2003;1005:359-361
[22]. Shimada A, Oikawa Y, Shigihara T, et al. A case of fulminant type 1 diabetes with strong evidence of autoimmunity. Diabetes Care 2002;25:1482-1483
[23]. Iwaoka T. A case of fulminant type 1 diabetes with transiently positive anti-GAD antibodies. Endocr J 2003;50:225-231
[24]. Sue M, Yoshihara A, Otani T, et al. Characteristics of fulminant type 1 diabetes mellitus. Med Sci Monit 2008;14:CS97-101
[25]. Bonifacio E, Scirpoli M, Kredel K, et al. Early autoantibody responses in prediabetes are IgG1 dominated and suggest antigen-specific regulation. J Immunol 1999; 163:525-532
[26]. Shimada A, Maruyama T. Encephalomyocarditis-virus-induced diabetes model resembles "fulminant" type 1 diabetes in humans. Diabetologia 2004;47:1854-1855
[27]. Sachdeva N, Asthana D. Cytokine quantitation:technologies and applications. Front Biosci 2007;12:4682-4695
[28]. 张翼,周智广.酶联免疫斑点法及其在自身免疫性糖尿病研究中的应用.国际内分泌代谢杂志2007；27(3)：166-168,189
[29]. Kotani R, Nagata M, Imagawa A, et al. T lymphocyte response against pancreatic beta cell antigens in fulminant Type 1 diabetes. Diabetologia 2004;47:1285-1291
[30]. Imagawa A, Hanafusa T, Uchigata Y, et al. Different contribution of class Ⅱ HLA in fulminant and typical autoimmune type 1 diabetes mellitus. Diabetologia 2005;48:294-300
[31]. Kawasaki E, Eguchi K. Genetics of fulminant type 1 diabetes. Ann N Y Acad Sci 2006; 1079:24-30
[32]. Jung J H, Hahm J R, Kim M A, et al. Fulminant autoantibody-negative and type 1A diabetes phenotypes in a Korean HLA identical dizygotic twin. Diabetes Care 2005;28:2330-2331
[33]. Wang J P, Zhou Z G, Lin J, et al. Islet autoantibodies are associated with HLA-DQ genotypes in Han Chinese patients with type 1 diabetes and their relatives. Tissue Antigens 2007;70:369-375
[34]. Lin J, Zhou Z G, Wang J P, et al. From Type 1, through LAD A, to type 2 diabetes:a continuous spectrum? Ann N Y Acad Sci 2008; 1150:99-102
[1]. Hanafusa T, Imagawa A. Fulminant type 1 diabetes:a novel clinical entity requiring special attention by all medical practitioners. Nat Clin Pract Endocrinol Metab 2007;3:36-45; quiz 32p following 69
[2]. Branca M. Genetics and medicine. Putting gene arrays to the test. Science 2003;300:238
[3]. Laudanski K, Miller-Graziano C, Xiao W, et al. Cell-specific expression and pathway analyses reveal alterations in trauma-related human T cell and monocyte pathways. Proc Natl Acad Sci USA 2006;103:15564-15569
[4]. Twine N C, Stover J A, Marshall B, et al. Disease-associated expression profiles in peripheral blood mononuclear cells from patients with advanced renal cell carcinoma. Cancer Res 2003;63:6069-6075
[5]. Greer B T, Khan J. Diagnostic classification of cancer using DNA microarrays and artificial intelligence. Ann N Y Acad Sci 2004; 1020:49-66
[6]. Snijders A M, Meijer G A, Brakenhoff R H, et al. Microarray techniques in pathology:tool or toy? Mol Pathol 2000;53:289-294
[7]. Burczynski M E, Twine N C, Dukart G, et al. Transcriptional profiles in peripheral blood mononuclear cells prognostic of clinical outcomes in patients with advanced renal cell carcinoma. Clin Cancer Res 2005;11:1181-1189
[8]. Wooster R. Cancer classification with DNA microarrays is less more? Trends Genet 2000; 16:327-329
[9]. Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. N Engl J Med 2009;360:790-800
[10]. Carrel L, Willard H F. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature 2005;434:400-404
[11]. Bomprezzi R, Ringner M, Kim S, et al. Gene expression profile in multiple sclerosis patients and healthy controls:identifying pathways relevant to disease. Hum Mol Genet 2003;12:2191-2199
[12]. Golub T R, Slonim D K, Tamayo P, et al. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 1999;286:531-537
[13]. Mehrian Shai R, Reichardt J K, Ya-Hsuan H, et al. Robustness of gene expression profiling in glioma specimen samplings and derived cell lines. Brain Res Mol Brain Res 2005;136:99-103
[14]. Rihn B H, Mohr S, McDowell S A, et al. Differential gene expression in mesothelioma. FEBS Lett 2000;480:95-100
[15]. van de Rijn M, Perou C M, Tibshirani R, et al. Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome. Am J Pathol 2002; 161:1991-1996
[16]. Parikh H, Carlsson E, Chutkow W A, et al. TXNIP regulates peripheral glucose metabolism in humans. PLoS Med 2007;4:e158
[17]. Maas K, Chan S, Parker J, et al. Cutting edge:molecular portrait of human autoimmune disease. J Immunol 2002;169:5-9
[18]. Cardozo A K, Kruhoffer M, Leeman R, et al. Identification of novel cytokine-induced genes in pancreatic beta-cells by high-density oligonucleotide arrays. Diabetes 2001;50:909-920
[19]. Eaves I A, Wicker L S, Ghandour G, et al. Combining mouse congenic strains and microarray gene expression analyses to study a complex trait:the NOD model of type 1 diabetes. Genome Res 2002;12:232-243
[20]. Gerling I C, Singh S, Lenchik N I, et al. New data analysis and mining approaches identify unique proteome and transcriptome markers of susceptibility to autoimmune diabetes. Mol Cell Proteomics 2006;5:293-305
[21]. Gunton J E, Kulkarni R N, Yim S, et al. Loss of ARNT/HIFlbeta mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetes. Cell 2005;122:337-349
[22]. Sreekumar R, Halvatsiotis P, Schimke J C, et al. Gene expression profile in skeletal muscle of type 2 diabetes and the effect of insulin treatment. Diabetes 2002;51:1913-1920
[23]. Shalev A, Pise-Masison C A, Radonovich M, et al. Oligonucleotide microarray analysis of intact human pancreatic islets:identification of glucose-responsive genes and a highly regulated TGFbeta signaling pathway. Endocrinology 2002;143:3695-3698
[24]. Pascual V, Allantaz F, Arce E, et al. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med 2005;201:1479-1486
[25]. Basu S, Larsson A, Vessby J, et al. Type 1 diabetes is associated with increased cyclooxygenase-and cytokine-mediated inflammation. Diabetes Care 2005;28:1371-1375
[26]. Maedler K, Sergeev P, Ris F, et al. Glucose-induced beta cell production of IL-1 beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest 2002;110:851-860
[27]. Laybutt D R, Weir G C, Kaneto H, et al. Overexpression of c-Myc in beta-cells of transgenic mice causes proliferation and apoptosis, downregulation of insulin gene expression, and diabetes. Diabetes 2002;51:1793-1804
[28]. Kawasaki E, Eguchi K. Genetics of fulminant type 1 diabetes. Ann N Y Acad Sci 2006; 1079:24-30
[29]. Imagawa A, Hanafusa T. Pathogenesis of fulminant type 1 diabetes. Rev Diabet Stud 2006;3:169-177
[30]. Steppan S, Kupfer K, Mayer A, et al. Genome wide expression profiling of human peripheral blood mononuclear cells stimulated with BAY 50-4798, a novel T cell selective interleukin-2 analog. J Immunother 2007;30:150-168
[31]. Ramilo O, Allman W, Chung W, et al. Gene expression patterns in blood leukocytes discriminate patients with acute infections. Blood 2007;109:2066-2077
[32]. Bouwens M, Afman L A, Muller M. Fasting induces changes in peripheral blood mononuclear cell gene expression profiles related to increases in fatty acid beta-oxidation:functional role of peroxisome proliferator activated receptor alpha in human peripheral blood mononuclear cells. Am J Clin Nutr 2007;86:1515-1523
[33]. Tang B M, McLean A S, Dawes I W, et al. Gene-expression profiling of peripheral blood mononuclear cells in sepsis. Crit Care Med 2009;37:882-888
[34]. Chuaqui R F, Bonner R F, Best C J, et al. Post-analysis follow-up and validation of microarray experiments. Nat Genet 2002;32 Suppl:509-514
[35]. Brazma A, Hingamp P, Quackenbush J, et al. Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat Genet 2001;29:365-371
[36]. 吴斌,沈自尹.基因表达谱芯片的数据分析.世界华人消化杂志2006;14：68-74
[37]. Brazma A, Vilo J. Gene expression data analysis. Microbes Infect 2001;3:823-829
[38]. Brazma A. On the importance of standardisation in life sciences. Bioinformatics 2001;17:113-114
[39]. Radu D L. Cellular mechanisms involved in experimental insulin-dependent diabetes mellitus. Roum Arch Microbiol Immunol 2001;60:203-226
[40]. Mathis D, Vence L, Benoist C. beta-Cell death during progression to diabetes. Nature 2001;414:792-798
[41]. Muller D, Huang G C, Amiel S, et al. Identification of insulin signaling elements in human beta-cells:autocrine regulation of insulin gene expression. Diabetes 2006;55:2835-2842
[1]. Imagawa A, Hanafusa T, Miyagawa J, et al. A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies. Osaka IDDM Study Group. N Engl J Med 2000;342:301-307
[2]. Tanaka S S, T.Kobayashi,T.Momotsu. A novel subtype of type 1 diabetes mellitus. N Engl J Med 2000;342:2
[3]. Hanafusa T, Imagawa A. Fulminant type 1 diabetes:a novel clinical entity requiring special attention by all medical practitioners. Nat Clin Pract Endocrinol Metab 2007;3:36-45; quiz 32p following 69
[4]. 周智广,郑超.暴发性1型糖尿病：一种不容忽视的糖尿病急危重症.内科急危重症杂志 2008；14(4)：169-170
[5]. Imagawa A, Hanafusa T, Miyagawa J, et al. A proposal of three distinct subtypes of type 1 diabetes mellitus based on clinical and pathological evidence. Ann Med 2000;32:539-543
[6]. Katsumata K. A Chinese patient presenting with clinical signs of fulminant type 1 diabetes mellitus. Intern Med 2005;44:967-969
[7]. Jung T S, Chung S I, Kim M A, et al. A Korean patient with fulminant autoantibody-negative type 1 diabetes. Diabetes Care 2004;27:3023-3024
[8]. Taniyama M, Katsumata R, Aoki K, et al. A Filipino patient with fulminant type 1 diabetes. Diabetes Care 2004;27:842-843
[9]. 张弛,周智广,张冬梅,等.急骤起病伴胰酶升高的1型糖尿病患者临床和免疫学特征.中华医学杂志 2005;85：967-971
[10]. 周建,贾伟平,包玉倩,等.暴发性1型糖尿病合并横纹肌溶解症一例.中华内科杂志 2007；46(17)：944-945
[11]. Wang T, Xiao X H, Li W H, et al. Fulminant type 1 diabetes:report of two cases. Chin Med J (Engl) 2008;121:181-182
[12]. 陈欢欢,袁庆新,刘超.暴发性1型糖尿病1例.江苏医药 2007;33(9):969
[13]. Kawasaki E, Eguchi K. Is Type 1 diabetes in the Japanese population the same as among Caucasians? Ann N Y Acad Sci 2004;1037:96-103
[14]. Imagawa A, Hanafusa T. Fulminant type 1 diabetes-is it an Asian-oriented disease? Intern Med 2005;44:913-914
[15]. Imagawa A, Hanafusa T, Uchigata Y, et al. Fulminant type 1 diabetes:a nationwide survey in Japan. Diabetes Care 2003;26:2345-2352
[16]. Cho Y M, Kim J T, Ko K S, et al. Fulminant type 1 diabetes in Korea:high prevalence among patients with adult-onset type 1 diabetes. Diabetologia 2007;50:2276-2279
[17]. Kawasaki E, Matsuura N, Eguchi K. Type 1 diabetes in Japan. Diabetologia 2006;49:828-836
[18]. Kawasaki E, Eguchi K. Current aspects on the clinical immunology and genetics of autoimmune diabetes in Japan. Diabetes Res Clin Pract 2007;77 Suppl1:S104-109
[19]. Yamamoto N, Fujita Y, Satoh S; et al. Fulminant type 1 diabetes during pregnancy:A case report and review of the literature. J Obstet Gynaecol Res 2007;33:552-556
[20]. Shimizu I, Makino H, Osawa H, et al. Association of fulminant type 1 diabetes with pregnancy. Diabetes Res Clin Pract 2003;62:33-38
[21]. Shimizu I, Makino H, Imagawa A, et al. Clinical and immunogenetic characteristics of fulminant type 1 diabetes associated with pregnancy. J Clin Endocrinol Metab 2006;91:471-476
[22]. Seino Y, Yamauchi M, Hirai C, et al. A case of fulminant Type 1 diabetes associated with mexiletine hypersensitivity syndrome. Diabet Med 2004;21:1156-1157
[23]. Sekine N, Motokura T, Oki T, et al. Rapid loss of insulin secretion in a patient with fulminant type 1 diabetes mellitus and carbamazepine hypersensitivity syndrome. JAMA 2001;285:1153-1154
[24]. Chiou C C, Chung W H, Hung S I, et al. Fulminant type 1 diabetes mellitus caused by drug hypersensitivity syndrome with human herpesvirus 6 infection. J Am Acad Dermatol 2006;54:S14-17
[25]. Sommers L. Allopurinol hypersensitivity syndrome associated with pancreatic exocrine abnormalities and new-onset diabetes mellitus.. Arch Intern Med 2002;162:1190-1192
[26]. Hashimoto K, Yasukawa M, Tohyama M. Human herpesvirus 6 and drug allergy. Curr Opin Allergy Clin Immunol 2003;3:255-260
[27]. Takahashi J, Nishijima K, Shukunami K, et al. Flare-up of serum amylase prior to onset of lethal ketoacidosis in a patient with fulminant type 1 diabetes. Diabetes Care 2006;29:461-462
[28]. Kahara T, Takamura T, Sakurai M, et al. Pancreatic exocrine and endocrine events occur concomitantly but independently during the course of fulminant type 1 diabetes. Diabetes Res Clin Pract 2006;71:241-246
[29]. Takaike H, Uchigata Y, Iwamoto Y, et al. Nationwide survey to compare the prevalence of transient elevation of liver transaminase during treatment of diabetic ketosis or ketoacidosis in new-onset acute and fulminant type 1 diabetes mellitus. Ann Med 2008;40:395-400
[30]. Obi N, Katabami T, Asai S, et al. Fulminant type 1 diabetes complicated by leukemoid reaction. Intern Med 2008;47:847-851
[31]. Imagawa A, Hanafusa T. Fulminant type 1 diabetes mellitus. Endocr J 2006;53:577-584
[32]. Sayama K, Imagawa A, Okita K, et al. Pancreatic beta and alpha cells are both decreased in patients with fulminant type 1 diabetes:a morphometrical assessment. Diabetologia 2005;48:1560-1564
[33]. Tanaka S, Endo T, Aida K, et al. Distinct diagnostic criteria of fulminant type 1 diabetes based on serum C-peptide response and HbAlc levels at onset. Diabetes Care 2004;27:1936-1941,
[34]. 杨晓琳,周智广.暴发性1型糖尿病.中国糖尿病杂志2006；14(4)：307-308
[35]. Shield J P, Wadsworth E J, Baum J D. The genetic contribution to disease pathogenesis in childhood diabetes is greatest in the very young. Diabet Med 1995;12:377-379
[36]. Gienke R.Vreugdenhil N C S, Anne Hoorens, Ciska Rongen, Daniel G.Pipeleers,Willem J.G.Melchers, Bart O.Roep,andJochem M.D.Galama. Acute Onset of Type 1 Diabetes Mellitus after Severe Echo virus 9 Infection:PutativePathogenicPathways. Clinical Infectious Diseases 2000;31:6
[37]. Sano H, Terasaki J, Tsutsumi C, et al. A case of fulminant type 1 diabetes mellitus after influenza B infection. Diabetes Res Clin Pract 2008;79:e8-9
[38]. Goto A, Takahashi Y, Kishimoto M, et al. A case of fulminant type 1 diabetes associated with significant elevation of mumps titers. Endocr J 2008;55:561-564
[39]. Imagawa A, Hanafusa T, Makino H, et al. High titres of IgA antibodies to enterovirus in fulminant type-1 diabetes. Diabetologia 2005;48:290-293
[40]. Ylipaasto P, Klingel K, Lindberg A M, et al. Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells. Diabetologia 2004;47:225-239
[41]. Burgess J A, Kirkpatrick K L, Menser M A. Fulminant onset of diabetes mellitus during an attack of infectious mononucleosis. Med J Aust 1974;2:706-707
[42].王建平(导师：周智广).1型糖尿病胰岛自身抗体与HLA-DQ基因型的关系.[博士学位论文]长沙,中南大学,2006
[43]. Mauvais-Jarvis F, Smith S B, Le May C, et al. PAX4 gene variations predispose to ketosis-prone diabetes. Hum Mol Genet 2004;13:3151-3159
[44]. Kawasaki E, Eguchi K. Genetics of fulminant type 1 diabetes. Ann N Y Acad Sci 2006; 1079:24-30
[45]. Katahira M, Ishiguro T, Segawa S, et al. Reevaluation of Human Leukocyte Antigen DR-DQ Haplotype and Genotype in Type 1 Diabetes in the Japanese Population. Horm Res 2008;69:284-289
[46]. Imagawa A, Hanafusa T, Iwahashi H, et al. Uniformity in clinical and HLA-DR status regardless of age and gender within fulminant type 1 diabetes. Diabetes Res Clin Pract 2008
[47]. Kawasaki E, Imagawa A, Makino H, et al. Differences in the contribution of the CTLA4 gene to susceptibility to fulminant and type 1A diabetes in Japanese patients. Diabetes Care 2008;31:1608-1610
[48]. Tanaka S, Kobayashi T, Nakanishi K, et al. Association of HLA-DQ genotype in autoantibody-negative and rapid-onset type 1 diabetes. Diabetes Care 2002;25:2302-2307
[49]. Imagawa A, Hanafusa T, Uchigata Y, et al. Different contribution of class II HLA in fulminant and typical autoimmune type 1 diabetes mellitus. Diabetologia 2005;48:294-300
[50]. Wang J P, Zhou Z G, Lin J, et al. Islet autoantibodies are associated with HLA-DQ genotypes in Han Chinese patients with type 1 diabetes and their relatives. Tissue Antigens 2007;70:369-375
[51]. Jung J H, Hahm J R, Kim M A, et al. Fulminant autoantibody-negative and type 1A diabetes phenotypes in a Korean HLA identical dizygotic twin. Diabetes Care 2005;28:2330-2331
[52]. Arai T, Hashimoto H, Kawai K, et al. Fulminant type 1 diabetes mellitus observed in insulin receptor substrate 2 deficient mice. Clin Exp Med 2008;8:93-99
[53]. Nagata M, Moriyama H, Kotani R, et al. Immunological aspects of 'fulminant type 1 diabetes'. Diabetes Res Clin Pract 2007;77 Suppl 1:S99-103
[54]. Sachdeva N, Asthana D. Cytokine quantitation:technologies and applications. Front Biosci 2007; 12:4682-4695
[55]. Miura Y, Suzuki A, Sato I, et al. A case of fulminant type 1 diabetes with graves' disease. Diabetes Care 2002;25:1894-1895
[56]. Hamasaki A, Taniguchi T, Yamane S, et al. A case of fulminant type 1 diabetes associated with painless thyroiditis. Diabetes Care 2006;29:946-947
[57]. Sakaue S, Nagata M, Wakabayashi O, et al. A case of fulminant type 1 diabetes with elevated rheumatoid factor and the temporal presence of thyroid-stimulating hormone receptor antibody. Diabetes Care 2002;25:935-936
[58]. Shimada A, Morimoto J, Kodama K, et al. T-cell-mediated autoimmunity may be involved in fulminant type 1 diabetes. Diabetes Care 2002;25:635-636
[59]. Shimada A, Oikawa Y, Shigihara T, et al. A case of fulminant type 1 diabetes with strong evidence of autoimmunity. Diabetes Care 2002;25:1482-1483
[60]. Nakagawa Y, Shimada A, Oikawa Y, et al. Two cases of "fulminant" type 1 diabetes suggesting involvement of autoimmunity. Ann N Y Acad Sci 2003; 1005:359-361
[61]. Bonifacio E, Scirpoli M, Kredel K, et al. Early autoantibody responses in prediabetes are IgG1 dominated and suggest antigen-specific regulation. J Immunol 1999;163:525-532
[62]. 张冬梅,周智广,黄干,等.以自发酮症起病的新发糖尿病患者的胰岛自身抗体检测.中华全科医师杂志2005；4(5)：273-276
[63]. 王建平,周智广,黄干,等.IA-2A与GADA检测对1型糖尿病的诊断价值.中华内分泌代谢杂志2004；20(6)：494-498
[64]. Wenzlau J M, Juhl K, Yu L, et al. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci USA 2007; 104:17040-17045
[65]. Sue M, Yoshihara A, Otani T, et al. Characteristics of fulminant type 1 diabetes mellitus. Med Sci Monit 2008;14:CS97-101
[66]. Rashba E J, Reich E P, Janeway C A, et al. Type 1 diabetes mellitus:an imbalance between effector and regulatory T cells? Acta Diabetol 1993;30:61-69
[67]. Radu D L. Cellular mechanisms involved in experimental insulin-dependent diabetes mellitus. Roum Arch Microbiol Immunol 2001;60:203-226
[68]. Alyanakian M A, You S, Damotte D, et al. Diversity of regulatory CD4+T cells controlling distinct organ-specific autoimmune diseases. Proc Natl Acad Sci U S A 2003;100:15806-15811
[69]. 何凌,周智广,罗建华,等.成人隐匿性自身免疫性糖尿病患者CD4+CD25+T细胞亚群的变化.中华糖尿病杂志2005；13(6)：428-431
[70]. 李莉蓉,周智广,黄干,等.SOX13抗体对急性起病自身免疫糖尿病的诊断意义.中华内分泌代谢杂志2005；21(4)：357-360
[71]. 张翼(导师：周智广).糖尿病谷氨酸脱羧酶(GAD65)反应性T细胞的检测及应用研究.[博士学位论文]长沙,中南大学,2005
[72]. 张翼,周智广,杨琳,等.部分特发性1型糖尿病存在谷氨酸脱羧酶65反应性T细胞.中华医学杂志2007；87(16)：1102-1105
[73]. Kotani R, Nagata M, Imagawa A, et al. T lymphocyte response against pancreatic beta cell antigens in fulminant Type 1 diabetes. Diabetologia 2004;47:1285-1291
[74]. Bosi E, Minelli R, Bazzigaluppi E, et al. Fulminant autoimmune Type 1 diabetes during interferon-alpha therapy:a case of Thl-mediated disease? Diabet Med 2001;18:329-332
[75]. Aoki K, Taniyama M, Nagayama C, et al. T cell immunity to glutamic acid decarboxylase in fulminant type 1 diabetes without significant elevation of serum amylase. Ann N Y Acad Sci 2006;1079:181-185
[76]. Murase Y, Imagawa A, Hanafusa T, et al. Fulminant type 1 diabetes as a high risk group for diabetic microangiopathy--a nationwide 5-year-study in Japan. Diabetologia 2007;50:531-537
[77]. Schade D S, Eaton R P. Pathogenesis of diabetic ketoacidosis:a reappraisal. Diabetes Care 1979;2:296-306
[78]. Murase-Mishiba Y, Imagawa A, Hanafusa T. Fulminant type 1 diabetes as a model of nature to explore the role of C-peptide. Exp Diabetes Res 2008;2008:819123
[79]. Hellerstrom C, Andersson A, Gunnarsson R. Regeneration of islet cells. Acta Endocrinol Suppl (Copenh) 1976;205:145-160
[2]. Palmer J P, Hampe C S, Chiu H,et al. Is latent autoimmune diabetes in adults distinct from type 1 diabetes or just type 1 diabetes at an older age? Diabetes 2005;54 Suppl 2:S62-67
[3]. Umpierrez G E. Ketosis-prone type 2 diabetes:time to revise the classification of diabetes. Diabetes Care 2006;29:2755-2757
[4]. Balasubramanyam A, Nalini R, Hampe C S,et al. Syndromes of ketosis-prone diabetes mellitus. Endocr Rev 2008;29:292-302
[5]. Imagawa A, Hanafusa T, Miyagawa J,et al. A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies. Osaka IDDM Study Group. N Engl J Med 2000;342:301-307
[6]. Hanafusa T, Imagawa A. Fulminant type 1 diabetes:a novel clinical entity requiring special attention by all medical practitioners. Nat Clin Pract Endocrinol Metab 2007;3:36-45; quiz 32p following 69
[7]. Kilpatrick E S, Rigby A S, Atkin S L. Insulin resistance, the metabolic syndrome, and complication risk in type 1 diabetes:"double diabetes" in the Diabetes Control and Complications Trial. Diabetes Care 2007;30:707-712
[8]. Sherr J, Sosenko J, Skyler J S,et al. Prevention of type 1 diabetes:the time has come. Nat Clin Pract Endocrinol Metab 2008
[9]. Imagawa A, Hanafusa T, Miyagawa J,et al. A proposal of three distinct subtypes of type 1 diabetes mellitus based on clinical and pathological evidence. Ann Med 2000;32:539-543
[10]. Imagawa A, Hanafusa T, Uchigata Y,et al. Fulminant type 1 diabetes:a nationwide survey in Japan. Diabetes Care 2003;26:2345-2352
[11]. Cho Y M, Kim J T, Ko K S,et al. Fulminant type 1 diabetes in Korea:high prevalence among patients with adult-onset type 1 diabetes. Diabetologia 2007;50:2276-2279
[12]. 张弛,周智广,张冬梅,等.急骤起病伴胰酶升高的1型糖尿病患者临床和免疫学特征。中华医学杂志2005；85：967-971
[13]. 周健,贾伟平,包玉倩,等.暴发性1型糖尿病合并横纹肌溶解症一例.中华内科杂志2007；46(17)：944-945
[14]. Wang T, Xiao X H, Li W H,et al. Fulminant type 1 diabetes:Report of two cases. Chin Med J (Engl) 2008;121:181-182
[15]. Iyoda M, Kuroki A, Kato K,et al. A case of acute renal failure due to rhabdomyolysis, associated with non-autoimmune fulminant type 1B diabetes mellitus. Clin Nephrol 2003;59:301-304
[16]. Obi N, Katabami T, Asai S,et al. Fulminant type 1 diabetes complicated by leukemoid reaction. Intern Med 2008;47:847-851
[17]. Shimizu I, Makino H, Osawa H,et al. Association of fulminant type 1 diabetes with pregnancy. Diabetes Res Clin Pract 2003;62:33-38
[18]. Shimizu I, Makino H, Imagawa A,et al. Clinical and immunogenetic characteristics of fulminant type 1 diabetes associated with pregnancy. J Clin Endocrinol Metab 2006; 91:471-476
[19]. Imagawa A, Hanafusa T. Pathogenesis of fulminant type 1 diabetes. Rev Diabet Stud 2006;3:169-177
[20]. Tanaka S,Kobayashi T,Momotsu T. A novel subtype of type 1 diabetes mellitus. N Engl J Med 2000;342:2
[21]. Miura Y, Suzuki A, Sato I,et al. A case of fulminant type 1 diabetes with graves' disease. Diabetes Care 2002;25:1894-1895
[22]. Hamasaki A, Taniguchi T, Yamane S,et al. A case of fulminant type 1 diabetes associated with painless thyroiditis. Diabetes Care 2006;29:946-947
[23]. Sakaue S, Nagata M, Wakabayashi O,et al. A case of fulminant type 1 diabetes with elevated rheumatoid factor and the temporal presence of thyroid-stimulating hormone receptor antibody. Diabetes Care 2002;25:935-936
[24]. Endo T, Takizawa S, Tanaka S,et al. Amylase{alpha}-2A Autoantibodies: Novel Marker of Autoimmune Pancreatitis and Fulminant Type 1 Diabetes Mellitus. Diabetes 2008
[25]. Nagata M, Moriyama H, Kotani R,et al. Immunological aspects of fulminant type 1 diabetes. Diabetes Res Clin Pract 2007;77 Suppl 1:S99-103
[26]. Imagawa A, Hanafusa T, Uchigata Y,et al. Different contribution of class II HLA in fulminant and typical autoimmune type 1 diabetes mellitus. Diabetologia 2005;48:294-300
[27]. 王建平(导师：周智广).1型糖尿病胰岛自身抗体与HLA-DQ基因型的关系.[博士学位论文]长沙,中南大学,2006
[28]. Imagawa A, Hanafusa T. Fulminant type 1 diabetes mellitus. Endocr J 2006;53:577-584
[1]. Imagawa A, Hanafusa T, Miyagawa J, et al. A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies. Osaka IDDM Study Group. N Engl J Med 2000:342:301-307
[2]. Imagawa A, Hanafusa T, Uchigata Y, et al. Fulminant type 1 diabetes: a nationwide survey in Japan. Diabetes Care 2003:26:2345-2352
[3]. Cho Y M, Kim J T, Ko K S, et al. Fulminant type 1 diabetes in Korea: high prevalence among patients with adult-onset type 1 diabetes. Diabetologia 2007:50:2276-2279
[4]. Wang T, Xiao X H, Li W H,et al. Fulminant type 1 diabetes: report of two cases. Chin Med J (Engl) 2008:121:181-182
[5]． 周健，贾伟平，包玉倩，等．暴发性1型糖尿病合并横纹肌溶解症一例。中华内科杂志2007：46(17)：944-945
[6]． 陈欢欢，袁庆新，刘超．暴发性1型糖尿病1例．江苏医药2007：33(9)：969
[7]． 王彤，肖新华，李文慧，等．暴发性1型糖尿病二例并文献复习．中华内科杂志2008：47(4)：328—329
[8]. Chiou C C, Chung W H, Hung S I, et al. Fulminant type 1 diabetes mellitus caused by drug hypersensitivity syndrome with human herpesvirus 6 infection. J Am Acad Dermatol 2006;54:S14-17
[9]. Hanafusa T, Imagawa A. Fulminant type 1 diabetes: a novel clinical entity requiring special attention by all medical practitioners. Nat Clin Pract Endocrinol Metab 2007:3:36-45; quiz 32p following
[10]．黄干，周智广，颜湘，等．谷氨酸脱羧酶抗体和蛋白酪氨酸磷酸酶抗体检测的标准化研究．中华检验医学杂志2005：28(6)：59卜594值.中华内分泌代谢杂志2004:20(6):494-498
[12]. Gienke R. Vreugdenhil N C S, Anne Hoorens, et al. Acute Onset of Type 1 Diabetes Mellitus after Severe Echo virus 9 Infection:Putative Pathogenic Pathways. Clinical Infectious Diseases 2000;31:6
[13]. Jung T S, Chung S I, Kim M A, et al. A Korean patient with fulminant autoantibody-negative type 1 diabetes. Diabetes Care 2004:27:3023-3024
[14]. Taniyama M, Katsumata R, Aoki K, et al. A Filipino patient with fulminant type 1 diabetes. Diabetes Care 2004;27:842-843
[15]. Katsumata K. A Chinese patient presenting with clinical signs of fulminant type 1 diabetes mellitus. Intern Med 2005:44:967-969
[16]. Moreau C, Drui D, Arnault-Ouary G, et al. Fulminant type 1 diabetes in Caucasians: A report of three cases. Diabetes Metab 2008
[17]. 张弛,周智广,张冬梅,等.急骤起病伴胰酶增高的1型糖尿病患者的临床和免疫学特征.中华医学杂志2005;58:967-971
[18]. Yamamoto N, Fujita Y, Satoh S, et al. Fulminant type 1 diabetes during pregnancy: A case report and review of the literature. J Obstet Gynaecol Res 2007;33:552-556
[19]. Shimizu I, Makino H, Osawa H, et al. Association of fulminant type1 diabetes with pregnancy. Diabetes Res Clin Pract 2003:62:33-38
[20]. Shimizu I, Makino H, Imagawa A, et al. Clinical and immunogenetic characteristics of fulminant type 1 diabetes associated with pregnancy. J Clin Endocrinol Metab 2006:91:471-476
[21]. Seino Y, Yamauchi M, Hirai C, et al. A case of fulminant Type 1 diabetes associated with mexiletine hypersensitivity syndrome. Diabet Med 2004:21:1156-1157
[22]. Sekine N, Motokura T, Oki T, et al. Rapid loss of insulin secretion in a patient with fulminant type 1 diabetes mellitus and carbamazepine hypersensitivity syndrome. JAMA 2001:285:1153-1154
[23]. Sommers L. Allopurinol hypersensitivity syndrome associated with pancreatic exocrine abnormalities and new-onset diabetes raellitus. Arch Intern Med 2002;162:1190-1192
[24]. Hashimoto K, Yasukawa M, Tohyama M. Human herpesvirus 6 and drug allergy. Curr Opin Allergy Clin Immunol 2003;3:255-260
[1]. 周智广,郑超.暴发性1型糖尿病：一种不容忽视的糖尿病急危重症.内科急危重症杂志2008；14(4)：169-170
[2]. Hanafusa T, Imagawa A. Fulminant type 1 diabetes:a novel clinical entity requiring special attention by all medical practitioners. Nat Clin Pract Endocrinol Metab 2007;3:36-45; quiz 32p following 69
[3]. Katsumata K. A Chinese patient presenting with clinical signs of fulminant type 1 diabetes mellitus. Intern Med 2005;44:967-969
[4]. Jung J H, Hahm J R, Kim M A,et al. Fulminant autoantibody-negative and type 1A diabetes phenotypes in a Korean HLA identical dizygotic twin. Diabetes Care 2005;28:2330-2331
[5]. Imagawa A, Hanafusa T. Fulminant type 1 diabetes-is it an Asian-oriented disease? Intern Med 2005;44:913-914
[6]. Kawasaki E, Eguchi K. Is Type 1 diabetes in the Japanese population the same as among Caucasians? Ann N Y Acad Sci 2004; 1037:96-103
[7]. Jung T S, Chung S I, Kim M A,et al. A Korean patient with fulminant autoantibody-negative type 1 diabetes. Diabetes Care 2004;27:3023-3024
[8]. Iyoda M, Kuroki A, Kato K,et al. A case of acute renal failure due to rhabdomyolysis, associated with non-autoimmune fulminant type 1B diabetes mellitus. Clin Nephrol 2003;59:301-304
[9]. Bosi E, Minelli R, Bazzigaluppi E,et al. Fulminant autoimmune Type 1 diabetes during interferon-alpha therapy:a case of Thl-mediated disease? Diabet Med 2001; 18:329-332
[10]. Gienke R.Vreugdenhil N C S, Anne Hoorens, Ciska Rongen, Daniel G.Pipeleers,Willem J.G.Melchers, Bart O.Roep,andJochem M.D.Galama. Acute Onset of Type 1 Diabetes Mellitus after Severe Echo virus 9 Infection:Putative Pathogenic Pathways. Clinical Infectious Diseases 2000;31:6
[11]. Burgess J A, Kirkpatrick K L, Menser M A. Fulminant onset of diabetes mellitus during an attack of infectious mononucleosis. Med J Aust 1974;2:706-707
[12]. 王建平,周智广,黄干,等.IA-2A与GADA检测对1型糖尿病的诊断价值. 中华内分泌代谢杂志2004；20(6)：494-498
[13]. 李莉蓉,周智广,黄干,等.SOX13抗体对急性起病自身免疫糖尿病的诊断意义.中华内分泌代谢杂志2005；21(4)：357-360
[14]. 黄干,周智广,颜湘,等.谷氨酸脱羧酶抗体和蛋白酪氨酸磷酸酶抗体检测的标准化研究.中华检验医学杂志2005；28(6)：591-594
[15]. Imagawa A, Hanafusa T, Uchigata Y,et al. Fulminant type 1 diabetes:a nationwide survey in Japan. Diabetes Care 2003;26:2345-2352
[16]. Cho Y M, Kim J T, Ko K S,et al. Fulminant type 1 diabetes in Korea:high prevalence among patients with adult-onset type 1 diabetes. Diabetologia 2007;50:2276-2279
[17]. Moreau C, Drui D, Arnault-Ouary Qet al. Fulminant type 1 diabetes in Caucasians:A report of three cases. Diabetes Metab 2008
[18]. Tanaka S, Kobayashi T, Momotsu T. A novel subtype of type 1 diabetes mellitus. N Engl J Med 2000;342:2
[19]. Takahashi J, Nishijima K, Shukunami K,et al. Flare-up of serum amylase prior to onset of lethal ketoacidosis in a patient with fulminant type 1 diabetes. Diabetes Care 2006;29:461-462
[20]. Kahara T, Takamura T, Sakurai M,et al. Pancreatic exocrine and endocrine events occur concomitantly but independently during the course of fulminant type 1 diabetes. Diabetes Res Clin Pract 2006;71:241-246
[21]. Takaike H, Uchigata Y, Iwamoto Y,et al. Nationwide survey to compare the prevalence of transient elevation of liver transaminase during treatment of diabetic ketosis or ketoacidosis in new-onset acute and fulminant type 1 diabetes mellitus. Ann Med 2008;40:395-400
[22]. 周健,贾伟平,包玉倩,等.暴发性1型糖尿病合并横纹肌溶解症一例.中华内科杂志 2007；46(17)：944-945
[23]. Obi N, Katabami T, Asai S,et al. Fulminant type 1 diabetes complicated by leukemoid reaction. Intern Med 2008;47:847-851
[24]. Murase Y, Imagawa A, Hanafusa T,et al. Fulminant type 1 diabetes as a high risk group for diabetic microangiopathy--a nationwide 5-year-study in Japan. Diabetologia 2007;50:531-537
[1]. Imagawa A, Hanafusa T. Pathogenesis of fulminant type 1 diabetes. Rev Diabet Stud 2006;3:169-177
[2]. Kawasaki E, Matsuura N, Eguchi K. Type 1 diabetes in Japan. Diabetologia 2006;49:828-836
[3]. Imagawa A, Hanafusa T, Miyagawa J, et al. A proposal of three distinct subtypes of type 1 diabetes mellitus based on clinical and pathological evidence. Ann Med 2000;32:539-543
[4]. Umpierrez G E. Ketosis-prone type 2 diabetes:time to revise the classification of diabetes. Diabetes Care 2006;29:2755-2757
[5]. Imagawa A, Hanafusa T, Miyagawa J, et al. A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies. Osaka IDDM Study Group. N Engl J Med 2000;342:301-307
[6]. Hamasaki A, Taniguchi T, Yamane S, et al. A case of fulminant type 1 diabetes associated with painless thyroiditis. Diabetes Care 2006;29:946-947
[7]. Endo T, Takizawa S, Tanaka S, et al. Amylase{alpha}-2A Autoantibodies: Novel Marker of Autoimmune Pancreatitis and Fulminant Type 1 Diabetes Mellitus. Diabetes 2008
[8]. Tanaka S, Kobayashi T, Nakanishi K, et al. Association of HLA-DQ genotype in autoantibody-negative and rapid-onset type 1 diabetes. Diabetes Care 2002;25:2302-2307
[9]. 王建平,周智广,黄干,等.IA-2A与GADA检测对1型糖尿病的诊断价值.中华内分泌代谢杂志 2004；20(6)：494-498
[10]. 李莉蓉,周智广,黄干,等.SOX13抗体对急性起病自身免疫糖尿病的诊断意义.中华内分泌代谢杂志 2005；21(4)：357-360
[11]. 黄干,周智广,颜湘,等.谷氨酸脱羧酶抗体和蛋白酪氨酸磷酸酶抗体检测的标准化研究.中华检验医学杂志2005；28(6)：591-594
[12]. Wenzlau J M, Juhl K, Yu L, et al. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci U S A 2007;104:17040-17045
[13]. 张翼(导师：周智广).糖尿病谷氨酸脱羧酶(GAD65)反应性T细胞的检测及应用研究.[博士学位论文]长沙,中南大学,2005
[14]. 张翼,周智广,杨琳,等.部分特发性1型糖尿病存在谷氨酸脱羧酶65反应性T细胞.中华医学杂志2007；87(16)：1102-1105
[15]. 王建平(导师：周智广).1型糖尿病胰岛自身抗体与HLA-DQ基因型的关系.[博士学位论文]长沙,中南大学,2006
[16]. 王建平,张弛,林健,等.1型糖尿病患者胰岛自身抗体与人类白细胞抗原-DQ基因型的关系.中华医学杂志2007；87(34)：2380-2384
[17]. Kawasaki E, Eguchi K. Current aspects on the clinical immunology and genetics of autoimmune diabetes in Japan. Diabetes Res Clin Pract 2007;77 Suppl1:S104-109
[18]. Miura Y, Suzuki A, Sato I, et al. A case of fulminant type 1 diabetes with graves'disease. Diabetes Care 2002;25:1894-1895
[19]. Sakaue S, Nagata M, Wakabayashi O, et al. A case of fulminant type 1 diabetes with elevated rheumatoid factor and the temporal presence of thyroid-stimulating hormone receptor antibody. Diabetes Care 2002;25:935-936
[20]. Taniguchi T, Okazaki K, Okamoto M, et al. Autoantibodies against the exocrine pancreas in fulminant type 1 diabetes. Pancreas 2005;30:191-192
[21]. Nakagawa Y, Shimada A, Oikawa Y, et al. Two cases of "fulminant" type 1 diabetes suggesting involvement of autoimmunity. Ann N Y Acad Sci 2003;1005:359-361
[22]. Shimada A, Oikawa Y, Shigihara T, et al. A case of fulminant type 1 diabetes with strong evidence of autoimmunity. Diabetes Care 2002;25:1482-1483
[23]. Iwaoka T. A case of fulminant type 1 diabetes with transiently positive anti-GAD antibodies. Endocr J 2003;50:225-231
[24]. Sue M, Yoshihara A, Otani T, et al. Characteristics of fulminant type 1 diabetes mellitus. Med Sci Monit 2008;14:CS97-101
[25]. Bonifacio E, Scirpoli M, Kredel K, et al. Early autoantibody responses in prediabetes are IgG1 dominated and suggest antigen-specific regulation. J Immunol 1999; 163:525-532
[26]. Shimada A, Maruyama T. Encephalomyocarditis-virus-induced diabetes model resembles "fulminant" type 1 diabetes in humans. Diabetologia 2004;47:1854-1855
[27]. Sachdeva N, Asthana D. Cytokine quantitation:technologies and applications. Front Biosci 2007;12:4682-4695
[28]. 张翼,周智广.酶联免疫斑点法及其在自身免疫性糖尿病研究中的应用.国际内分泌代谢杂志2007；27(3)：166-168,189
[29]. Kotani R, Nagata M, Imagawa A, et al. T lymphocyte response against pancreatic beta cell antigens in fulminant Type 1 diabetes. Diabetologia 2004;47:1285-1291
[30]. Imagawa A, Hanafusa T, Uchigata Y, et al. Different contribution of class Ⅱ HLA in fulminant and typical autoimmune type 1 diabetes mellitus. Diabetologia 2005;48:294-300
[31]. Kawasaki E, Eguchi K. Genetics of fulminant type 1 diabetes. Ann N Y Acad Sci 2006; 1079:24-30
[32]. Jung J H, Hahm J R, Kim M A, et al. Fulminant autoantibody-negative and type 1A diabetes phenotypes in a Korean HLA identical dizygotic twin. Diabetes Care 2005;28:2330-2331
[33]. Wang J P, Zhou Z G, Lin J, et al. Islet autoantibodies are associated with HLA-DQ genotypes in Han Chinese patients with type 1 diabetes and their relatives. Tissue Antigens 2007;70:369-375
[34]. Lin J, Zhou Z G, Wang J P, et al. From Type 1, through LAD A, to type 2 diabetes:a continuous spectrum? Ann N Y Acad Sci 2008; 1150:99-102
[1]. Hanafusa T, Imagawa A. Fulminant type 1 diabetes:a novel clinical entity requiring special attention by all medical practitioners. Nat Clin Pract Endocrinol Metab 2007;3:36-45; quiz 32p following 69
[2]. Branca M. Genetics and medicine. Putting gene arrays to the test. Science 2003;300:238
[3]. Laudanski K, Miller-Graziano C, Xiao W, et al. Cell-specific expression and pathway analyses reveal alterations in trauma-related human T cell and monocyte pathways. Proc Natl Acad Sci USA 2006;103:15564-15569
[4]. Twine N C, Stover J A, Marshall B, et al. Disease-associated expression profiles in peripheral blood mononuclear cells from patients with advanced renal cell carcinoma. Cancer Res 2003;63:6069-6075
[5]. Greer B T, Khan J. Diagnostic classification of cancer using DNA microarrays and artificial intelligence. Ann N Y Acad Sci 2004; 1020:49-66
[6]. Snijders A M, Meijer G A, Brakenhoff R H, et al. Microarray techniques in pathology:tool or toy? Mol Pathol 2000;53:289-294
[7]. Burczynski M E, Twine N C, Dukart G, et al. Transcriptional profiles in peripheral blood mononuclear cells prognostic of clinical outcomes in patients with advanced renal cell carcinoma. Clin Cancer Res 2005;11:1181-1189
[8]. Wooster R. Cancer classification with DNA microarrays is less more? Trends Genet 2000; 16:327-329
[9]. Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. N Engl J Med 2009;360:790-800
[10]. Carrel L, Willard H F. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature 2005;434:400-404
[11]. Bomprezzi R, Ringner M, Kim S, et al. Gene expression profile in multiple sclerosis patients and healthy controls:identifying pathways relevant to disease. Hum Mol Genet 2003;12:2191-2199
[12]. Golub T R, Slonim D K, Tamayo P, et al. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 1999;286:531-537
[13]. Mehrian Shai R, Reichardt J K, Ya-Hsuan H, et al. Robustness of gene expression profiling in glioma specimen samplings and derived cell lines. Brain Res Mol Brain Res 2005;136:99-103
[14]. Rihn B H, Mohr S, McDowell S A, et al. Differential gene expression in mesothelioma. FEBS Lett 2000;480:95-100
[15]. van de Rijn M, Perou C M, Tibshirani R, et al. Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome. Am J Pathol 2002; 161:1991-1996
[16]. Parikh H, Carlsson E, Chutkow W A, et al. TXNIP regulates peripheral glucose metabolism in humans. PLoS Med 2007;4:e158
[17]. Maas K, Chan S, Parker J, et al. Cutting edge:molecular portrait of human autoimmune disease. J Immunol 2002;169:5-9
[18]. Cardozo A K, Kruhoffer M, Leeman R, et al. Identification of novel cytokine-induced genes in pancreatic beta-cells by high-density oligonucleotide arrays. Diabetes 2001;50:909-920
[19]. Eaves I A, Wicker L S, Ghandour G, et al. Combining mouse congenic strains and microarray gene expression analyses to study a complex trait:the NOD model of type 1 diabetes. Genome Res 2002;12:232-243
[20]. Gerling I C, Singh S, Lenchik N I, et al. New data analysis and mining approaches identify unique proteome and transcriptome markers of susceptibility to autoimmune diabetes. Mol Cell Proteomics 2006;5:293-305
[21]. Gunton J E, Kulkarni R N, Yim S, et al. Loss of ARNT/HIFlbeta mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetes. Cell 2005;122:337-349
[22]. Sreekumar R, Halvatsiotis P, Schimke J C, et al. Gene expression profile in skeletal muscle of type 2 diabetes and the effect of insulin treatment. Diabetes 2002;51:1913-1920
[23]. Shalev A, Pise-Masison C A, Radonovich M, et al. Oligonucleotide microarray analysis of intact human pancreatic islets:identification of glucose-responsive genes and a highly regulated TGFbeta signaling pathway. Endocrinology 2002;143:3695-3698
[24]. Pascual V, Allantaz F, Arce E, et al. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med 2005;201:1479-1486
[25]. Basu S, Larsson A, Vessby J, et al. Type 1 diabetes is associated with increased cyclooxygenase-and cytokine-mediated inflammation. Diabetes Care 2005;28:1371-1375
[26]. Maedler K, Sergeev P, Ris F, et al. Glucose-induced beta cell production of IL-1 beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest 2002;110:851-860
[27]. Laybutt D R, Weir G C, Kaneto H, et al. Overexpression of c-Myc in beta-cells of transgenic mice causes proliferation and apoptosis, downregulation of insulin gene expression, and diabetes. Diabetes 2002;51:1793-1804
[28]. Kawasaki E, Eguchi K. Genetics of fulminant type 1 diabetes. Ann N Y Acad Sci 2006; 1079:24-30
[29]. Imagawa A, Hanafusa T. Pathogenesis of fulminant type 1 diabetes. Rev Diabet Stud 2006;3:169-177
[30]. Steppan S, Kupfer K, Mayer A, et al. Genome wide expression profiling of human peripheral blood mononuclear cells stimulated with BAY 50-4798, a novel T cell selective interleukin-2 analog. J Immunother 2007;30:150-168
[31]. Ramilo O, Allman W, Chung W, et al. Gene expression patterns in blood leukocytes discriminate patients with acute infections. Blood 2007;109:2066-2077
[32]. Bouwens M, Afman L A, Muller M. Fasting induces changes in peripheral blood mononuclear cell gene expression profiles related to increases in fatty acid beta-oxidation:functional role of peroxisome proliferator activated receptor alpha in human peripheral blood mononuclear cells. Am J Clin Nutr 2007;86:1515-1523
[33]. Tang B M, McLean A S, Dawes I W, et al. Gene-expression profiling of peripheral blood mononuclear cells in sepsis. Crit Care Med 2009;37:882-888
[34]. Chuaqui R F, Bonner R F, Best C J, et al. Post-analysis follow-up and validation of microarray experiments. Nat Genet 2002;32 Suppl:509-514
[35]. Brazma A, Hingamp P, Quackenbush J, et al. Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat Genet 2001;29:365-371
[36]. 吴斌,沈自尹.基因表达谱芯片的数据分析.世界华人消化杂志2006;14：68-74
[37]. Brazma A, Vilo J. Gene expression data analysis. Microbes Infect 2001;3:823-829
[38]. Brazma A. On the importance of standardisation in life sciences. Bioinformatics 2001;17:113-114
[39]. Radu D L. Cellular mechanisms involved in experimental insulin-dependent diabetes mellitus. Roum Arch Microbiol Immunol 2001;60:203-226
[40]. Mathis D, Vence L, Benoist C. beta-Cell death during progression to diabetes. Nature 2001;414:792-798
[41]. Muller D, Huang G C, Amiel S, et al. Identification of insulin signaling elements in human beta-cells:autocrine regulation of insulin gene expression. Diabetes 2006;55:2835-2842
[1]. Imagawa A, Hanafusa T, Miyagawa J, et al. A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies. Osaka IDDM Study Group. N Engl J Med 2000;342:301-307
[2]. Tanaka S S, T.Kobayashi,T.Momotsu. A novel subtype of type 1 diabetes mellitus. N Engl J Med 2000;342:2
[3]. Hanafusa T, Imagawa A. Fulminant type 1 diabetes:a novel clinical entity requiring special attention by all medical practitioners. Nat Clin Pract Endocrinol Metab 2007;3:36-45; quiz 32p following 69
[4]. 周智广,郑超.暴发性1型糖尿病：一种不容忽视的糖尿病急危重症.内科急危重症杂志 2008；14(4)：169-170
[5]. Imagawa A, Hanafusa T, Miyagawa J, et al. A proposal of three distinct subtypes of type 1 diabetes mellitus based on clinical and pathological evidence. Ann Med 2000;32:539-543
[6]. Katsumata K. A Chinese patient presenting with clinical signs of fulminant type 1 diabetes mellitus. Intern Med 2005;44:967-969
[7]. Jung T S, Chung S I, Kim M A, et al. A Korean patient with fulminant autoantibody-negative type 1 diabetes. Diabetes Care 2004;27:3023-3024
[8]. Taniyama M, Katsumata R, Aoki K, et al. A Filipino patient with fulminant type 1 diabetes. Diabetes Care 2004;27:842-843
[9]. 张弛,周智广,张冬梅,等.急骤起病伴胰酶升高的1型糖尿病患者临床和免疫学特征.中华医学杂志 2005;85：967-971
[10]. 周建,贾伟平,包玉倩,等.暴发性1型糖尿病合并横纹肌溶解症一例.中华内科杂志 2007；46(17)：944-945
[11]. Wang T, Xiao X H, Li W H, et al. Fulminant type 1 diabetes:report of two cases. Chin Med J (Engl) 2008;121:181-182
[12]. 陈欢欢,袁庆新,刘超.暴发性1型糖尿病1例.江苏医药 2007;33(9):969
[13]. Kawasaki E, Eguchi K. Is Type 1 diabetes in the Japanese population the same as among Caucasians? Ann N Y Acad Sci 2004;1037:96-103
[14]. Imagawa A, Hanafusa T. Fulminant type 1 diabetes-is it an Asian-oriented disease? Intern Med 2005;44:913-914
[15]. Imagawa A, Hanafusa T, Uchigata Y, et al. Fulminant type 1 diabetes:a nationwide survey in Japan. Diabetes Care 2003;26:2345-2352
[16]. Cho Y M, Kim J T, Ko K S, et al. Fulminant type 1 diabetes in Korea:high prevalence among patients with adult-onset type 1 diabetes. Diabetologia 2007;50:2276-2279
[17]. Kawasaki E, Matsuura N, Eguchi K. Type 1 diabetes in Japan. Diabetologia 2006;49:828-836
[18]. Kawasaki E, Eguchi K. Current aspects on the clinical immunology and genetics of autoimmune diabetes in Japan. Diabetes Res Clin Pract 2007;77 Suppl1:S104-109
[19]. Yamamoto N, Fujita Y, Satoh S; et al. Fulminant type 1 diabetes during pregnancy:A case report and review of the literature. J Obstet Gynaecol Res 2007;33:552-556
[20]. Shimizu I, Makino H, Osawa H, et al. Association of fulminant type 1 diabetes with pregnancy. Diabetes Res Clin Pract 2003;62:33-38
[21]. Shimizu I, Makino H, Imagawa A, et al. Clinical and immunogenetic characteristics of fulminant type 1 diabetes associated with pregnancy. J Clin Endocrinol Metab 2006;91:471-476
[22]. Seino Y, Yamauchi M, Hirai C, et al. A case of fulminant Type 1 diabetes associated with mexiletine hypersensitivity syndrome. Diabet Med 2004;21:1156-1157
[23]. Sekine N, Motokura T, Oki T, et al. Rapid loss of insulin secretion in a patient with fulminant type 1 diabetes mellitus and carbamazepine hypersensitivity syndrome. JAMA 2001;285:1153-1154
[24]. Chiou C C, Chung W H, Hung S I, et al. Fulminant type 1 diabetes mellitus caused by drug hypersensitivity syndrome with human herpesvirus 6 infection. J Am Acad Dermatol 2006;54:S14-17
[25]. Sommers L. Allopurinol hypersensitivity syndrome associated with pancreatic exocrine abnormalities and new-onset diabetes mellitus.. Arch Intern Med 2002;162:1190-1192
[26]. Hashimoto K, Yasukawa M, Tohyama M. Human herpesvirus 6 and drug allergy. Curr Opin Allergy Clin Immunol 2003;3:255-260
[27]. Takahashi J, Nishijima K, Shukunami K, et al. Flare-up of serum amylase prior to onset of lethal ketoacidosis in a patient with fulminant type 1 diabetes. Diabetes Care 2006;29:461-462
[28]. Kahara T, Takamura T, Sakurai M, et al. Pancreatic exocrine and endocrine events occur concomitantly but independently during the course of fulminant type 1 diabetes. Diabetes Res Clin Pract 2006;71:241-246
[29]. Takaike H, Uchigata Y, Iwamoto Y, et al. Nationwide survey to compare the prevalence of transient elevation of liver transaminase during treatment of diabetic ketosis or ketoacidosis in new-onset acute and fulminant type 1 diabetes mellitus. Ann Med 2008;40:395-400
[30]. Obi N, Katabami T, Asai S, et al. Fulminant type 1 diabetes complicated by leukemoid reaction. Intern Med 2008;47:847-851
[31]. Imagawa A, Hanafusa T. Fulminant type 1 diabetes mellitus. Endocr J 2006;53:577-584
[32]. Sayama K, Imagawa A, Okita K, et al. Pancreatic beta and alpha cells are both decreased in patients with fulminant type 1 diabetes:a morphometrical assessment. Diabetologia 2005;48:1560-1564
[33]. Tanaka S, Endo T, Aida K, et al. Distinct diagnostic criteria of fulminant type 1 diabetes based on serum C-peptide response and HbAlc levels at onset. Diabetes Care 2004;27:1936-1941,
[34]. 杨晓琳,周智广.暴发性1型糖尿病.中国糖尿病杂志2006；14(4)：307-308
[35]. Shield J P, Wadsworth E J, Baum J D. The genetic contribution to disease pathogenesis in childhood diabetes is greatest in the very young. Diabet Med 1995;12:377-379
[36]. Gienke R.Vreugdenhil N C S, Anne Hoorens, Ciska Rongen, Daniel G.Pipeleers,Willem J.G.Melchers, Bart O.Roep,andJochem M.D.Galama. Acute Onset of Type 1 Diabetes Mellitus after Severe Echo virus 9 Infection:PutativePathogenicPathways. Clinical Infectious Diseases 2000;31:6
[37]. Sano H, Terasaki J, Tsutsumi C, et al. A case of fulminant type 1 diabetes mellitus after influenza B infection. Diabetes Res Clin Pract 2008;79:e8-9
[38]. Goto A, Takahashi Y, Kishimoto M, et al. A case of fulminant type 1 diabetes associated with significant elevation of mumps titers. Endocr J 2008;55:561-564
[39]. Imagawa A, Hanafusa T, Makino H, et al. High titres of IgA antibodies to enterovirus in fulminant type-1 diabetes. Diabetologia 2005;48:290-293
[40]. Ylipaasto P, Klingel K, Lindberg A M, et al. Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells. Diabetologia 2004;47:225-239
[41]. Burgess J A, Kirkpatrick K L, Menser M A. Fulminant onset of diabetes mellitus during an attack of infectious mononucleosis. Med J Aust 1974;2:706-707
[42].王建平(导师：周智广).1型糖尿病胰岛自身抗体与HLA-DQ基因型的关系.[博士学位论文]长沙,中南大学,2006
[43]. Mauvais-Jarvis F, Smith S B, Le May C, et al. PAX4 gene variations predispose to ketosis-prone diabetes. Hum Mol Genet 2004;13:3151-3159
[44]. Kawasaki E, Eguchi K. Genetics of fulminant type 1 diabetes. Ann N Y Acad Sci 2006; 1079:24-30
[45]. Katahira M, Ishiguro T, Segawa S, et al. Reevaluation of Human Leukocyte Antigen DR-DQ Haplotype and Genotype in Type 1 Diabetes in the Japanese Population. Horm Res 2008;69:284-289
[46]. Imagawa A, Hanafusa T, Iwahashi H, et al. Uniformity in clinical and HLA-DR status regardless of age and gender within fulminant type 1 diabetes. Diabetes Res Clin Pract 2008
[47]. Kawasaki E, Imagawa A, Makino H, et al. Differences in the contribution of the CTLA4 gene to susceptibility to fulminant and type 1A diabetes in Japanese patients. Diabetes Care 2008;31:1608-1610
[48]. Tanaka S, Kobayashi T, Nakanishi K, et al. Association of HLA-DQ genotype in autoantibody-negative and rapid-onset type 1 diabetes. Diabetes Care 2002;25:2302-2307
[49]. Imagawa A, Hanafusa T, Uchigata Y, et al. Different contribution of class II HLA in fulminant and typical autoimmune type 1 diabetes mellitus. Diabetologia 2005;48:294-300
[50]. Wang J P, Zhou Z G, Lin J, et al. Islet autoantibodies are associated with HLA-DQ genotypes in Han Chinese patients with type 1 diabetes and their relatives. Tissue Antigens 2007;70:369-375
[51]. Jung J H, Hahm J R, Kim M A, et al. Fulminant autoantibody-negative and type 1A diabetes phenotypes in a Korean HLA identical dizygotic twin. Diabetes Care 2005;28:2330-2331
[52]. Arai T, Hashimoto H, Kawai K, et al. Fulminant type 1 diabetes mellitus observed in insulin receptor substrate 2 deficient mice. Clin Exp Med 2008;8:93-99
[53]. Nagata M, Moriyama H, Kotani R, et al. Immunological aspects of 'fulminant type 1 diabetes'. Diabetes Res Clin Pract 2007;77 Suppl 1:S99-103
[54]. Sachdeva N, Asthana D. Cytokine quantitation:technologies and applications. Front Biosci 2007; 12:4682-4695
[55]. Miura Y, Suzuki A, Sato I, et al. A case of fulminant type 1 diabetes with graves' disease. Diabetes Care 2002;25:1894-1895
[56]. Hamasaki A, Taniguchi T, Yamane S, et al. A case of fulminant type 1 diabetes associated with painless thyroiditis. Diabetes Care 2006;29:946-947
[57]. Sakaue S, Nagata M, Wakabayashi O, et al. A case of fulminant type 1 diabetes with elevated rheumatoid factor and the temporal presence of thyroid-stimulating hormone receptor antibody. Diabetes Care 2002;25:935-936
[58]. Shimada A, Morimoto J, Kodama K, et al. T-cell-mediated autoimmunity may be involved in fulminant type 1 diabetes. Diabetes Care 2002;25:635-636
[59]. Shimada A, Oikawa Y, Shigihara T, et al. A case of fulminant type 1 diabetes with strong evidence of autoimmunity. Diabetes Care 2002;25:1482-1483
[60]. Nakagawa Y, Shimada A, Oikawa Y, et al. Two cases of "fulminant" type 1 diabetes suggesting involvement of autoimmunity. Ann N Y Acad Sci 2003; 1005:359-361
[61]. Bonifacio E, Scirpoli M, Kredel K, et al. Early autoantibody responses in prediabetes are IgG1 dominated and suggest antigen-specific regulation. J Immunol 1999;163:525-532
[62]. 张冬梅,周智广,黄干,等.以自发酮症起病的新发糖尿病患者的胰岛自身抗体检测.中华全科医师杂志2005；4(5)：273-276
[63]. 王建平,周智广,黄干,等.IA-2A与GADA检测对1型糖尿病的诊断价值.中华内分泌代谢杂志2004；20(6)：494-498
[64]. Wenzlau J M, Juhl K, Yu L, et al. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci USA 2007; 104:17040-17045
[65]. Sue M, Yoshihara A, Otani T, et al. Characteristics of fulminant type 1 diabetes mellitus. Med Sci Monit 2008;14:CS97-101
[66]. Rashba E J, Reich E P, Janeway C A, et al. Type 1 diabetes mellitus:an imbalance between effector and regulatory T cells? Acta Diabetol 1993;30:61-69
[67]. Radu D L. Cellular mechanisms involved in experimental insulin-dependent diabetes mellitus. Roum Arch Microbiol Immunol 2001;60:203-226
[68]. Alyanakian M A, You S, Damotte D, et al. Diversity of regulatory CD4+T cells controlling distinct organ-specific autoimmune diseases. Proc Natl Acad Sci U S A 2003;100:15806-15811
[69]. 何凌,周智广,罗建华,等.成人隐匿性自身免疫性糖尿病患者CD4+CD25+T细胞亚群的变化.中华糖尿病杂志2005；13(6)：428-431
[70]. 李莉蓉,周智广,黄干,等.SOX13抗体对急性起病自身免疫糖尿病的诊断意义.中华内分泌代谢杂志2005；21(4)：357-360
[71]. 张翼(导师：周智广).糖尿病谷氨酸脱羧酶(GAD65)反应性T细胞的检测及应用研究.[博士学位论文]长沙,中南大学,2005
[72]. 张翼,周智广,杨琳,等.部分特发性1型糖尿病存在谷氨酸脱羧酶65反应性T细胞.中华医学杂志2007；87(16)：1102-1105
[73]. Kotani R, Nagata M, Imagawa A, et al. T lymphocyte response against pancreatic beta cell antigens in fulminant Type 1 diabetes. Diabetologia 2004;47:1285-1291
[74]. Bosi E, Minelli R, Bazzigaluppi E, et al. Fulminant autoimmune Type 1 diabetes during interferon-alpha therapy:a case of Thl-mediated disease? Diabet Med 2001;18:329-332
[75]. Aoki K, Taniyama M, Nagayama C, et al. T cell immunity to glutamic acid decarboxylase in fulminant type 1 diabetes without significant elevation of serum amylase. Ann N Y Acad Sci 2006;1079:181-185
[76]. Murase Y, Imagawa A, Hanafusa T, et al. Fulminant type 1 diabetes as a high risk group for diabetic microangiopathy--a nationwide 5-year-study in Japan. Diabetologia 2007;50:531-537
[77]. Schade D S, Eaton R P. Pathogenesis of diabetic ketoacidosis:a reappraisal. Diabetes Care 1979;2:296-306
[78]. Murase-Mishiba Y, Imagawa A, Hanafusa T. Fulminant type 1 diabetes as a model of nature to explore the role of C-peptide. Exp Diabetes Res 2008;2008:819123
[79]. Hellerstrom C, Andersson A, Gunnarsson R. Regeneration of islet cells. Acta Endocrinol Suppl (Copenh) 1976;205:145-160
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |