Potential celiac disease in type 1 diabetes: a multicenter study

Aims

To describe the prevalence of potential celiac disease (pot-CD) in young patients with type 1 diabetes mellitus (T1DM) and characterize their clinical features.

Methods

This cross-sectional multicenter study involved 8717 T1DM patients from 31 Italian centers. Information was collected on the total number of T1DM patients, CD patients and pot-CD patients. The following data were collected on pot-CD patients: gender, age at T1DM diagnosis, age at the first CD serological positivity, presence of CD-related symptoms, presence of other autoimmune disorders and treatment with gluten free diet (GFD). One thousand-three-hundred-sixty-one patients who were positive for CD serology were the control group.

Results

CD serological positivity was found in 7.2% T1DM patients. Prevalence of pot-CD was 12.2% (n = 77) among CD positive patients: symptoms were present in 12/77; a third autoimmune disorder was found in 15 patients. Prevalence of pot-CD in the control population was 8.4% (n = 114; p = 0.005). No difference was found with regard to clinical features. Only few symptomatic patients were on GFD both in T1DM and control patients.

Conclusions

A higher prevalence of pot-CD was found in T1DM patients, that may be ascribed to the routine screening, although the influence of genetic factors cannot be excluded.     

Association of IFN-¹ Gene Polymorphism with Type 1 Diabetes in Iranian Patients

Background: Type 1 Diabetes (T1D) is a chronic and progressive autoimmune disorder. Cytokines play a critical role in the pathogenesis of T1D.   Objective: IFN-¹ polymorphism was investigated in T1D and compared with normal controls.   Methods: Thirty patients suffering from T1D and 40 normal controls were studied simultaneously using PCR technique. IFN-   ¹ gene was evaluated at position 5’UTR +5644. Results: There was a significant difference between patient and control groups in TT genotype (P<0.05). Conclusion: In this study, we found a negative association between IFN-¹ gene at position 5’UTR +5644 and T1D in Iranian patients pointing to T allele as a protective factor against T1D.     

Chronic Hepatitis C Virus and Celiac Disease,is there an Association?

Celiac disease (CD) has been epidemiologically associated with chronic hepatitis C (HCV), and CD activation after the initiation of interferon (IFN-α) in patients with HCV is documented. However, clear association of CD and HCV is lacking. A prospectively maintained database of 878 CD patients showed a prevalence of 0.68% (six patients). Symptoms of diarrhea, weight loss, and depression prompted the diagnosis of CD during or after IFN-α therapy in four cases. Also, 294 subjects with liver disease (195 with HCV, 80 normal controls and 19 disease controls) were prospectively screened for CD. The mean age of the subjects was 50.1 years (SD 12.3), 58% males:42% females. A total of 30% received IFN-α therapy (16% at the time of testing for CD). Two HCV patients (1%) had positive tTG-IgA but these had negative endomysial antibody (EMA) and normal duodenal biopsies. CD prevalence is not increased in patients with HCV. Routine screening of CD in HCV patients is not warranted, however, the presence of CD should be considered in the setting of clinical deterioration during or after IFN-α therapy.     

Anti-transglutaminase IgA ELISA: Clinical Potential and Drawbacks in Celiac Disease Diagnosis

Background: Since the identification of tissue transglutaminase (tTG) as the antigen for the antiendomysial antibodies (EMA), several antigen-specific immunoassays have been reported for celiac disease (CD) screening. A first objective was to evaluate the suitability for CD screening of three different IgA tTG ELISAs, two of them based on guinea pig liver tTG (gp-tTG) (an in-house ELISA with a partially purified extract and a commercial ELISA with purified gp-tTG antigen) and a third recombinant human tTG (rh-tTG) ELISA. The results are compared with EMA and with the final clinical diagnosis. A second objective was to analyze antibody reactivities in those patients with anti-tTG and EMA discrepancies. Methods: ELISA and EMA tests were used to measure IgA anti-tTG levels in sera from 259 patients (107 had CD and 72 had Type I diabetes mellitus). Results: The purified gp-tTG ELISA was highly sensitive (97.7%) and specific (98.8%) in the detection of CD, almost equaling EMA. Rh-tTG ELISA did not improved the sensitivity of EMA, but its specificity was slightly superior. Immunoblot analysis with partially purified gp-tTG extract, the antigen most frequently used for anti-tTG detection, showed that the majority of false positives were due to IgA reactivities to contaminant proteins present in the liver antigenic extract. This low specificity was particularly problematic in diabetics. Conclusion: Purified tTG ELISAs, either with purified guinea pig liver or recombinant human antigens, can be used as quantitative and observer-independent alternatives to the traditional and time-consuming EMA in the screening of CD.     

1型糖尿病与卒中

多项研究显示,1型糖尿病(type l diabetes mellitus,T1DM)的发病率正在以每年2％～5％增高.与2型糖尿病一样,T1DM也是卒中的危险因素.尽管一些T1DM研究将卒中作为心血管事件复合终点的组成部分,但很少有研究专注于T1DM患者的卒中风险.最近的研究显示,T1 DM患者的卒中风险显著高于无糖尿病者,特别是在50岁以下人群中.此外,TIDM患者死于卒中的风险较普通人群增高3～4倍.文章对T1DM与卒中的关系进行了综述.     

1型糖尿病患者血浆microRNA-126 变化与内皮功能的相关性

目的 探讨1型糖尿病患者血浆microRNA-126表达水平的变化及其临床意义,并分析microRNA-126与内皮功能的关系。方法 采用实时荧光定量聚合酶链反应检测47例1型糖尿病患者及50例健康对照组人群血浆microRNA-126的表达水平,酶联免疫吸附法检测人内皮型一氧化氮合酶（eNOS）含量,分析血浆microRNA-126表达水平与人内皮型一氧化氮合酶含量的相关性。结果 与健康对照组相比,1型糖尿病组血浆microRNA-126表达水平明显下降（P<0.05）,人内皮型一氧化氮合酶含量也明显下降（P<0.05）。相关分析显示血浆microRNA-126表达水平与人内皮型一氧化氮合酶含量呈明显正相关（P<0.05）。结论 1型糖尿病患者血浆microRNA-126水平呈低表达,而糖尿病患者常伴有内皮功能损伤,提示microRNA-126的下调可能与内皮损伤有关。microRNA-126可能通过介导内皮功能的损伤而参与1型糖尿病血管并发症的发生发展。     

Relevance of Target-Organ Lesions as Predictors of Mortality in Patients with Diabetes Mellitus

Background

Patients with diabetes are in extract higher risk for fatal cardiovascular events.

Objective

To evaluate major predictors of mortality in subjects with type 2 diabetes.

Methods

A cohort of 323 individuals with type 2 diabetes from several regions of Brazil was followed for a long period. Baseline electrocardiograms, clinical and laboratory data obtained were used to determine hazard ratios (HR) and confidence interval (CI) related to cardiovascular and total mortality.

Results

After 9.2 years of follow-up (median), 33 subjects died (17 from cardiovascular causes). Cardiovascular mortality was associated with male gender; smoking; prior myocardial infarction; long QTc interval; left ventricular hypertrophy; and eGFR <60 mL/min. These factors, in addition to obesity, were predictors of total mortality. Cardiovascular mortality was adjusted for age and gender, but remained associated with: smoking (HR = 3.8; 95% CI 1.3-11.8; p = 0.019); prior myocardial infarction (HR = 8.5; 95% CI 1.8-39.9; p = 0.007); eGFR < 60 mL/min (HR = 9.5; 95% CI 2.7-33.7; p = 0.001); long QTc interval (HR = 5.1; 95% CI 1.7-15.2; p = 0.004); and left ventricular hypertrophy (HR = 3.5; 95% CI 1.3-9.7; p = 0.002). Total mortality was associated with obesity (HR = 2.3; 95% CI 1.1-5.1; p = 0.030); smoking (HR = 2.5; 95% CI 1.0-6.1; p = 0.046); prior myocardial infarction (HR = 3.1; 95% CI 1.4-6.1; p = 0.005), and long QTc interval (HR = 3.1; 95% CI 1.4-6.1; p = 0.017).

Conclusions

Biomarkers of simple measurement, particularly those related to target-organ lesions, were predictors of mortality in subjects with type 2 diabetes.     

GLP-1及受体激动剂联合间充质干细胞对1型糖尿病胰岛β细胞的保护作用

1型糖尿病(type1diabetes Mellitus,T1DM)由于自身免疫介导引起胰岛β细胞破坏、凋亡增加,同时α细胞功能失调,不恰当分泌胰高血糖素,进一步加重高血糖.因而,早期诱导免疫耐受,刺激β细胞再生,抑制α细胞分泌胰高血糖素,将是治疗T1DM关键.目前T1DM除药物治疗外,由于间充质干细胞(mesenchymalstemcells,MSCs)能分泌抗炎和免疫调节因子,诱导免疫耐受,抑制T细胞的增殖,趋化并修复受损伤组织;同时分泌多种营养因子,促进β细胞增殖分化,从而治疗糖尿病.但MSCs治疗后胰岛β细胞增生的同时,α细胞也出现了不同程度的增生.胰高血糖素样肽1(glucagon-likepeptide1,GLP-1)及受体激动剂能抑制α细胞分泌胰高血糖素,且有一定的促进胰岛β细胞增殖及再生,抑制β细胞凋亡,诱导干细胞向胰岛素分泌细胞分化的能力.两者联用,对胰岛β细胞保护方面具有协同作用.     

Immunoreactivity of Antibodies Against Transglutaminase-Deamidated Gliadins in Adult Celiac Disease

Background The significance of the presence of anti-gliadin antibodies in patients affected by celiac disease is still unclear. It is hypothesized that gliadin deamidation, catalysed by transglutaminase, plays a role in favoring the antigen presentation. Aim To determine the immunoreactivity of anti-gliadin antibodies from untreated celiac patients to transglutaminase deamidated gliadins. Materials and methods Gliadins from wheat flour underwent enzymatic digestion and were deamidated or cysteamine-transamidated by transglutaminase. Immunoreactivity of anti-gliadin antibodies from untreated adult celiac patients sera was evaluated by means of a competitive enzyme-linked immunosorbent assay (ELISA) method. Results Gliadin deamidation increased antibodies immunoreactivity from 25% to 50% while cysteamine incorporation into the gliadin peptides resulted in an immunoreactivity decrease. Conclusions Increased immunoreactivity of transglutaminase deamidated gliadins tested with anti-gliadin antibodies from untreated adult celiac patients supports the hypothesis of a pivotal role of gliadin deamidation in the pathomechanism of celiac disease.     

为什么要下调空腹血糖受损的下限切点?

20 0 3年 11月 ,美国糖尿病协会糖尿病诊断分型专家委员会提出空腹血糖受损 (IFG)下限诊断标准切割点从 6.1mmol/L下调到 5 .6mmol/L ,而上限诊断点 7.0mmol/L保持不变。国内流行病学资料分析结果显示 ,此建议同样适合于中国人群。IFG下限诊断点下调到 5 .6mmol/L后 ,扩大了糖尿病的高危人群 ,对糖尿病及心血管并发症的防治可能具有重大的意义     

他汀类药物治疗与新发糖尿病

他汀类药物是一类可有效降低包括心肌梗死和卒中在内的心血管事件风险的降胆固醇药.临床试验和汇总分析均表明,他汀类药物治疗可增高新发糖尿病风险.文章对他汀类药物诱发糖尿病的证据、可能机制和临床意义进行了综述.     

Deamidation of Gliadin Peptides in Lamina Propria: Implications for Celiac Disease

Activation of small intestinal gluten-reactive CD4⁺ T-cells is a critical event in celiac disease. Deamidation of specific glutamine residues by tissue transglutaminase enhances the binding of T-cell activating gliadin epitopes to DQ2, increasing T-cell recognition. Our purpose was to investigate whether deamidated gliadin epitopes can be generated in the small intestinal mucosa by tissue transglutaminase and to characterize the location of the process. Intestinal explants from pig intestine and frozen biopsy slices from human and rat intestine were incubated with α-gliadin peptides containing the immunodominant motif. Monoclonal antibodies specifically recognizing the non-deamidated and/or the deamidated epitope were used for immunofluorescence studies. We conclude that endogenous tissue transglutaminase can mediate extracellular deamidation of gliadin peptides in the lamina propria. Gliadin peptides with more than one recognition site can be simultaneously cross-linked and deamidated extracellularly in the lamina propria, and might be of importance for the antibody response seen in untreated celiac disease patients.     

儿童1型糖尿病合并自身免疫性甲状腺疾病12例临床分析

目的 分析儿童1型糖尿病(T1DM)合并自身免疫甲状腺疾病(AITD)对T1DM治疗的影响。方法 1993～2002年在我院诊治的T1DM患儿合并甲状腺疾病者12例。对患儿的病史、家族史、体格检查及内分泌相关检查的结果进行分析。抗体检查：GAD-Ab、IAA、ICA、TG-Ab、TPO-Ab、TRAb和肾上腺皮质细胞浆抗体(ACC)。采用t检验将T1DM合并Graves病(GD)与合并桥本甲状腺炎(HT)者进行糖化血红蛋白(HbA1c)和胰岛素用量的分组比较；采用秩和检验对病程进行比较。结果 该组儿童患GD和HT者，分别为4例和8例。T1DM和AITD发病间隔为0～10年；GD的临床表现可不突出。有内分泌家族史者占25％。GD控制前患儿的HbA1c分别为10％、12％和14％，1例结束GD疗程者的HbA1c为7．8％。合并HT者的糖尿病代谢控制相对较好，HbA1c为7．2％～10％，1例新诊断T1DM合并HT且尚未治疗HT的患儿，HbA1c为6．3％。经t检验显示两组患儿的HbA1c差异有显著意义(P=0．011)，而病程和胰岛素用量差异无显著意义。结论该组患儿女性多于男性；HT患儿较GD患儿为多；有较强的内分泌疾病家族史。AITD影响糖尿病控制。T1DM患儿宜定期进行甲状腺自身抗体和甲状腺功能检查。     

Adult celiac disease with acetylcholine receptor antibody positive myasthenia gravis

Celiac disease has been associated with some autoimmune disorders. A 40-year-old competitive strongman with celiac disease responded to a glutenfree diet, but developed profound and generalized motor weakness with acetylcholine receptor antibody positive myasthenia gravis, a disorder reported to occur in about 1 in 5000. This possible relationship between myasthenia gravis and celiac disease was further explored in serological studies. Frozen stored serum samples from 23 acetylcholine receptor antibody positive myasthenia gravis patients with no intestinal symptoms were used to screen for celiac disease. Both endomysial and tissue transglutaminase antibodies were examined. One of 23 （or, about 4.3%） was positive for both IgA-endomysial and IgA tissue transglutaminase antibodies. Endoscopic studies subsequently showed duodenal mucosal scalloping and biopsies confirmed the histopathological changes of celiac disease. Celiac disease and myasthenia gravis may occur together more often than is currently appreciated. The presence of motor weakness in celiac disease may be a clue to occult myasthenia gravis, even in the absence of intestinal symptoms.     

2型糖尿病患者的颈动脉内膜-中膜厚度

糖尿病相关大血管疾病是2型糖尿病的主要威胁,其主要病理学机制是动脉粥样硬化.利用高分辨率超声技术检测颈动脉内膜-中膜厚度(carotid intima-media thickness,CIMT)作为亚临床动脉粥样硬化的替代指标,业已证实其为心脑血管病的强烈预测因素.文章将着重阐述2型糖尿病患者CIMT相关危险因素的最新研究进展.     

Celiac disease in a rheumatology unit: a case study

The objective of the study is to present a series of 20 patients who have been attending a rheumatology unit and were diagnosed with celiac disease in adult life. The record-charts of 20 Italian not consanguineous patients affected by celiac disease (1 man and 19 women, mean age of 46.7), diagnosed at >16 years of age, followed by a rheumatology unit were reviewed (group 1). Any other autoimmune disease diagnosed in the patients were given was recorded; moreover, the reason for rheumatologist evaluation was registered as well as the presence of symptoms suggestive of celiac disease and the obstetric history. The clinical features were compared with those of a group of 40 celiac patients (8 men and 32 women, mean age of 43.1) followed by a medicine department (group 2); even in these cases the diagnosis of celiac disease was performed in adult life. Sixteen out of 20 patients in Group 1 were diagnosed as suffering from celiac disease by the rheumatologist. Seventeen concomitant autoimmune disorders among which nine were connective tissue diseases were found in 15 patients. The main reason for rheumatologist evaluation was arthromyalgias. Ten patients showed one or more clinical features suggestive of celiac disease; moreover, eight patients had a history of sideropenic anemia. After the adoption of a gluten-free diet there were three pregnancies that all ended with alive newborns, differently from the obstetric history before celiac disease diagnosis, characterized by a relevant number of miscarriages and foetus deaths. In Group 2, a total of ten autoimmune diseases concomitant with celiac disease were found in eight patients; autoimmune thyroid disorders represented the most frequent cases. No connective tissue diseases were recognized. Celiac disease may coexist with connective tissue diseases; the recognition of this association is difficult because celiac disease may present with atypical or even symptomless forms or in some cases may resemble a multisystem disorder or may mimic a rheumatologic condition; on the other hand, the variety of symptoms of rheumatic disorders may make difficult the diagnosis of celiac disease in association with a systemic autoimmune disease. These confounding factors often lead to a delay in performing the right diagnostic formulation.