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Background: Association between celiac disease and type 1 diabetes in adults is still somewhat unclear, and that between celiac disease and type 2 diabetes even less known. We studied these issues in a large cohort of adult celiac disease patients.Methods: The prevalence of type 1 and type 2 diabetes in 1358 celiac patients was compared with the population-based values. Furthermore, patients with celiac disease and concomitant type 1 or type 2 diabetes and those with celiac disease only underwent comparisons of clinical and histological features and adherence to gluten-free diet.Results: The prevalence of type 1 diabetes (men/women) was 8.0 % /1.8 % in celiac patients and 0.7 % /0.3 % in the population, and that of type 2 diabetes 4.3 % /2.5 % and 4.4 % /3.0 %, respectively. Celiac patients with concomitant type 1 diabetes were younger (45 years vs 65 years and 52 years, P < 0.001) and more often screen-detected (43 % vs 13 % and 14 %, P < 0.001), had less other gastrointestinal diseases (8 % vs 40 % and 25 %, P = 0.028), more thyroidal diseases (18 % vs 16 % and 13 %, P = 0.043) and lower dietary adherence (71 % vs 95 % and 96 %, P < 0.001) compared with celiac patients with concomitant type 2 diabetes and patients with celiac disease only. Patients with concomitant type 2 diabetes had more hypercholesterolemia than the other groups (8 % vs 6 % and 4 %, P = 0.024), and both diabetes groups more hypertension (47 % and 31 % vs 15 %, P < 0.001) and coronary artery disease (29 % and 18 % vs 3 %, P < 0.001) than the patients with celiac disease only.Conclusions: Type 1 diabetes was markedly overrepresented in celiac disease, especially in men, whereas the prevalence of type 2 diabetes was comparable with the population. Concomitant type 1 or type 2 diabetes predisposes celiac patients to severe co-morbidities and type 1 diabetes also to poor dietary adherence. [ABSTRACT FROM AUTHOR]

Background: Impaired growth is a well-known complication in celiac disease, but factors associated with it are poorly known. We investigated this issue in a large cohort of children.Methods: 530 children with biopsy-proven celiac disease were included. The participants were divided into two groups on the basis of the presence (n = 182) or absence (n = 348) of growth disturbance at diagnosis. Histological, serological and clinical characteristics were compared between children with growth failure and those with normal growth. Further, patients with growth failure as the sole clinical presentation were compared to those with poor growth and concomitant other symptoms.Results: Children with growth failure were younger (p < 0.001) and had lower hemoglobin (p = 0.016) and higher celiac antibody (p < 0.001), alanine aminotransferase (p = 0.035) and thyroid-stimulating hormone values (p = 0.013) than those with normal growth. Significantly associated with growth failure at diagnosis were age <3 years (OR 4.3 (95 % CI 2.5-7.5) vs older age), diagnosis before the year 2000 and in 2000-09 (OR 3.1 (1.8-5.4) and OR 1.8 (1.1-2.8) vs diagnosis in 2010-2013), presence of total and subtotal villous atrophy (OR 4.2 (2.5-7.0) and OR 2.0 (1.3-3.2) vs partial atrophy), severe symptoms (OR 3.4 (1.8-6.7) vs mild symptoms) and vomiting (OR 3.1 (1.5-6.3). The presence of abdominal pain reduced the risk (OR 0.5 (0.3-0.7)), while there was no effect of gender, diarrhea, constipation, other chronic diseases and celiac disease in the family. Children evincing poor growth as the sole clinical presentation were older (p < 0.001) and had higher hemoglobin (P < 0.001) and total iron (p = 0.010) values and lower TG2ab values (p = 0.009) than those with growth disturbance and other symptoms.Conclusions: In particular young age and severe clinical and histological presentation were associated with growth disturbance at celiac disease diagnosis. Children with only poor growth are markedly different from those with other concomitant symptoms, suggesting different pathogenic mechanisms. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests that many coeliac disease patients suffer from persistent clinical symptoms and reduced health-related quality of life despite a strict gluten-free diet. We aimed to find predictors for these continuous health concerns in long-term treated adult coeliac patients.Methods: In a nationwide study, 596 patients filled validated Gastrointestinal Symptom Rating Scale and Psychological General Well-Being questionnaires and were interviewed regarding demographic data, clinical presentation and treatment of coeliac disease, time and place of diagnosis and presence of coeliac disease-associated or other co-morbidities. Dietary adherence was assessed by a combination of self-reported adherence and serological tests. Odds ratios and 95% confidence intervals were calculated by binary logistic regression.Results: Diagnosis at working age, long duration and severity of symptoms before diagnosis and presence of thyroidal disease, non-coeliac food intolerance or gastrointestinal co-morbidity increased the risk of persistent symptoms. Patients with extraintestinal presentation at diagnosis had fewer current symptoms than subjects with gastrointestinal manifestations. Impaired quality of life was seen in patients with long duration of symptoms before diagnosis and in those with psychiatric, neurologic or gastrointestinal co-morbidities. Patients with persistent symptoms were more likely to have reduced quality of life.Conclusions: There were a variety of factors predisposing to increased symptoms and impaired quality of life in coeliac disease. Based on our results, early diagnosis of the condition and consideration of co-morbidities may help in resolving long-lasting health problems in coeliac disease. [ABSTRACT FROM AUTHOR]

Background: Approximately 1% of the population suffer from coeliac disease. However, the disease is heavily underdiagnosed. Unexplained symptoms may lead to incremented medical consultations and productivity losses.The aim here was to estimate the possible concealed burden of untreated coeliac disease and the effects of a gluten-free diet.Methods: A nationwide cohort of 700 newly detected adult coeliac patients were prospectively evaluated. Healthcare service use and sickness absence from work during the year before diagnosis were compared with those in the general population; the data obtained from an earlier study. Additionally, the effect of one year on dietary treatment on the aforementioned parameters and on consumption of pharmaceutical agents was assessed.Results: Untreated coeliac patients used primary health care services more frequently than the general population.On a gluten-free diet, visits to primary care decreased significantly from a mean 3.6 to 2.3. The consumption of medicines for dyspepsia (from 3.7 to 2.4 pills/month) and painkillers (6.8-5.5 pills/month) and the number of antibiotic courses (0.6-0.5 prescriptions/year) was reduced. There were no changes in hospitalizations, outpatient visits to secondary and tertiary care, use of other medical services, or sickness absence, but the consumption of nutritional supplements increased on treatment.Conclusions: Coeliac disease was associated with excessive health care service use and consumption of drugs before diagnosis. Dietary treatment resulted in a diminished burden to the health care system and lower use of on-demand medicines and antibiotic treatment. The results support an augmented diagnostic approach to reduced underdiagnosis of coeliac disease.Trial registration: ClinicalTrials.gov NCT01145287 [ABSTRACT FROM AUTHOR]

Background: Association of the interleukin-23 receptor (IL23R) with inflammatory bowel disease (IBD) has been confirmed in several populations. IL23R also associates with psoriasis, suggesting that the gene may be an important candidate for many chronic inflammatory diseases. Methods: We studied association of single-nucleotide variants in IL23R with IBD in Swedish patients, in both Crohn's disease (CD) and ulcerative colitis (UC) subsets. The same genetic variants were also studied in Finnish patients with psoriasis or celiac disease, and in Hungarian and Italian patients with celiac disease. Results: Association of IL23R with IBD was replicated in our Swedish patients, and linkage and association of the IL23R region with psoriasis was found in the Finnish population. The IL23R region was also linked to celiac disease in Finnish families, but no association of IL23R variants with celiac disease was found in the Finnish, Hungarian or Italian samples. Conclusion: Our study is the first to demonstrate association of IL23R with CD and UC in Swedish patients with IBD. It is also the first study to report linkage and association of the IL23R region with psoriasis in the Finnish population. Importantly, this is the first report of linkage of the IL23R region to celiac disease, a chronic inflammatory condition in which IL23R has not been previously implicated. [ABSTRACT FROM AUTHOR]

Background: In celiac disease gluten, the disease-inducing toxic component in wheat, induces the secretion of autoantibodies which are targeted against transglutaminase 2 (TG2). These autoantibodies are produced in the smallintestinal mucosa, where they can be found deposited extracellularly below the epithelial basement membrane and around mucosal blood vessels. In addition, during gluten consumption these autoantibodies can also be detected in patients' serum but disappear from the circulation on a gluten-free diet. Interestingly, after adoption of a gluten-free diet the serum autoantibodies disappear from the circulation more rapidly than the small-intestinal mucosal autoantibody deposits. The toxicity of gluten and the secretion of the disease-specific autoantibodies have been widely studied in organ culture of small-intestinal biopsy samples, but results hitherto have been contradictory. Since the mucosal autoantibodies disappear slowly after a gluten-free diet, our aim was to establish whether autoantibody secretion to organ culture supernatants in treated celiac disease patient biopsies is related to the duration of the diet and further to the preexistence of mucosal TG2-specific IgA deposits in the cultured biopsy samples. Results: In the organ culture system conducted with biopsies derived from treated celiac disease patients, gliadin induced secretion of autoantibodies to culture supernatants, reduced epithelial cell height and increased the density of lamina proprial CD25+ cells. However, these changes could be demonstrated only in biopsies from short-term treated celiac disease patients, where the small-intestinal mucosal TG2-specific IgA autoantibody deposits were still present. Furthermore, in these biopsies autoantibody secretion could be stimulated fully only after a 48-hour gliadin challenge. Conclusion: Our results show that studies focusing on the toxic effects of gliadin in the organ culture system should be carried out with biopsy samples from short-term treated celiac disease patients who are likely still to have mucosal IgA deposits present. In addition to providing an explanation for the discrepancies in previous publications, the present study also enables further validation of the organ culture method. [ABSTRACT FROM AUTHOR]

A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide. Now we are observing another interesting phenomenon that is generating great confusion among health care professionals. The number of individuals embracing a gluten-free diet (GFD) appears much higher than the projected number of celiac disease patients, fueling a global market of gluten-free products approaching $2.5 billion (US) in global sales in 2010. This trend is supported by the notion that, along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns. This review will summarize our current knowledge about the three main forms of gluten reactions: allergic (wheat allergy), autoimmune (celiac disease, dermatitis herpetiformis and gluten ataxia) and possibly immune-mediated (gluten sensitivity), and also outline pathogenic, clinical and epidemiological differences and propose new nomenclature and classifications. [ABSTRACT FROM AUTHOR]

Background: The utility of serologic screening for celiac disease is still debatable. Evidence suggests that the disorder remains undetected even in the older population. It remains obscure whether screening makes good or harm in subjects with long-standing gluten ingestion. We evaluated whether older subjects benefit from active detection and subsequent gluten free dietary treatment of celiac disease.Methods: Thirty-five biopsy-proven patients aged over 50 years had been detected by serologic mass screening. We examined the disease history, dietary compliance, symptoms, quality of life and bone mineral density at baseline and 1-2 years after the commencement of a gluten-free diet. Symptoms were evaluated by gastrointestinal symptom rating scale and quality of life by psychological general well-being questionnaires. Small bowel biopsy, serology, laboratory parameters assessing malabsorption, and bone mineral density were investigated.Results: Dietary compliance was good. The patients had initially low mean serum ferritin values indicating subclinical iron deficiency, which was restored by a gluten-free diet. Vitamin B12, vitamin D and erythrocyte folic acid levels increased significantly on diet. Celiac patients had a history of low-energy fractures more often than the background population, and the diet had a beneficial effect on bone mineral density. Alleviation in gastrointestinal symptoms was observed, even though the patients reported no or only subtle symptoms at diagnosis. Quality of life remained unchanged. Of all the cases, two thirds would have been diagnosed even without screening if the family history, fractures or concomitant autoimmune diseases had been taken carefully into account.Conclusions: Screen-detected patients benefited from a gluten-free diet. We encourage a high index of suspicion and active case-finding in celiac disease as an alternative to mass screening in older patients. [ABSTRACT FROM AUTHOR]

Background: Due to the restrictive nature of a gluten-free diet, celiac patients are looking for alternative therapies. While drug-development programs include gluten challenges, knowledge regarding the duration of gluten challenge and gluten dosage is insufficient.We challenged adult celiac patients with gluten with a view to assessing the amount needed to cause some small-bowel mucosal deterioration.Methods: Twenty-five celiac disease adults were challenged with low (1-3 g) or moderate (3-5g) doses of gluten daily for 12 weeks. Symptoms, small-bowel morphology, densities of CD3+ intraepithelial lymphocytes (IELs) and celiac serology were determined.Results: Both moderate and low amounts of gluten induced small-bowel morphological damage in 67% of celiac patients. Moderate gluten doses also triggered mucosal inflammation and more gastrointestinal symptoms leading to premature withdrawals in seven cases. In 22% of those who developed significant small- intestinal damage, symptoms remained absent. Celiac antibodies seroconverted in 43% of the patients.Conclusions: Low amounts of gluten can also cause significant mucosal deterioration in the majority of the patients. As there are always some celiac disease patients who will not respond within these conditions, sample sizes must be sufficiently large to attain to statistical power in analysis. [ABSTRACT FROM AUTHOR]

Background: Celiac disease may emerge at any age, but little is known of its appearance in elderly people. We evaluated the prevalence of the condition in individuals over 55 years of age, and determined the incidence of biopsy-proven celiac disease (CDb) and celiac disease including seropositive subjects for anti-tissue transglutaminase antibodies (CDb+s)., Methods: The study based on prevalence figures in 2815 randomly selected subjects who had undergone a clinical examination and serologic screening for celiac disease in 2002. A second screening in the same population was carried out in 2005, comprising now 2216 individuals. Positive tissue transglutaminase antibodies were confirmed with small bowel biopsy., Results: Within three years the prevalence of CDb increased from 2.13 to 2.34%, and that of CDb+s from 2.45 to 2.70%. Five new cases were found among patients previously seronegative; two had minor abdominal symptoms and three were asymptomatic. The incidence of celiac disease in 2002-2005 was 0.23%, giving an annual incidence of 0.08% in this population., Conclusion: The prevalence of celiac disease was high in elderly people, but the symptoms were subtle. Repeated screening detected five biopsy-proven cases in three years, indicating that the disorder may develop even in the elderly. Increased alertness to the disorder is therefore warranted.

Background: The TGFbeta1-induced signal transduction processes involved in growth and differentiation are only partly known. The three-dimensional epithelial differentiation model, in which T84 epithelial cells are induced to differentiate either with TGFbeta1 or IMR-90 mesenchymal cell-secreted soluble factors, is previously shown to model epithelial cell differentiation seen in intestine. That model has not been used for large scale gene expression studies, such as microarray method. Therefore the gene expression changes were studied in undifferentiated and differentiated three-dimensional T84 cultures with cDNA microarray method in order to study the molecular changes and find new players in epithelial cell differentiation., Results: The expression of 372 genes out of 5188 arrayed sequences was significantly altered, and 47 of them were altered by both mediators. The data were validated and the altered genes are presented in ontology classes. For the genes tested the expressions in protein level were in accordance with the mRNA results. We also found 194 genes with no known function to be potentially important in epithelial cell differentiation. The mRNA expression changes induced by TGFbeta1 were bigger than changes induced by soluble factors secreted by IMR-90 mesenchymal cells. The gene expression data was depicted in already known signaling pathway routes., Conclusion: Our results reveal potential new signaling pathways and several new genes affected by TGFbeta in epithelial cell differentiation. The differentiation induced by TGFbeta1 appears to be more potent than the differentiation induced by mesenchymal cells. This study indicates that our cell culture model is a suitable tool in studying regulatory mechanisms during epithelial cell differentiation in intestine. Furthermore the present results indicate that our model is a good tool for finding new players acting in the differentiation of epithelial cells.