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Urinary nitric oxide metabolites in children with celiac disease after long-term consumption of oats-containing gluten-free diet
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
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2014 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, no 11, 1311-1317 p.Article in journal (Refereed) Published
Abstract [en]

Objective. Oats are accepted in the gluten-free diet (GFD) for children with celiac disease (CD). Some reports have indicated, however, that not all celiac patients tolerate oats. We have previously shown that some children still have high levels of urinary nitric oxide (NO) metabolites as markers of intestinal inflammation after 1 year on GFD with oats. In this study, we measured urinary NO metabolites in CD children who had been consuming oats-containing GFD for an extended, 2-6-year period, also taking into consideration ordinary consumption of nitrite/nitrate-rich foods close to the urine sampling. Materials and Methods. Morning urinary nitrite/nitrate concentrations were measured in 188 pediatric CD patients. A questionnaire was used to elucidate factors possibly affecting the urinary levels, for example, dietary factors, asthma, or urinary tract infection. Results. Oats were consumed by 89.4% of the patients for a median time of 3 years. The median nitrite/nitrate level was 980 mu M. The majority (70.2%) who consumed oats had low levels of urinary nitrite/nitrate, that is, less than 1400 mu M, while 29.8% demonstrated high levels, that is, greater than 1400 mu M. Nitrite/nitrate-rich foods did not significantly influence the urinary concentrations. Conclusion. The urinary levels of NO metabolites revealed two subpopulations, one with high and one with low levels. The high levels could be possibly due to poor adherence to the GFD, sensitivity to oats, or some unknown factor(s). Nitrate-rich foods, asthma, or urinary tract infection did not affect the result. The elevated levels of NO metabolites could indicate mucosal inflammation and pinpoint the need of careful follow-up of children on oats-containing GFD.

Place, publisher, year, edition, pages
Informa Healthcare , 2014. Vol. 49, no 11, 1311-1317 p.
Keyword [en]
celiac disease; gluten-free diet; oats; urinary nitrite/nitrate
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-113064DOI: 10.3109/00365521.2014.946081ISI: 000345603400006PubMedID: 25263796OAI: oai:DiVA.org:liu-113064DiVA: diva2:778260
Note

Funding Agencies|Medical Research Council of Southeast Sweden; County Council of Ostergotland; Swedish Research Council

Available from: 2015-01-09 Created: 2015-01-08 Last updated: 2017-12-05
In thesis
1. Demographics, clinical features and treatment of pediatric celiac disease
Open this publication in new window or tab >>Demographics, clinical features and treatment of pediatric celiac disease
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Celiac disease (CD) is a chronic small intestinal immune-mediated enteropathy triggered by ingestion of gluten-containing food in genetically predisposed subjects. The enteropathy is presented with a wide variety of clinical manifestations, which can occur even outside the gastrointestinal tract. In the majority of cases, the diagnosis of CD is based on a small intestinal biopsy showing mucosal alterations, i.e. intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy. The treatment, gluten-free diet (GFD), has recently been revised with the addition of gluten-free oats. Oats give a more diversified nutrition and increase the fibre content. The use of oats in CD is though still debated in some reports. A strict life-long adherence to the GFD can be problematic, especially for pediatric CD patients. Sweden reported of one of the highest observed CD prevalences worldwide, i.e. 3%, among 12-year-olds born during what has been described as “the Swedish celiac epidemic”, 1984−1996.

The aims of this thesis were to elucidate how pediatric CD has changed during a 41-year period in Sweden, i.e. 1973−2013, in terms of clinical presentation, disease severity, incidence, and demographics. We also wanted to adress the compliance to the GFD, the use of oats in the GFD and the safety of oats inclusion in the diet by measuring urinary nitric oxide (NO) metabolites.

Filed information provided data about 2856 pediatric patients  investigated for suspected CD between 1973 and 2013; of which 1030 patients were diagnosed with CD. After the data analyses the mean age of CD patients was shown to increase after the celiac epidemic period. Currently, CD shows a less severe picture in terms of symptoms and intestinal pathology. Younger children suffer primarily from gastrointestinal symptoms and growth failure, whereas extra-intestinal manifestations are more often displayed among adolescents.

We also reported an unusually high pediatric CD incidence rate and  cumulative incidence, likely the highest reported worldwide. We hypothesised that the introduction of new antibody tests would affect the diagnostic activity and accuracy in performing small intestinal biopsies for CD investigation. However, the outcome of diagnostic activity and accuracy could not clearly be attributed to the use of antibody tests due to changes occurring in parallel during the 41-year study period, e.g. a different pattern of symptoms at presentation and improved knowledge of the disease among parents and health professionals.

In a questionnaire-based study our patient group reported a high  compliance to the GFD. Long duration of the GFD may, however, influence compliance negatively. Oats have been included to the GFD of our study population in most of the cases without reporting major complications related to their well-being.

The urinary measurements of NO metabolites revealed two patient groups, one with high and one with low levels. The two populations did not differ regarding sex, age, compliance to the GFD or oats consumption. Factors such as nitrate-rich foods, asthma or urinary tract infections did not affect the results. The high levels could possibly be attributed to poor adherence to the GFD, sensitivity to oats, or some unknown factor(s). The elevated levels of NO metabolites might indicate mucosal inflammation and pinpoint the need of careful follow-up of children on oats-containing GFD as not all of them might tolerate oats.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. 76 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1473
National Category
Pediatrics Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-122371 (URN)10.3384/diss.diva-122371 (DOI)978-91-7685-977-3 (ISBN)
Public defence
2015-11-19, Linden, ing 65 pl 9, Campus US, Linköping, 13:00 (English)
Opponent
Supervisors
Funder
Region ÖstergötlandMedical Research Council of Southeast Sweden (FORSS)Region ÖstergötlandSwedish Research Council
Available from: 2015-10-30 Created: 2015-10-30 Last updated: 2015-10-30Bibliographically approved

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Tapsas, DimitriosFälth-Magnusson, KarinHögberg, LottaForslund, TonySundqvist, TommyHollén, Elisabet

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Tapsas, DimitriosFälth-Magnusson, KarinHögberg, LottaForslund, TonySundqvist, TommyHollén, Elisabet
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Division of Clinical SciencesFaculty of Health SciencesDepartment of Paediatrics in LinköpingDepartment of Paediatrics in NorrköpingDivision of Microbiology and Molecular Medicine
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