Type 1 Diabetes and Celiac Disease: Clinical Overlap and New Insights into Disease Pathogenesis
- 905 Downloads
Type 1 diabetes (T1D) and celiac disease (CD) are autoimmune diseases with clinical and pathogenic overlap. The mean prevalence of CD in patients with T1D is about 8 %. Classic intestinal symptoms of CD may not be present in T1D leading to the recommendation for active case finding in this higher risk group. Screening is done with sensitive and specific serologies including tissue transglutaminase (tTG) IgA and deaminated gliadin peptide (DGP) IgA and IgG. Positive serologies are confirmed by the presence of villous atrophy and increased intraepithelial lymphocytes on duodenal biopsy. A strict gluten free diet is recommended, although this can pose challenges for T1D patients who already have dietary restrictions. In aggregate, it appears as if the gluten free diet may help T1D management. T1D and CD have overlapping genetic and environmental risk factors. Among these, non-HLA genetic factors and the gut microbiome are among recent developments that will be discussed in this review.
KeywordsType 1 diabetes Celiac disease HLA genetics Microbiome
Compliance with Ethics Guidelines
Conflict of Interest
Aaron Cohn, M. Anthony Sofia, and Sonia S. Kupfer declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 19.••Husby S, Koletzko S, Korponay-Szabo IR, Mearin ML, Phillips A, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54:136–60. Society guidelines on screening and diagnosis of celiac disease recommending screening of patients with type 1 diabetes.PubMedCrossRefGoogle Scholar
- 21.••Waisbourd-Zinman O, Hojsak I, Rosenbach Y, Mozer-Glassberg Y, Shalitin S, et al. Spontaneous normalization of anti-tissue transglutaminase antibody levels is common in children with type 1 diabetes mellitus. Dig Dis Sci. 2012;57:1314–20. Recent study that found over 30% of type 1 diabetes patients normalize celiac disease serologies while on a gluten free diet.PubMedCrossRefGoogle Scholar
- 24.Miranda J, Lasa A, Bustamante MA, Churruca I, Simon E. Nutritional differences between a gluten-free diet and a diet containing equivalent products with gluten. Plant Foods Hum Nutr. 2014;69(2):182–187.Google Scholar
- 25.••Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol. 2013;108:656–76. quiz 677. American society guidelines for screening and diagnosis of celiac disease recommending active case finding of celiac disease in individuals with type 1 diabetes.PubMedCentralPubMedCrossRefGoogle Scholar
- 27.••Mollazadegan K, Sanders DS, Ludvigsson J, Ludvigsson JF. Long-term coeliac disease influences risk of death in patients with type 1 diabetes. J Intern Med. 2013;274:273–80. This large Swedish study found with both celiac and type 1 diabetes in patients with >15 years of diabetes increases risk of death 2.8 fold.PubMedCrossRefGoogle Scholar
- 61.••Marietta EV, Gomez AM, Yeoman C, Tilahun AY, Clark CR, et al. Low incidence of spontaneous type 1 diabetes in non-obese diabetic mice raised on gluten-free diets is associated with changes in the intestinal microbiome. PLoS One. 2013;8:e78687. Marietta and colleagues compared the effect of feeding a gluten free diet and gluten containing diet on the microbiome and incidence of hyperglycemia in NOD mice and found a reduced rate of hyperglycemia while on the gluten free diet.PubMedCentralPubMedCrossRefGoogle Scholar
- 62.Soyucen E, Gulcan A, Aktuglu-Zeybek AC, Onal H, Kiykim E, et al. Differences in the gut microbiota of healthy children and those with type 1 diabetes. Pediatr Int. 2013;56(3):336–343.Google Scholar
- 78.Caminero A, Herran AR, Nistal E, Perez-Andres J, Vaquero L, et al. Diversity of the cultivable human gut microbiome involved in gluten metabolism: isolation of microorganisms with potential interest for coeliac disease. FEMS Microbiol Ecol. 2014;88(2):309–319.Google Scholar
- 88.Frohlich-Reiterer EE, Hofer S, Kaspers S, Herbst A, Kordonouri O, et al. Screening frequency for celiac disease and autoimmune thyroiditis in children and adolescents with type 1 diabetes mellitus—data from a German/Austrian multicentre survey. Pediatr Diabetes. 2008;9:546–53.PubMedCrossRefGoogle Scholar