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.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price includes VAT (USA)
Tax calculation will be finalised during checkout.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Dabelea D. The accelerating epidemic of childhood diabetes. Lancet. 2009;373:1999–2000. An excellent review on the increasing incidence of type 1 diabetes.
Fasano A, Catassi C. Clinical practice. Celiac disease. N Engl J Med. 2012;367:2419–26.
Kang JY, Kang AH, Green A, Gwee KA, Ho KY. Systematic review: worldwide variation in the frequency of coeliac disease and changes over time. Aliment Pharmacol Ther. 2013;38:226–45. An up-to-date review on celiac disease and worldwide variation.
Dube C, Rostom A, Sy R, Cranney A, Saloojee N, et al. The prevalence of celiac disease in average-risk and at-risk Western European populations: a systematic review. Gastroenterology. 2005;128:S57–67.
Gillett PM, Gillett HR, Israel DM, Metzger DL, Stewart L, et al. High prevalence of celiac disease in patients with type 1 diabetes detected by antibodies to endomysium and tissue transglutaminase. Can J Gastroenterol. 2001;15:297–301.
Volta U, Tovoli F, Caio G. Clinical and immunological features of celiac disease in patients with Type 1 diabetes mellitus. Expert Rev Gastroenterol Hepatol. 2011;5:479–87. A comprehensive clinical review on celiac disease in patients with type 1 diabetes.
Kaistha A, Castells S. Celiac disease in African American children with type 1 diabetes mellitus in inner city Brooklyn. Pediatr Endocrinol Rev. 2008;5 Suppl 4:994–8.
Green PH. The many faces of celiac disease: clinical presentation of celiac disease in the adult population. Gastroenterology. 2005;128:S74–8.
Reilly NR, Fasano A, Green PH. Presentation of celiac disease. Gastrointest Endosc Clin N Am. 2012;22:613–21.
Freemark M, Levitsky LL. Screening for celiac disease in children with type 1 diabetes: two views of the controversy. Diabetes Care. 2003;26:1932–9.
Holmes GK. Coeliac disease and Type 1 diabetes mellitus - the case for screening. Diabetes Med. 2001;18:169–77.
Valerio G, Maiuri L, Troncone R, Buono P, Lombardi F, et al. Severe clinical onset of diabetes and increased prevalence of other autoimmune diseases in children with coeliac disease diagnosed before diabetes mellitus. Diabetologia. 2002;45:1719–22.
Ventura A, Neri E, Ughi C, Leopaldi A, Citta A, et al. Gluten-dependent diabetes-related and thyroid-related autoantibodies in patients with celiac disease. J Pediatr. 2000;137:263–5.
Narula P, Porter L, Langton J, Rao V, Davies P, et al. Gastrointestinal symptoms in children with type 1 diabetes screened for celiac disease. Pediatrics. 2009;124:e489–95.
Cerutti F, Bruno G, Chiarelli F, Lorini R, Meschi F, et al. Younger age at onset and sex predict celiac disease in children and adolescents with type 1 diabetes: an Italian multicenter study. Diabetes Care. 2004;27:1294–8.
Camarca ME, Mozzillo E, Nugnes R, Zito E, Falco M, et al. Celiac disease in type 1 diabetes mellitus. Ital J Pediatr. 2012;38:10.
Damen GM, Boersma B, Wit JM, Heymans HS. Catch-up growth in 60 children with celiac disease. J Pediatr Gastroenterol Nutr. 1994;19:394–400.
Kordonouri O, Maguire AM, Knip M, Schober E, Lorini R, et al. ISPAD Clinical Practice Consensus Guidelines 2006-2007. Other complications and associated conditions. Pediatr Diabetes. 2007;8:171–6.
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.
Leffler DA, Schuppan D. Update on serologic testing in celiac disease. Am J Gastroenterol. 2010;105:2520–4.
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.
Rostom A, Murray JA, Kagnoff MF. American Gastroenterological Association (AGA) Institute technical review on the diagnosis and management of celiac disease. Gastroenterology. 2006;131:1981–2002.
Chand N, Mihas AA. Celiac disease: current concepts in diagnosis and treatment. J Clin Gastroenterol. 2006;40:3–14.
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.
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.
Bakker SF, Pouwer F, Tushuizen ME, Hoogma RP, Mulder CJ, et al. Compromised quality of life in patients with both Type 1 diabetes mellitus and coeliac disease. Diabetes Med. 2013;30:835–9.
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.
Leeds JS, Hopper AD, Hadjivassiliou M, Tesfaye S, Sanders DS. High prevalence of microvascular complications in adults with type 1 diabetes and newly diagnosed celiac disease. Diabetes Care. 2011;34:2158–63.
Amin R, Murphy N, Edge J, Ahmed ML, Acerini CL, et al. A longitudinal study of the effects of a gluten-free diet on glycemic control and weight gain in subjects with type 1 diabetes and celiac disease. Diabetes Care. 2002;25:1117–22.
Scaramuzza AE, Mantegazza C, Bosetti A, Zuccotti GV. Type 1 diabetes and celiac disease: the effects of gluten free diet on metabolic control. World J Diabetes. 2013;4:130–4.
Krolewski AS, Warram JH, Rand LI, Kahn CR. Epidemiologic approach to the etiology of type I diabetes mellitus and its complications. N Engl J Med. 1987;317:1390–8.
Noble JA, Erlich HA. Genetics of type 1 diabetes. Cold Spring Harb Perspect Med. 2012;2:a007732. Up-to-date review of genetic discoveries in type 1 diabetes.
Hermann R, Turpeinen H, Laine AP, Veijola R, Knip M, et al. HLA DR-DQ-encoded genetic determinants of childhood-onset type 1 diabetes in Finland: an analysis of 622 nuclear families. Tissue Antigens. 2003;62:162–9.
Sollid LM, Jabri B. Is celiac disease an autoimmune disorder? Curr Opin Immunol. 2005;17:595–600.
Kumar V, Wijmenga C, Withoff S. From genome-wide association studies to disease mechanisms: celiac disease as a model for autoimmune diseases. Semin Immunopathol. 2012;34:567–80. Recent review on genetic associations in celiac and type 1 diabetes.
Smyth DJ, Plagnol V, Walker NM, Cooper JD, Downes K, et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med. 2008;359:2767–77.
Knip M, Simell O. Environmental triggers of type 1 diabetes. Cold Spring Harb Perspect Med. 2012;2:a007690. Recent review of environmental risk factors in type 1 diabetes.
Kupfer SS, Jabri B. Pathophysiology of celiac disease. Gastrointest Endosc Clin N Am. 2012;22:639–60.
Norris JM, Barriga K, Klingensmith G, Hoffman M, Eisenbarth GS, et al. Timing of initial cereal exposure in infancy and risk of islet autoimmunity. JAMA. 2003;290:1713–20.
Ziegler AG, Schmid S, Huber D, Hummel M, Bonifacio E. Early infant feeding and risk of developing type 1 diabetes-associated autoantibodies. JAMA. 2003;290:1721–8.
Norris JM, Barriga K, Hoffenberg EJ, Taki I, Miao D, et al. Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease. JAMA. 2005;293:2343–51.
Virtanen SM, Knip M. Nutritional risk predictors of beta cell autoimmunity and type 1 diabetes at a young age. Am J Clin Nutr. 2003;78:1053–67.
Akobeng AK, Ramanan AV, Buchan I, Heller RF. Effect of breast feeding on risk of coeliac disease: a systematic review and meta-analysis of observational studies. Arch Dis Child. 2006;91:39–43.
Yeung WC, Rawlinson WD, Craig ME. Enterovirus infection and type 1 diabetes mellitus: systematic review and meta-analysis of observational molecular studies. BMJ. 2011;342:d35.
Stene LC, Oikarinen S, Hyoty H, Barriga KJ, Norris JM, et al. Enterovirus infection and progression from islet autoimmunity to type 1 diabetes: the Diabetes and Autoimmunity Study in the Young (DAISY). Diabetes. 2010;59:3174–80.
Stene LC, Honeyman MC, Hoffenberg EJ, Haas JE, Sokol RJ, et al. Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study. Am J Gastroenterol. 2006;101:2333–40.
Zanoni G, Navone R, Lunardi C, Tridente G, Bason C, et al. In celiac disease, a subset of autoantibodies against transglutaminase binds toll-like receptor 4 and induces activation of monocytes. PLoS Med. 2006;3:e358.
Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, et al. The human microbiome project. Nature. 2007;449:804–10.
Bach JF. Six questions about the hygiene hypothesis. Cell Immunol. 2005;233:158–61.
von Herrath MG, Fujinami RS, Whitton JL. Microorganisms and autoimmunity: making the barren field fertile? Nat Rev Microbiol. 2003;1:151–7.
Rook GA, Adams V, Hunt J, Palmer R, Martinelli R, et al. Mycobacteria and other environmental organisms as immunomodulators for immunoregulatory disorders. Springer Semin Immunopathol. 2004;25:237–55.
Vaarala O, Atkinson MA, Neu J. The "perfect storm" for type 1 diabetes: the complex interplay between intestinal microbiota, gut permeability, and mucosal immunity. Diabetes. 2008;57:2555–62.
Atkinson MA, Chervonsky A. Does the gut microbiota have a role in type 1 diabetes? Early evidence from humans and animal models of the disease. Diabetologia. 2012;55:2868–77. Recent review of the gut microbiome and development of type 1 diabetes.
King C, Sarvetnick N. The incidence of type-1 diabetes in NOD mice is modulated by restricted flora not germ-free conditions. PLoS One. 2011;6:e17049.
McInerney MF, Pek SB, Thomas DW. Prevention of insulitis and diabetes onset by treatment with complete Freund's adjuvant in NOD mice. Diabetes. 1991;40:715–25.
Satoh J, Shintani S, Oya K, Tanaka S, Nobunaga T, et al. Treatment with streptococcal preparation (OK-432) suppresses anti-islet autoimmunity and prevents diabetes in BB rats. Diabetes. 1988;37:1188–94.
Valladares R, Sankar D, Li N, Williams E, Lai KK, et al. Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats. PLoS One. 2010;5:e10507.
Lau K, Benitez P, Ardissone A, Wilson TD, Collins EL, et al. Inhibition of type 1 diabetes correlated to a Lactobacillus johnsonii N6.2-mediated Th17 bias. J Immunol. 2011;186:3538–46.
Markle JG, Frank DN, Mortin-Toth S, Robertson CE, Feazel LM, et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science. 2013;339:1084–88.
Lee AS, Gibson DL, Zhang Y, Sham HP, Vallance BA, et al. Gut barrier disruption by an enteric bacterial pathogen accelerates insulitis in NOD mice. Diabetologia. 2010;53:741–8.
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.
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.
Giongo A, Gano KA, Crabb DB, Mukherjee N, Novelo LL, et al. Toward defining the autoimmune microbiome for type 1 diabetes. ISME J. 2011;5:82–91.
de Goffau MC, Luopajarvi K, Knip M, Ilonen J, Ruohtula T, et al. Fecal microbiota composition differs between children with beta-cell autoimmunity and those without. Diabetes. 2013;62:1238–44.
Murri M, Leiva I, Gomez-Zumaquero JM, Tinahones FJ, Cardona F, et al. Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study. BMC Med. 2013;11:46.
Laparra JM, Olivares M, Gallina O, Sanz Y. Bifidobacterium longum CECT 7347 modulates immune responses in a gliadin-induced enteropathy animal model. PLoS One. 2012;7:e30744.
Papista C, Gerakopoulos V, Kourelis A, Sounidaki M, Kontana A, et al. Gluten induces coeliac-like disease in sensitised mice involving IgA, CD71 and transglutaminase 2 interactions that are prevented by probiotics. Lab Invest. 2012;92:625–35.
D'Arienzo R, Stefanile R, Maurano F, Mazzarella G, Ricca E, et al. Immunomodulatory effects of Lactobacillus casei administration in a mouse model of gliadin-sensitive enteropathy. Scand J Immunol. 2011;74:335–41.
Cinova J, De Palma G, Stepankova R, Kofronova O, Kverka M, et al. Role of intestinal bacteria in gliadin-induced changes in intestinal mucosa: study in germ-free rats. PLoS One. 2011;6:e16169.
Sanchez E, Donat E, Ribes-Koninckx C, Fernandez-Murga ML, Sanz Y. Duodenal-mucosal bacteria associated with celiac disease in children. Appl Environ Microbiol. 2013;79:5472–9.
Sanchez E, Ribes-Koninckx C, Calabuig M, Sanz Y. Intestinal Staphylococcus spp. and virulent features associated with coeliac disease. J Clin Pathol. 2012;65:830–4.
Collado MC, Donat E, Ribes-Koninckx C, Calabuig M, Sanz Y. Specific duodenal and faecal bacterial groups associated with paediatric coeliac disease. J Clin Pathol. 2009;62:264–9.
Nadal I, Donat E, Ribes-Koninckx C, Calabuig M, Sanz Y. Imbalance in the composition of the duodenal microbiota of children with coeliac disease. J Med Microbiol. 2007;56:1669–74.
De Palma G, Nadal I, Medina M, Donat E, Ribes-Koninckx C, et al. Intestinal dysbiosis and reduced immunoglobulin-coated bacteria associated with coeliac disease in children. BMC Microbiol. 2010;10:63.
Cheng J, Kalliomaki M, Heilig HG, Palva A, Lahteenoja H, et al. Duodenal microbiota composition and mucosal homeostasis in pediatric celiac disease. BMC Gastroenterol. 2013;13:113.
Wacklin P, Kaukinen K, Tuovinen E, Collin P, Lindfors K, et al. The duodenal microbiota composition of adult celiac disease patients is associated with the clinical manifestation of the disease. Inflamm Bowel Dis. 2013;19:934–41.
Schippa S, Iebba V, Barbato M, Di Nardo G, Totino V, et al. A distinctive 'microbial sigNature.' in celiac pediatric patients. BMC Microbiol. 2010;10:175.
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.
Sanchez E, Nadal I, Donat E, Ribes-Koninckx C, Calabuig M, et al. Reduced diversity and increased virulence-gene carriage in intestinal enterobacteria of coeliac children. BMC Gastroenterol. 2008;8:50.
Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009;139:485–98.
Gaboriau-Routhiau V, Rakotobe S, Lecuyer E, Mulder I, Lan A, et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity. 2009;31:677–89.
Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, et al. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature. 2008;455:1109–13.
Sorini C, Falcone M. Shaping the (auto)immune response in the gut: the role of intestinal immune regulation in the prevention of type 1 diabetes. Am J Clin Exp Immunol. 2013;2:156–71.
Fernandez S, Molina IJ, Romero P, Gonzalez R, Pena J, et al. Characterization of gliadin-specific Th17 cells from the mucosa of celiac disease patients. Am J Gastroenterol. 2011;106:528–38.
Boudraa G, Hachelaf W, Benbouabdellah M, Belkadi M, Benmansour FZ, et al. Prevalence of coeliac disease in diabetic children and their first- degree relatives in west Algeria: screening with serological markers. Acta Paediatr. 1996;412(Suppl):58–60.
Peretti N, Bienvenu F, Bouvet C, Fabien N, Tixier F, et al. The temporal relationship between the onset of type 1 diabetes and celiac disease: a study based on immunoglobulin a antitransglutaminase screening. Pediatrics. 2004;113:e418–22.
Mahmud FH, Murray JA, Kudva YC, Zinsmeister AR, Dierkhising RA, et al. Celiac disease in type 1 diabetes mellitus in a North American community: prevalence, serologic screening, and clinical features. Mayo Clin Proc. 2005;80:1429–34.
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.
Salardi S, Volta U, Zucchini S, Fiorini E, Maltoni G, et al. Prevalence of celiac disease in children with type 1 diabetes mellitus increased in the mid-1990s: an 18-year longitudinal study based on anti-endomysial antibodies. J Pediatr Gastroenterol Nutr. 2008;46:612–4.
Uibo O, Heilman K, Rago T, Shor R, Paal M, et al. Symptomless celiac disease in type 1 diabetes: 12-year experience in Estonia. Pediatr Int. 2010;52:230–3.
Fallahi GH, Ahmadian JH, Rabbani A, Yousefnezhad AS, Rezaei N. Screening for celiac disease in diabetic children from Iran. Indian Pediatr. 2010;47:268–70.
Djuric Z, Stamenkovic H, Stankovic T, Milicevic R, Brankovic L, et al. Celiac disease prevalence in children and adolescents with type 1 diabetes from Serbia. Pediatr Int. 2010;52:579–83.
Bhadada SK, Kochhar R, Bhansali A, Dutta U, Kumar PR, et al. Prevalence and clinical profile of celiac disease in type 1 diabetes mellitus in north India. J Gastroenterol Hepatol. 2011;26:378–81.
Hanukoglu A, Mizrachi A, Dalal I, Admoni O, Rakover Y, et al. Extrapancreatic autoimmune manifestations in type 1 diabetes patients and their first-degree relatives: a multicenter study. Diabetes Care. 2003;26:1235–40.
Sari S, Yesilkaya E, Egritas O, Bideci A, Cinaz P, et al. Prevalence of Celiac disease in Turkish children with type 1 diabetes mellitus and their non-diabetic first-degree relatives. Turk J Gastroenterol. 2010;21:34–8.
van der Windt DA, Jellema P, Mulder CJ, Kneepkens CM, van der Horst HE. Diagnostic testing for celiac disease among patients with abdominal symptoms: a systematic review. JAMA. 2010;303:1738–46. Excellent review of diagnostic testing strategies for celiac disease.
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.
This article is part of the Topical Collection on Diabetes and Other Diseases-Emerging Associations
About this article
Cite this article
Cohn, A., Sofia, A.M. & Kupfer, S.S. Type 1 Diabetes and Celiac Disease: Clinical Overlap and New Insights into Disease Pathogenesis. Curr Diab Rep 14, 517 (2014). https://doi.org/10.1007/s11892-014-0517-x
- Type 1 diabetes
- Celiac disease
- HLA genetics