HÜLYA ÖZDEMİR, HÜSEYİN TUFAN KUTLU, Mehmet ÖZDEMİR, Pınar İŞGÜVEN, Tülay ERKAN, Figen ÇULLU ÇOKUĞRAŞ, Sergülen DERVİŞOĞLU

Prevalence of celiac disease in children with type 1 diabetes mellitus and the accuracy of serological tests

In children with type 1 diabetes mellitus (DM), prevalence of some autoimmune diseases like celiac disease (CD) has been increased. It is also reported that CD often can be asymptomatic and only serologically evident in patients with type 1 DM. In our study, we aimed to investigate the prevalence of asymptomatic CD and the specificity and sensitivity of anti-gliadin antibodies (AGA), anti-endomysium (EMA) and tissue transglutaminase (tTG) antibodies that used for diagnosis of CD in these patients. Anti-gliadin-IgA, AGA-IgG, EMA, tTG-IgA levels were evaluated. Small-intestine biopsies were applied to the children that parents were positive for at least one of AGA-IgA, AGA IgG, EMA and tTG-IgA. A total of 268 Type 1 DM children were included in the study. Of these sixty-four children who had at least one serological positive underwent small intestine biopsies and in five children (1.9%) CD was diagnosed. Anti-endomysium and tTG-IgA positivity were detected in all cases with Celiac disease, and sensitivity was 100% for both and 95% and 86% for specificity, respectively. The sensitivity and specificity of anti-endomysium and tTG-IgA antibodies were considered to be the most reliable indicator because of their higher specificity than other serological tests. Our results, which support current guidelines, suggest that children with Type 1 DM can be screened with tTG-IgA and EMA, which are the most sensitive and specific tests to detect asymptomatic CD in these patients.

PDF

___

Barker JM. Clinical review: Type 1 diabetes-associated autoimmunity: natural history, genetic associations, and screening. J Clin Endocrinol Metab.2006;91:1210-7.

Husby S, Koletzko S, Korponay-Szabó IR, et al. ESPGHAN Working Group on Coeliac Disease Diagnosis; ESPGHAN Gastroenterology Committee; European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. ESPGHAN guidelines for the diagnosis of coeliac disease in children and adolescents. An evidence-based approach. J Pediatr Gastroenterol Nutr. 2012;54:136-60.

Ertekin V, Selimoglu MA, Doneray H, et al. Prevalence of celiac disease in a sample of Turkish children and adolescents with type 1 diabetes mellitus. J Clin Gastroenterol. 2006;40:655-7.

Tanure MG, Silva IN, Bahia M, et al. Prevalence of celiac disease in Brazilian children with type 1 diabetes mellitus. J Pediatr Gastroenterol Nutr. 2006; 42:155-9

Singh P, Seth A, Kumar P, et al. Coexistence of celiac disease & type 1 diabetes mellitus in children. Indian J Med Res. 2017;145:28-32.

Smyth DJ, Plagnol V, Walker NM, et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med. 2008;359:2767–77.

Gillett PM, Gillett HR, Israel DM, 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.

Rami B, Sumnik Z, Schober E, et al. Screening detected celiac disease in children with type 1 diabetes mellitus: Effect on the clinical course (a case control study) J Pediatr Gastroenterol Nutr. 2005;41:317–21.

Barera G, Bonfanti R, Viscardi M, et al. Occurence of celiac disease after onset of type 1 diabetes: a 6- year prospective longitudinal study. Pediatrics 2002;109:833-8.

Kordonouri O, Maguire AM, Knip M, et al. Other complications and diabetesassociated conditions in children and adolescents. Pediatr Diabetes. 2014;15 (suppl 20):270–8.

American Diabetes Association. Standards of medical care in diabetes-2015. Diabetes Care. 2015;38(supp 1):1–94.

Lazzarotto F, Basso D, Plebani M, et al. Celiac disease and type 1 diabetes. Diabetes Care. 2003;26:248-9.

Salardi S, Volta U, Zucchini S, et al. Prevalence of celiac disease in children with type 1 diabetes mellitus increased in the mid-1990’s: an 18year longitudinal study based on anti-endomysial antibodies. J Pediatr Gastroenterol Nutr. 2008;46:612–4.

Hummel M, Bonifacio E, Stern M, et al. Development of celiac diseaseassociated antibodies in offspring of parents with type I diabetes. Diabetologia. 2000;43:1005-11.

Saukkonen T, Ilonen J, Akerblom HK, et al. Prevalence of coeliac disease in siblings of patients with Type I diabetes is related to the prevalence of DQB1*02 allele. Diabetologia. 2001;44:1051-3.

Poulain C, Johanet C, Delcroix C, et al. Prevalence and clinical features of celiac disease in950 children with type 1 diabetes in France. Diabetes Metab. 2007;33:453–8.

Boudraa G, Hachelaf W, Benbouabdellah M, et al. Prevalence of coeliac disease in diabetic children and their first degree relatives in west Algeria: screening with serological markers. Acta Paediatr Suppl. 1996;412:58-60.

Hanukoglu A, Mizrachi A, Dalal I, et al. Extrapancreatic autoimmune manifestations in type 1 diabetes patients and their first-degree relatives: a multicenter study. Diabetes Care. 2003;26:1235-40.

Kang JY, Kang AH, Green A, et al. Systematic review: Worldwide variation in the frequency of coeliac disease and changes over time. Aliment Pharmacol Ther. 2013;38:226–45.

Hill ID. What are the sensitivity and specificity of serologic tests for celiac disease? Do sensitivity and specificity vary in different populations? Gastroenterology. 2005;128:25–32.

Rostom A, Dubé C, Cranney A, et al. The diagnostic accuracy of serologic tests for celiac disease: a systemic review. Gastroenterology. 2005;128:38–46.

Sugai E, Selvaggio G, Vazquez H, et al. Tissue transglutaminase antibodies in celiac disease: assessment of a commercial kit. Am J Gastroenterol. 2000;95:2318–22.

Sblattero D, Berti I, Trevisiol C, et al. Human recombinant tissue transglutaminase ELISA: an innovative diagnostic assay for celiac disease. Am J Gastroenterol. 2000;95:1253–7.

Fabiani E, Catassi C, International Working Group on Eu-tTG. The serum 19A class anti-tissue transglutaminase antibodies in the diagnosis and follow up of coeliac disease: results of an international multi-centre study. Eur J Gastroenterol Hepatol. 2001;13:659–65.

Tesei N, Sugai E, Vazquez H, et al. Antibodies to human recombinant tissue transglutaminase may detect coeliac disease patients undiagnosed by endomysial antibodies. Aliment Pharmacol Ther. 2003;17:1415–23.

Craig ME, Twigg SM, Donaghue KC, et al. Australian Type 1 Diabetes Guidelines Expert Advisory Group. National evidence-based clinical care guidelines for type 1 diabetes in children, adolescents and adults. Canberra, Australia: Australian Government Department of Health and Ageing; 2011.

Kumar V, Lerner A, Valeski JE, et al. Endomysial antibodies in the diagnosis of CD and the effect of gluten antibody titers. Immunol Invest. 1989;18:533-44.

Sugai E, Vázquez H, Nachman F, et al. Accuracy of testing for antibodies to synthetic gliadin-related peptides in celiac disease. Clin Gastroenterol Hepatol. 2006;4:1112-7.