Celiac disease in type 1 diabetes mellitus in the Kingdom of Saudi Arabia. Characterization and meta-analysis
Objectives: To characterize and meta-analyze the pertinent studies concerning celiac disease (CD) among patients with type 1 diabetes mellitus (T1DM) in the Kingdom of Saudi Arabia.
Methods: Data (from the relevant articles) were analyzed using both the Statistical Package for Social Sciences, version 20 (IBM Corp., Armonk, NY, USA) program and the comprehensive meta-analysis (CMA) program. This study was conducted between March and July 2018 at King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. Written ethical approval was not obtained because this study was a retrospective literature review and analysis.
Results: The prevalence of seropositive-CD was 15.88% with high heterogeneity (I2=84.0), while the prevalence of biopsy-proven CD was 12% with high heterogeneity (I2=82.7). Anti-transglutaminase was used in 7 of the 8 studies; alone in 4; with endomysial antibodies in 2; and with antigliadin antibodies (AGA) in one. In the remaining study, antireticulin antibodies was used with AGA. The age of the involved patients ranged from 8 months to 50 years old.
Conclusion: The prevalence of biopsy-proven CD among T1DM patients in Kingdom of Saudi Arabia (12.0%) was double the global prevalence (6.0%), and much higher than the normal Saudi population (1.4%). The female-to-male ratio (2:1) of CD patients in T1DM was the same as in the normal population in Kingdom of Saudi Arabia. No significant difference was detected between the reported serologically-proven rates and the reported biopsy-proven rates (p=0.093).
Saudi Med J 2019; Vol. 40 (7): 647-656
How to cite this article:
Mohammad-Ayman A. Safi. Celiac disease in type 1 diabetes mellitus in the Kingdom of Saudi Arabia: Characterization and meta-analysis. Saudi Med J 2019; 40 (7): 647-656. doi:10.15537/smj.2019.7.24293.
Payne WW. Coeliac disease and diabetes mellitus in the same patient. Great Ormond St J 1954-1955; 8: 118-122.
Walker-Smith JA, Vines R, Grigor W. Coeliac disease and diabetes. Lancet 1969; 2: 650.
Poulain C, Johanet C, Delcroix C, Lévy-Marchal C, Tubiana-Rufi N. Prevalence and clinical features of celiac disease in 950 children with type 1 diabetes in France. Diabetes Metab 2007; 33: 453-458.
Hansen D, Brock-Jacobsen B, Lund E, Bjørn C, Hansen LP, Nielsen C, et al. Clinical benefit of a gluten-free diet in type 1 diabetic children with screening-detected celiac disease: a population-based screening study with 2 years’ follow-up. Diabetes Care 2006; 29: 2452-2456.
Elfström P, Sundström J, Ludvigsson JF. Systematic review with meta-analysis: associations between coeliac disease and type 1 diabetes. Aliment Pharmacol Ther 2014; 40: 1123-1132.
Ludvigsson JF, Bai JC, Biagi F, Card TR, Ciacci C, Ciclitira PJ, et al. Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut 2014; 63: 1210-1228.
Ludvigsson JF, Ludvigsson J, Ekbom A, Montgomery SM. Celiac disease and risk of subsequent type 1 diabetes: a general population cohort study of children and adolescents. Diabetes Care 2006; 29: 2483-2488.
Safi M-AA, Safi HMA. Celiac disease and its serological pattern in Saudi Arabia: a systematic review. GVI; 2018 [Updated 2018. Accessed 2019 January 17]. Available from: https://www.oatext.com/pdf/GVI-3-133.pdf
Safi MA. Celiac disease among at-risk individuals in Saudi Arabia. Saudi Med J 2019; 40: 9-18.
Al-Ashwal AA, Shabib SM, Sakati NA, Attia NA. Prevalence and characteristics of celiac disease in type I diabetes mellitus in Saudi Arabia. Saudi Med J 2003; 24: 1113-1115.
Saadah OI, Al Agha AE, Albokhari SM, Al Mughales, JA. P0408 prevalence of celiac disease in Saudi children with type 1 diabetes mellitus JPGN; 2004 [Accessed 2019 January 17th]. Available from: https://journals.lww.com/jpgn/Fulltext/2004/06001/P0408_Prevalence_of_Celiac_Disease_in_Saudi.532.aspx
Al-Hussaini A, Sulaiman N, Al-Zahrani M, Alenizi A, El Haj I. High prevalence of celiac disease among Saudi children with type 1 diabetes: a prospective cross-sectional study. BMC Gastroenterol 2012; 12: 180.
Saadah OI, Al-Agha AE, Al Nahdi HM, Bokhary RY, Bin Talib YY, Al-Mughales JA, et al. Prevalence of celiac disease in children with type 1 diabetes mellitus screened by anti-tissue transglutaminase antibody from Western Saudi Arabia. Saudi Med J 2012; 33: 541-546.
Al-Agha AE, Alafif MM, Abd-Elhameed IA. Glycemic control, complications, and associated autoimmune diseases in children and adolescents with type 1 diabetes in Jeddah, Saudi Arabia. Saudi Med J 2015; 36: 26-31.
Alshareef MA, Aljabri KS, Bokhari SA, Al Jiffri AM, Abu Elsaoud HM, Akl AF, et al. The prevalence of celiac disease in Saudi patients with type 1 diabetes mellitus: cross sectional study. Int J Diabetes Metab Disord 2016; 1: 1-4.
Al-Hakami AM. Pattern of thyroid, celiac, and anti-cyclic citrullinated peptide autoantibodies coexistence with type 1 diabetes mellitus in patients from Southwestern Saudi Arabia. Saudi Med J 2016; 37: 386-391.
Alghamdi RA, Alghamdi AH, Fureeh AA. Sero-prevalence of celiac disease among symptom-free type 1 diabetes mellitus in Al-Baha region, Saudi Arabia. IOSR-JPBS 2018; 13: 22-26
Singh P, Arora A, Strand TA, Leffler DA, Catassi C, Green PH, et al. Global prevalence of celiac disease: systematic review and meta-analysis. Clin Gastroenterol Hepatol 2018; 16: 823-836.
Saadah OI, Al-Aama JY, Alaifan MA, Bin Talib YY, Al-Mughales JA. Prevalence of celiac disease in children with Down syndrome screened by anti-tissue transglutaminase antibodies. Saudi Med J 2012; 33: 208-210.
Saukkonen T, Savilahti E, Reijonen H, Ilonen J, Tuomilehto-Wolf E, Akerblom HK. Coeliac disease: frequent occurrence after clinical onset of insulin-dependent diabetes mellitus. Childhood diabetes in Finland study group. Diabet Med 1996; 13: 464-470.
Ventura A, Neri E, Ughi C, Leopaldi A, Città A, Not T. Gluten-dependent diabetes-related and thyroid-related autoantibodies in patients with celiac disease. J Pediatr 2000; 137: 263-265.
Sakly W, Bienvenu F, Peretti N, Lachaux A, Morel S, Bouvier R, et al. IgA anti-transglutaminase antibodies as a tool for screening atypical forms of coeliac disease in a French at-risk paediatric population. Eur J Gastroenterol Hepatol 2005; 17: 235-239.
Hansen D, Bennedbaek FN, Hansen LK, Høier-Madsen M, Hegedü LS, Jacobsen BB, et al. High prevalence of coeliac disease in Danish children with type I diabetes mellitus. Acta Paediatr 2001; 90: 1238-1243.
Fraser-Reynolds KA, Butzner JD, Stephure DK, Trussell RA, Scott RB. Use of immunoglobulin A-antiendomysial antibody to screen for celiac disease in North American children with type 1 diabetes. Diabetes Care 1998; 21: 1985-1989.
Wasertreguer S, Litwin N, Mora M. Enfermedad celı’aca asociada com diabetes mellitus insulinodependiente. Arch Arg Pediatr 1996; 94: 10-13.
Tanure MG, Silva IN, Bahia M, Penna FJ. Prevalence of celiac disease in Brazilian children with type 1 diabetes mellitus. J Pediatr Gastroenterol Nutr 2006; 42: 155-159.
Boudraa G, Hachelaf W, Benbouabdellah M, Belkadi M, Benmansour FZ, Touhami M. 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.
Cerutti F, Bruno G, Chiarelli F, Lorini R, Meschi F, Sacchetti C. 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: 1294-1298.
Kaspers S, Kordonouri O, Schober E, Grabert M, Hauffa BP, Holl RW. Anthropometry, metabolic control, and thyroid autoimmunity in type 1 diabetes with celiac disease: A multicenter survey. J Pediatr 2004; 145: 790-795.
Mankaï A, Ben Hamouda H, Amri F, Ghedira-Besbes L, Harbi A, Tahar Sfar M, et al. Screening by anti-endomysium antibodies for celiac disease in Tunisian children with type 1 diabetes mellitus. Gastroenterol Clin Biol 2007; 31: 462-466.
Ashabani A, Abushofa U, Abusrewill S, Abdelazez M, Tucková L, Tlaskalová-Hogenová H. The prevalence of coeliac disease in Libyan children with type 1 diabetes mellitus. Diabetes Metab Res Rev 2003; 19: 69-75.
Nowier SR, Eldeen NS, Farid MM, Rasol HA, Mekhemer SM. Prevalence of celiac disease among type 1 diabetic Egyptian patients and the association with autoimmune thyroid disease. Bratisl Lek Listy 2009; 110: 258-262.
Ghawil M, Miotti V, Tonutti E, Tenore A, Hadeed I, Sindici C, et al. HLA-DQ types of celiac disease in Libyan children with type 1 diabetes mellitus. Eur J Gastroenterol Hepatol 2012; 24: 59-63.
Aktay AN, Lee PC, Kumar V, Parton E, Wyatt DT, Werlin SL. The prevalence and clinical characteristics of celiac disease in juvenile diabetes in Wisconsin. J Pediatr Gastroenterol Nutr 2001; 33: 462-465.
Arató A, Körner A, Veres G, Dezsöfi A, Ujpál I, Madácsy L. Frequency of coeliac disease in Hungarian children with type 1 diabetes mellitus. Eur J Pediatr 2003; 162: 1-5.
Gillett PM, Gillett HR, Israel DM, Metzger DL, Stewart L, Chanoine JP, 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.
Not T, Tommasini A, Tonini G, Buratti E, Pocecco M, Tortul C, et al. Undiagnosed coeliac disease and risk ofautoimmune disorders in subjects with Type I diabetes mellitus. Diabetologia 2001; 44: 151-155.
Barera G, Bonfanti R, Viscardi M, Bazzigaluppi E, Calori G, Meschi F, et al. Occurrence of celiac disease after onsetof type 1 diabetes: A 6-year prospectivelongitudinal study. Pediatrics 2002; 109: 833–838.
Hansen D, Brock-Jacobsen B, Lund E, Bjørn C, Hansen LP, Nielsen C, et al. Clinical beneﬁt of a gluten-freediet in type 1 diabetic children withscreening-detected celiac disease: Apopulation-based screening study with2 years’ follow-up. Diabetes Care 2006; 29: 2452-2456.
Kabbani TA, Kelly CP, Betensky RA, Hansen J, Pallav K, Villafuerte-Gálvez JA, et al. Patients with celiac disease have a lower prevalence of non-insulin-dependent diabetes mellitus and metabolic syndrome. Gastroenterology 2013; 144: 912-917.
Safi MAA. Prevalence of celiac disease in Saudi Arabia: Metaanalysis. Global Vaccines and Immunology 2018; 3: 1-6.
Remes-Troche JM, Rios-Vaca A, Ramírez-Iglesias MT, Rubio-Tapia A, Andrade-Zarate V, Rodríguez-Vallejo F, et al. High prevalence of celiac disease in Mexican Mestizo adults with type 1 diabetes mellitus. J Clin Gastroenterol 2008; 42: 460-465.
Picarelli A, Sabbatella L, Di Tola M, Vetrano S, Casale C, Anania MC, et al. Anti-endomysial antibody of IgG1 isotype detection strongly increases the prevalence of coeliac disease in patients affected by type I diabetes mellitus. Clin Exp Immunol 2005; 142: 111-115.
Honar N, Karamizadeh Z, Saki F. Prevalence of celiac disease in patients with type 1 diabetes mellitus in the south of Iran. Turk J Gastroenterol 2013; 24: 122-126.
Leffler DA, Schuppan D. Update on serologic testing in celiac disease. Am J Gastroenterol 2010; 105: 2520-2524.
Nandiwada SL, Tebo AE. Testing for antireticulin antibodies in patients with celiac disease is obsolete: a review of recommendations for serologic screening and the literature. Clin Vaccine Immunol 2013; 20: 447-451.
Seissler J, Boms S, Wohlrab U, Morgenthaler NG, Mothes T, Boehm BO, et al. Antibodies to human recombinant tissue transglutaminase measured by radioligand assay: evidence for high diagnostic sensitivity for celiac disease. Horm Metab Res 1999; 31: 375-379.
Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 1997; 3: 797-801.
Eade OE, Lloyd RS, Lang C, Wright R. IgA and IgG reticulin antibodies in coeliac and non-coeliac patients. Gut 1977; 18: 991-993.
O’Farrelly C, Kelly J, Hekkens W, Bradley B, Thompson A, Feighery C, et al. Alpha gliadin antibody levels: a serological test for coeliac disease. Br Med J (Clin Res Ed) 1983; 286: 2007-2010.
Chorzelski TP, Beutner EH, Sulej J, Tchorzewska H, Jablonska S, Kumar V, Kapuscinska A. IgA anti-endomysium antibody. A new immunological marker of dermatitis herpetiformis and coeliac disease. Br J Dermatol 1984; 111: 395-402.
Parizade M, Bujanover Y, Weiss B, Nachmias V, Shainberg B. Performance of serology assays for diagnosing celiac disease in a clinical setting. Clin Vaccine Immunol 2009; 16: 1576-1582.
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: 567-580.
Smyth DJ, Plagnol V, Walker NM, Cooper JD, Downes K, Yang JH, et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med 2008; 359: 2767-2777.
Hermann R, Turpeinen H, Laine AP, Veijola R, Knip M, Simell O, 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: 162-169.
Sollid LM, Markussen G, Ek J, Gjerde H, Vartdal F, Thorsby E. Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer. J Exp Med 1989; 169: 345-350.
Concannon P, Rich SS, Nepom GT. Genetics of type 1A diabetes. N Engl J Med 2009; 360: 1646-1654.
Pociot F, McDermott MF. Genetics of type 1 diabetes mellitus. Genes Immun 2002; 3: 235-249.
Gutierrez-Achury J, Coutinho de Almeida R, Wijmenga C. Shared genetics in coeliac disease and other immune-mediated diseases. J Intern Med 2011; 269: 591-603.
Cotsapas C, Voight BF, Rossin E, Lage K, Neale BM, Wallace C, et al. Pervasive sharing of genetic effects in autoimmune disease. PLoS Genet 2011; 7: e1002254.
Lionetti E, Catassi C. Co-localization of gluten consumption and HLA-DQ2 and -DQ8 genotypes, a clue to the history of celiac disease. Dig Liver Dis 2014; 46: 1057-1063.
Al-Hussaini A, Alharthi H, Osman A, Eltayeb-Elsheikh N, Chentoufi A. Genetic susceptibility for celiac disease is highly prevalent in the Saudi population. Saudi J Gastroenterol 2018; 24: 268-273.
Gutierrez-Achury J, Zhernakova A, Pulit SL, Trynka G, Hunt KA, Romanos J, et al. Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease. Nat Genet 2015; 47: 577-578.
Dubois PC, Trynka G, Franke L, Hunt KA, Romanos J, Curtotti A, et al. Multiple common variants for celiac disease influencing immune gene expression. Nat Genet 2010; 42: 295-302.
Garner CP, Murray JA, Ding YC, Tien Z, van Heel DA, Neuhausen SL. Replication of celiac disease UK genome-wide association study results in a US population. Hum Mol Genet 2009; 18: 4219-4225.
Trynka G, Wijmenga C, van Heel DA. A genetic perspective on coeliac disease. Trends Mol Med 2010; 16: 537-550.
Cohn A, Sofia AM, Kupfer SS. Type 1 diabetes and celiac disease: clinical overlap and new insights into disease pathogenesis. Curr Diab Rep 2014; 14: 517.
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