Accessible Requires Authentication Published by De Gruyter June 23, 2017

High prevalence of organ specific autoantibodies in Indian type 1 diabetic patients

Channabasappa Shivaprasad, Anish Kolly, Annie Pulikkal and K.M. Prasanna Kumar



Type 1 diabetes (T1D) is frequently associated with other autoimmune conditions such as autoimmune thyroiditis, coeliac disease (CD) and Addison’s disease. There are sparse data on the prevalence of antibodies against these conditions in Indian patients with T1D. This study aims to evaluate prevalence of these T1D associated autoantibodies in Indian patients.


Two hundred and fifty-eight patients with T1D were recruited from the Bangalore Diabetes Hospital and the Vydehi Institute of Medical Sciences and Research Centre (VIMS) for the study. Participants diagnosed with diabetes before the age of 18 years, as per the American Diabetes Association (ADA) criteria, and who were classified as T1D based on clinical grounds were recruited for the study. Anti-thyroid peroxidase antibody (TPO) and IgA tissue transglutaminase antibody (tTG) were estimated in all the patients. 21-Hydroxylase antibody (21-OHAb) were estimated in 170 patients. All assays were done by commercial immunoassay. Eighty-eight unrelated age-matched healthy controls were chosen for comparison.


The mean age of T1D patients was 14.33 years. The mean duration of diabetes was 4.88 years. Anti-TPO was positive in 43 (16.7%) patients with T1D as compared to 3 (3.4%) in controls. IgA tTG was positive in 12 (4.65%) patients with T1D and was absent in controls. 21-OHAb was positive in two (1.1%) patients with T1D and was absent in controls. Both patients who had positive 21-OHab had the other two antibodies. Five patients had positive anti-TPO and IgA-tTG antibodies.


Anti-TPO antibody was the most prevalent antibody in patients with T1D. Anti-TPO and IgA-tTG antibodies were significantly higher than in the control population. Further studies will be required to assess the clinical significance of these positive antibodies.

Corresponding author: Dr. Channabasappa Shivaprasad, Associate Professor, Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, 82, Nallurahalli, Whitefield, Bangalore, 560066 Karnataka, India, Phone: +91 9900021320

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


1. Barker JM. Type 1 diabetes-associated autoimmunity: natural history, genetic associations, and screening. J Clin Endocrinol Metab 2006;91:1210–7. Search in Google Scholar

2. Sridhar GR, Nagamani G. Clinical association of autoimmune diseases with diabetes mellitus: analysis from Southern India. Ann N Y Acad Sci 2002;958:390–2. Search in Google Scholar

3. Kakleas K, Soldatou A, Karachaliou F, Karavanaki K. Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus. Autoimmun Rev 2015;14:781–97. Search in Google Scholar

4. Barker JM, Yu J, Yu L, Wang J, Miao D, et al. Autoantibody “Subspecificity” in type 1 diabetes. Diabetes Care 2005;28:850–5. Search in Google Scholar

5. Umpierrez GE, Latif KA, Murphy MB, Lambeth HC, Stentz F, et al. Thyroid dysfunction in patients with type 1 diabetes: a longitudinal study. Diabetes Care 2003;26:1181–5. Search in Google Scholar

6. Denzer C, Karges B, Nake A, Rosenbauer J, Schober E, et al. Subclinical hypothyroidism and dyslipidemia in children and adolescents with type 1 diabetes mellitus. Eur J Endocrinol 2013;168:601–8. Search in Google Scholar

7. Menon PS, Vaidyanathan B, Kaur M. Autoimmune thyroid disease in Indian children with type 1 diabetes mellitus. J Pediatr Endocrinol Metab 2001;14:279–86. Search in Google Scholar

8. 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. Search in Google Scholar

9. 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. Search in Google Scholar

10. 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. Search in Google Scholar

11. Barera G, Bonfanti R, Viscardi M, Bazzigaluppi E, Calori G, et al. Occurrence of celiac disease after onset of type1 diabetes: a 6-year prospective longitudinal study. Pediatrics 2002;109:833–8. Search in Google Scholar

12. Barker JM, Ide A, Hostetler C, Yu L, Miao D, et al. Endocrine and immunogenetic testing in individuals with type 1 diabetes and 21-hydroxylase autoantibodies: addison’s disease in a high risk population. J Clin Endocrinol Metab 2005;90:128–34. Search in Google Scholar

13. Yu L, Brewer K, Gates S, Wu A, Wang T, et al. DRB1*04 and DQ alleles: expression of 21-hydroxylase autoantibodies and risk of progression to Addison’s disease. J Clin Endocrinol Metab 1999;84:328–35. Search in Google Scholar

14. Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 1997;3:797–801. Search in Google Scholar

15. Dieterich W, Laag E, Schopper H, Volta U, Ferguson A, et al. Auto- antibodies to tissue transglutaminase as predictors of celiac disease. Gastroenterology 1998;115:1317–21. Search in Google Scholar

16. Baumann-Antczak A, Wedlock N, Bednarek J, Kiso Y, Krishnan H, et al. Autoimmune Addison’s disease and 21-hydroxylase. Lancet 1992;340:429–30. Search in Google Scholar

17. Jaeger C, Hatziagelaki E, Petzoldt R, Bretzel RG. Comparative analysis of organ-specific autoantibodies and celiac disease – associated antibodies in type 1 diabetic patients, their first-degree relatives, and healthy control subjects. Diabetes Care 2001;24:27–32. Search in Google Scholar

18. Olszewska B, Michalak J, Łuczyński W, Larosa P, Chen S, et al. Organ-specific autoimmunity in relation to clinical characteristics in children with long-lasting type 1 diabetes. J Pediatr Endocrinol Metab 2016;29:647–56. Search in Google Scholar

19. 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;37:386–91. Search in Google Scholar

20. Karavanaki K, Kakleas K, Paschali E, Kefalas N, Konstantopoulos I, et al. Screening for associated autoimmunity in children and adolescents with type 1 diabetes mellitus (T1DM). Horm Res 2009;71:201–6. Search in Google Scholar

21. Kordonouri O, Klinghammer A, Lang EB, Grüters-Kieslich A, Grabert M, et al. Thyroid autoimmunity in children and adolescents with type 1 diabetes. Diabetes Care 2002;25:1346–50. Search in Google Scholar

22. Goswami R, Marwaha RK, Goswami D, Gupta N, Ray D. Prevalence of thyroid autoimmunity in sporadic idiopathic hypoparathyroidism in comparison to type 1 diabetes and premature ovarian failure. J Clin Endocrinol Metab 2006;91:4256–9. Search in Google Scholar

23. Dalbir SS, Suryanarayana KM, Kumar KM, Shivaprasad C. Thyroid function abnormalities in patients with juvenile onset type 1 diabetes. Indian J Endocr Metab 2013;17(S1):pS380. Search in Google Scholar

24. Kordonouri O, Hartmann R, Deiss D, Wilms M, Grüters-Kieslich A. Natural course of autoimmune thyroiditis in type 1 diabetes: association with gender, age, diabetes duration, and puberty. Arch Dis Child [Internet] 2005;90:411–4. Search in Google Scholar

25. Kim EY, Shin CH, Yang SW. Polymorphisms of HLA class II predispose children and adolescents with type 1 diabetes mellitus to autoimmune thyroid disease. Autoimmunity 2003;36:177–81. Search in Google Scholar

26. Sollid LM, Thorsby E. HLA susceptibility genes in celiac disease: genetic mapping and role in pathogenesis. Gastroenterology 1993;105:910–22. Search in Google Scholar

27. Fasano A, Catassi C. Celiac disease. N Engl J Med 2012;367: 2419–26. Search in Google Scholar

28. Ashabani A, Abushofa U, Abusrewill S, Abdelazez M, Tucková L, et al. The prevalence of coeliac disease in Libyan children with type 1 diabetes mellitus. Diabetes Metab Res Rev 2003;19:69–75. Search in Google Scholar

29. 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;33:453–8. Search in Google Scholar

30. Goh C, Banerjee K. Prevalence of coeliac disease in children and adolescents with type 1 diabetes mellitus in a clinic based population. Postgrad Med J 2007;83:132–6. Search in Google Scholar

31. Gabriel S, Mihaela I, Angela B, Mariana A, Doru D. Prevalence of IgA antitissue transglutaminase antibodies in children with type 1 diabetes mellitus. J Clin Lab Anal 2011;25:156–61. Search in Google Scholar

32. Kordonouri O, Dieterich W, Schuppan D, Webert G, Mullr C, et al. Autoantibodies to tissue transglutaminase are sensitive serological parameters for detecting silent coeliac disease in patients with type 1 diabetes mellitus. Diabetes Med 2000;17:441–4. Search in Google Scholar

33. Agrawal RP, Rathore A, Joshi A, Changal H, Kochar DK. Prevalence of celiac disease in type 1 diabetes mellitus in North West Rajasthan, India. Diabetes Res Clin Pract 2008;79:e15–6. Search in Google Scholar

34. Joshi R, Madvariya M. Prevalence and clinical profile of celiac disease in children with type 1 diabetes mellitus. Indian J Endocr Metab 2015;19:797–803. Search in Google Scholar

35. Jacob A, Kumar S. Celiac disease in patients with type-1 diabetes mellitus screened by tissue transglutaminase antibodies in Southern Kerala, India. Int J Nutr Wellness 2008;8:1–5. Search in Google Scholar

36. Kota SK, Meher LK, Jammula S, Kota SK, Modi KD. Clinical profile of coexisting conditions in type 1 diabetes mellitus patients. Diabetes Metab Syndr 2012;6:70–6. Search in Google Scholar

37. Bhatia E, Mehra NK, Taneja V, Vaidya MC, Ahuja MM. HLA-DR antigen frequencies in a North Indian type I diabetic population. Diabetes 1985;34:565–7. Search in Google Scholar

38. Shanmugalakshmi S, Balakrishnan K, Manoharan K, Pitchappan RM. HLA-DRB1*, -DQB1* in Piramalai Kallars and Yadhavas, two Dravidian-speaking castes of Tamil Nadu, South India. Tissue Antigens 2003;61:451–64. Search in Google Scholar

39. Dayal D, Samprati M, Kaur N, Minz RW, Jayaraman D. Prevalence of beta-cell, thyroid and celiac autoimmunity in North Indian children with recent onset type 1 diabetes (T1D). J Clin Diagn Res 2015;9:SM01–2. Search in Google Scholar

40. Lovas K, Husebye ES. High prevalence and increasing incidence of Addison’s disease in western Norway. Clin Endocrinol (Oxf) 2002;56:787–91. Search in Google Scholar

41. 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. Search in Google Scholar

42. Tandon N, Shtauvere-Brameus A, Hagopian WA, Sanjeevi CB. Prevalence of ICA-12 and other autoantibodies in North Indian patients with early-onset diabetes. Ann N Y Acad Sci 2002;958:214–7. Search in Google Scholar

43. Mohn A, Di Michele S, Di Luzio R, Tumini S, Chiarelli F. The effect of subclinical hypothyroidism on metabolic control in children and adolescents with type 1 diabetes mellitus. Diabet Med 2002;19:70–3. Search in Google Scholar

44. Iafusco D, Rea F, Prisco F. Hypoglycemia and reduction of the insulin requirement as a sign of celiac disease in children with IDDM. Diabetes Care 1998;21:1379–81. Search in Google Scholar

45. Pulikkal AA, Kolly A, Prasanna Kumar KM, Shivaprasad C. The seroprevalence of immunoglobulin A transglutaminase in type 1 diabetic patients of South Indian origin. Indian J Endocr Metab 2016;20:233–7. Search in Google Scholar

46. Likhari T, Magzoub S, Griffiths MJ, Buch HN. Screening for Addison’s disease in patients with type 1 diabetes mellitus and recurrent hypoglycaemia. Postgrad Med J 2007;83:420–1. Search in Google Scholar

47. Hügle B, Döllmann R, Keller E, Kiess W. Addison’s crisis in Adolescent patients with previously diagnosed diabetes mellitus as manifestation of polyglandular autoimmune syndrome type II – report of two patients. J Pediatr Endocrinol Metab 2011;17:93–8. Search in Google Scholar

Received: 2017-1-7
Accepted: 2017-5-9
Published Online: 2017-6-23
Published in Print: 2017-7-26

©2017 Walter de Gruyter GmbH, Berlin/Boston