Skip to main content

Advertisement

Log in

Islet, thyroid and transglutaminase antibodies in adult Bulgarian patients with type 1 diabetes

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Aim

The aim of the study was to assess the prevalence and relationship of islet antibodies and autoantibodies of the most common associated autoimmune diseases—autoimmune thyroid disease (AITD) and celiac disease, in adult Bulgarian patients with type 1 diabetes of short duration.

Material and methods

160 type 1 diabetes patients, of mean age 36.3 ± 10.9 years, mean BMI 23.0 ± 4.2 kg/m2 and mean disease duration 1.35 ± 1.69 years were enrolled. Pancreatic islet cell antibodies—glutamic acid decarboxylase antibodies (GAD 65-Ab), tyrosine phosphatase antibodies (IA 2-Ab), and zinc transporter 8 antibodies (ZnT8-Ab), thyroid antibodies—thyroperoxidase and thyroglobulin antibodies, and transglutaminase antibodies (TTG-IgA-Ab) were assessed by ELISA.

Results

87.5% of the patients had one or more of the islet antibodies—78.1% had GAD 65-Ab, 53.1%—ZnT8-Ab, and 34.4%—IA 2-Ab. 5% presented as just ZnT8-Ab positive. GAD 65-Ab identified 90.6% of the antibody positive patients. The addition of IA 2-Ab as a second immunologic marker identified 94.4%, while the use of ZnT8-Ab in second place identified 98.8% of the cases. 24.4% presented with positive thyroid antibodies and 33.8% had AITD. No relation was found between any of the islet antibodies and AITD. None of the patients was TTG-IgA-Ab positive. No significant correlations were established between the antibodies with different organ specificity.

Conclusions

In adult Bulgarian type 1 diabetes patients ZnT8-Ab is an independent diagnostic marker rating second in prevalence and diagnostic significance after GAD 65-Ab. AITD affects about one third of this population and routine screening is required, while screening for celiac disease is not justified.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. M.P. Morran, A. Vonberg, A. Khadra, M. Pietropaolo, Immunogenetics of type 1 diabetes mellitus. Mol. Aspects Med. 42, 42–60 (2015)

    Article  CAS  Google Scholar 

  2. American Diabetes Association: 2., Classification and diagnosis of diabetes: standards of medical care in diabetes - 2020. Diabetes Care 43(Suppl. 1), S14–S31 (2020)

    Article  Google Scholar 

  3. M.J. Gan, A. Albanese-O’Neill, M.J. Haller, Type 1 diabetes: current concepts in epidemiology, pathophysiology, clinical care, and research. Curr. Probl. Pediatr. Adolesc. Health Care 42(10), 269–291 (2012)

    Article  Google Scholar 

  4. C. Pihoker, L.K. Gilliam, C.S. Hampe, A. Lernmark, Autoantibodies in diabetes. Diabetes 54(suppl 2), S52–S61 (2005)

    Article  CAS  Google Scholar 

  5. J.M. Wenzlau, K. Juhl, L. Yu, O. Moua, S.A. Sarkar, P. Gottlieb et al. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc. Natl. Acad. Sci. USA 104(43), 17040–17045 (2007)

    Article  CAS  Google Scholar 

  6. K. Kakleas, A. Soldatoua, F. Karachalioub, K. Karavanakia, Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus (T1DM). Autoimmunity Rev. 14(9), 781–797 (2015)

    Article  CAS  Google Scholar 

  7. I. Vermeulen, I. Weets, M. Asanghanwa, J. Ruige, L. Van Gaal, C. Mathieu, B. Keymeulen, V. Lampasona, J.M. Wenzlau, J.C. Hutton, D.G. Pipeleers, F.K. Gorus, The Belgian Diabetes Registry, Contribution of antibodies against IA-2β and zinc transporter 8 to classification of diabetes diagnosed under 40 years of age. Diabetes Care 34(8), 1760–1765 (2011)

  8. C. Nederstigt, B.S. Uitbeijerse, L.G.M. Janssen, E.P.M. Corssmit, E.J.P. de Koning, O.M. Dekkers, Associated auto-immune disease in type 1 diabetes patients: a systematic review and meta-analysis. Eur. J. Endocrinol. 180(2), 135–144 (2019)

    Article  CAS  Google Scholar 

  9. American Diabetes Association: 4., Comprehensive medical evaluation and assessment of comorbidities: standards of medical care in diabetes—2020. Diabetes Care 43(Suppl.1), S37–S47 (2020)

    Article  Google Scholar 

  10. American Diabetes Association: 13., Children and adolescents: standards of medical care in diabetes 2019. Diabetes Care 42(Suppl.1), S148–S164 (2020)

    Google Scholar 

  11. American Diabetes Association: 4., Comprehensive medical evaluation and assessment of comorbidities: standards of medical care in diabetes-2019. Diabetes Care 42(Supplement 1), S34–S45 (2019)

    Article  Google Scholar 

  12. C. Tiberti, R. Buzzetti, E. Anastasi, F. Dotta, M. Vasta, A. Petrone, M. Cervoni, P. Torresi, E. Vecci, G. Multari, U. Di Mario, Autoantibody negative new onset type 1 diabetic patients lacking high risk HLA alleles in a caucasian population: are these type 1b diabetes cases? Diabetes Metab. Res. Rev. 16(1), 8–14 (2000)

    Article  CAS  Google Scholar 

  13. Wenzlau, J.: Zinc transporter 8 (ZnT8) autoantibodies Diapedia 2105812817 rev. no. 9. (2016), https://doi.org/10.14496/dia.2105812817.9

  14. E. Kawasaki, Type 1 diabetes and autoimmunity. Clin. Pediatr. Endocrinol. 23(4), 99–105 (2014)

    Article  Google Scholar 

  15. L. Yang, S. Luo, G. Huang, J. Peng, X. Li, X. Yan et al. The diagnostic value of zinc transporter 8 autoantibody (ZnT8A) for type 1 diabetes in Chinese. Diabetes Metab. Res. Rev. 26(7), 579–584 (2010)

    Article  CAS  Google Scholar 

  16. E. Kawasaki, K. Nakamura, G. Kuriya, T. Satoh, M. Kobayashi, H. Kuwahara et al. Differences in the humoral autoreactivity to zinc transporter 8 between childhood- and adult-onset type 1 diabetes in Japanese patients. Clin. Immunol. 138(2), 146–153 (2011)

    Article  CAS  Google Scholar 

  17. C. Andersson, K. Larsson, F. Vaziri-Sani, K. Lynch, A. Carlsson, E. Cedervall et al. The three ZNT8 autoantibody variants together improve the diagnostic sensitivity of childhood and adolescent type 1 diabetes. Autoimmunity 44(5), 394–405 (2011)

    Article  CAS  Google Scholar 

  18. C. Andersson, F. Vaziri-Sani, A. Delli, B. Lindblad, A. Carlsson, G. Forsander, BDD Study Group et coll.: triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes. Pediatr. Diabetes 14(2), 97–105 (2013)

    Article  CAS  Google Scholar 

  19. C. Shivaprasad, R. Mittal, M. Dharmalingam, P.K. Kumar, Zinc transporter-8 autoantibodies can replace IA-2 autoantibodies as a serological marker for juvenile onset type 1 diabetes in India. Indian J. Endocrinol. Metab. 18, 345–349 (2014)

    Article  CAS  Google Scholar 

  20. G.J. Kahaly, M.P. Hansen, Type 1 diabetes associated autoimmunity. Autoimmun. Rev. 15, 644–648 (2016)

    Article  CAS  Google Scholar 

  21. J.M. Barker, Clinical review: type 1 diabetes-associated autoimmunity: natural history, genetic associations, and screening. J. Clin. Endocrinol. Metab. 91, 1210–1217 (2006)

    Article  CAS  Google Scholar 

  22. A. Van den Driessche, V. Eenkhoorn, L. Van Gaal, C. De Block, Type 1 diabetes and autoimmune polyglandular syndrome: a clinical review. Neth. J. Med. 67(11), 376–387 (2009)

    PubMed  Google Scholar 

  23. B. Jonsdottir, C. Andersson, A. Carlsson, A. Delli, G. Forsander, J. Ludvigsson, C. Marcus, U. Samuelsson, E. Ortqvist, A. Lernmark, S.A. Ivarsson, H.E. Larsson, Better Diabetes Diagnosis (BDD) Study Group: thyroid autoimmunity in relation to islet autoantibodies and HLA-DQ genotype in newly diagnosed type 1 diabetes in children and adolescents. Diabetologia 56(8), 1735–1742 (2013)

    Article  CAS  Google Scholar 

  24. B. Jonsdottir, C. Larsson, M. Lundgren, A. Ramelius, I. Jönsson, H.E. Larsson, DiPiS study Group, Childhood thyroid autoimmunity and relation to islet autoan tibodies in children at risk for type 1 diabetes in the diabetes prediction in skåne (DiPiS) study. Autoimmunity 51(5), 228–237 (2018)

  25. A.D. Riquetto, R.M. de Noronha, E.M. Matsuo, E.J. Ishida, R.E. Vaidergorn, F. Soares et al. Thyroid function and autoimmunity in children and adolescents with type 1 diabetes mellitus. Diabetes Res. Clin. Pract. 110, e9–e11 (2015)

    Article  Google Scholar 

  26. A. Krzewska, I. Ben-Skowronek, Effect of associated autoimmune diseases on type 1 diabetes mellitus incidence and metabolic control in children and adolescents. Biomed. Res. Int. (2016), https://doi.org/10.1155/2016/6219730

  27. G.B. Hwang, J.S. Yoon, K.J. Park, H.S. Lee, J.S. Hwang, Prevalence of autoimmune thyroiditis in patients with type 1 diabetes: a long-term follow-up study. Ann. Pediatr. Endocrinol. Metab. 23(1), 33–37 (2018)

    Article  Google Scholar 

  28. K. Kakleas, E. Paschali, N. Kefalas et al. Factors for thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus. Ups. J. Med. Sci. 114(4), 214–220 (2009)

    Article  Google Scholar 

  29. O. Kordonouri, A. Klinghammer, E.B. Lang, A. Grüters-Kieslich, M. Grabert, R.W. Holl, and On behalf of the DPV-Initiative of the German Working Group for Pediatric Diabetology: thyroid autoimmunity in children and adolescents with type 1 diabetes: a multicenter survey. Diabetes Care 25(8), 1346–1350 (2002)

    Article  Google Scholar 

  30. A. Rogowicz-Frontczak, D. Zozulinska-Ziołkiewicz, M. Litwinowicz, P. Niedzwiecki, K. Wyka, B. Wierusz-Wysocka, Are zinc transporter type 8 antibodies a marker of autoimmune thyroiditis in non-obese adults with new-onset diabetes? Euro. J. Endocrinol. 170, 651–658 (2014)

    Article  CAS  Google Scholar 

  31. A. Akirov, O. Pinhas-Hamiel, Co-occurrence of type 1 diabetes mellitus and celiac disease. World J. Diabetes 6(5), 707–714 (2015)

    Article  Google Scholar 

  32. A. Szypowska, M. Błazik, L. Groele, E. Pańkowska, The prevalence of autoimmune thyroid disease and celiac disease in children and adolescents with type 1 diabetes mellitus. Pediatr. Endocrinol. Diabetes Metab. 14(4), 221–224 (2008)

    PubMed  Google Scholar 

  33. F. Vaziri-Sani, S. Oak, J. Radtke, K. Lernmark, K. Lynch, C.D. Agardh, C.M. Cilio, A.L. Lethagen, E. Ortqvist, M. Landin-Olsson, C. Törn, C.S. Hampe, ZnT8 autoantibody titers in type 1 diabetes patients decline rapidly after clinical onset. Autoimmunity 43(8), 598–606 (2010)

    Article  CAS  Google Scholar 

  34. J.M. Wenzlau, M. Walter, T.J. Gardner, L.M. Frisch, L. Yu, G.S. Eisenbarth, A.G. Ziegler, H.W. Davidson, J.C. Hutton, Kinetics of the post-onset decline in zinc transporter 8 autoantibodies in type 1 diabetic human subjects. J. Clin. Endocrinol. Metab. 95(10), 4712–4719 (2010)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank all of the study participants and the team of the Division of Diabetology, Department of Endocrinology, Medical University Sofia.

Funding

The study is fully funded by Medical University Sofia, Grant No. D-113/2018.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nevena Chakarova.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chakarova, N., Dimova, R., Serdarova, M. et al. Islet, thyroid and transglutaminase antibodies in adult Bulgarian patients with type 1 diabetes. Endocrine 70, 299–306 (2020). https://doi.org/10.1007/s12020-020-02395-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-020-02395-1

Keywords

Navigation