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Type 1 diabetes mellitus following COVID-19 vaccination: a report of two cases and review of literature

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection, which led to the coronavirus 2019 (COVID-19) pandemic, has promoted the development of novel therapeutic agents and vaccines to combat the global spread of the virus. While the COVID-19 vaccines approved thus far have proven to be effective in clinical settings, there have been reports of autoimmune diseases occurring following vaccination, including autoimmune/inflammatory syndrome induced by adjuvant syndrome. We herein report two cases of type 1 diabetes mellitus that occurred following COVID-19 vaccination and provide a literature review. Both cases received multiple vaccinations as recommended to ensure optimal antibody titers. Moreover, the HLA associated with susceptibility to type 1 diabetes was prototypic in both cases. This indirect evidence suggests that the COVID-19 vaccines may be implicated in the pathogenesis of type 1 diabetes. Further case reports to establish a clearer understanding of a potential association are warranted.

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References

  1. Park JW, Lagniton PNP, Liu Y, Xu RH. mRNA vaccines for COVID-19: what, why and how. Int J Biol Sci. 2021;17:1446–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Pormohammad A, Zarei M, Ghorbani S, Mohammadi M, Razizadeh MH, et al. Efficacy and safety of COVID-19 vaccines: a systematic review and meta-analysis of randomized clinical trials. Vaccines (Basel). 2021;9:467.

    Article  CAS  PubMed  Google Scholar 

  3. Vera-Lastra O, Ordinola Navarro A, Cruz Domiguez MP, Medina G, Sánchez Valadez TI, et al. Two cases of Graves’ disease following SARS-CoV-2 vaccination: an autoimmune/inflammatory syndrome induced by adjuvants. Thyroid. 2021;31:1436–9.

    Article  CAS  PubMed  Google Scholar 

  4. An QJ, Qin DA, Pei JX. Reactive arthritis after COVID-19 vaccination. Hum Vaccin Immunother. 2021;17:2954–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Das L, Bhadada SK, Sood A. Post-COVID-vaccine autoimmune/inflammatory syndrome in response to adjuvants (ASIA syndrome) manifesting as subacute thyroiditis. J Endocrinol Invest. 2022;45:465–7.

    Article  CAS  PubMed  Google Scholar 

  6. Sharif N, Alzahrani KJ, Ahmed SN, Dey SK. Efficacy, immunogenicity and safety of COVID-19 vaccines: a systematic review and meta-analysis. Front Immunol. 2021;12: 714170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Tartof SY, Slezak JM, Fischer H, Hong V, Ackerson BK, et al. Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study. Lancet. 2021;398:1407–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Rosenberg ES, Dorabawila V, Easton D, et al. COVID-19 vaccine effectiveness by product and timing in New York State 2021. N Engl J Med. 2022;386:116–27.

    Article  CAS  PubMed  Google Scholar 

  9. Pomara C, Sessa F, Ciaccio M, Dieli F, Esposito M, et al. COVID-19 vaccine and death: causality algorithm according to the WHO Eligibility Diagnosis. Diagnostics (Basel). 2021;11:955.

    Article  CAS  PubMed  Google Scholar 

  10. Wang L, Wang FS, Gershwin ME, Gershwin E. Human autoimmune diseases: a comprehensive update. J Intern Med. 2015;278:369–95.

    Article  CAS  PubMed  Google Scholar 

  11. Pellegrino P, Carnovale C, Pozzi M, Antoniazzi S, Perrone V, Salvati D, et al. On the relationship between human papilloma virus vaccine and autoimmune diseases. Autoimmun Rev. 2014;13:736–41.

    Article  CAS  PubMed  Google Scholar 

  12. Segal Y, Shoenfeld Y. Vaccine-induced autoimmunity: the role of molecular mimicry and immune crossreaction. Cell Mol Immunol. 2018;15:586–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wraith DC, Goldman M, Lambert PH. Vaccination and autoimmune disease: what is the evidence? Lancet. 2003;15(362):1659–66.

    Article  Google Scholar 

  14. Ruggeri RM, Giovanellla L, Campennì A. SARS-CoV-2 vaccine may trigger thyroid autoimmunity: real-life experience and review of the literature. J Endocrinol Invest. 2022;45:2283–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rotondi M, Coperchini F, Ricci G, Denegri M, Croce L, Ngnitejeu ST, et al. Detection of SARS-COV-2 receptor ACE-2 mRNA in thyroid cells: a clue for COVID-19-related subacute thyroiditis. J Endocrinol Invest. 2021;44:1085–90.

    Article  CAS  PubMed  Google Scholar 

  16. Sakurai K, Narita D, Saito N, Ueno T, Sato R, et al. Type 1 diabetes mellitus following COVID-19 RNA-based vaccine. J Diabetes Investig. 2022;13:1290–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Erlich H, Valdes AM, Noble J, Carlson JA, Varney M, et al. HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families. Diabetes. 2008;57:1084–92.

    Article  CAS  PubMed  Google Scholar 

  18. Abdul-Rasoul M, Habib H, Al-Khouly M. ‘The honeymoon phase’ in children with type 1 diabetes mellitus: frequency, duration, and influential factors. Pediatr Diabetes. 2006;7:101–7.

    Article  PubMed  Google Scholar 

  19. Watad A, Sharif K, Shoenfeld Y. The ASIA syndrome: basic concepts. Mediterr J Rheumatol. 2017;28:64–9.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Xu S, Yang K, Li R, Zhang L. mRNA vaccine era-mechanisms, drug platform and clinical prospection. Int J Mol Sci. 2020;21:6582.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Teijaro JR, Farber DL. COVID-19 vaccines: modes of immune activation and future challenges. Nat Rev Immunol. 2021;21:195–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Li Z, Guo J, Bi L. Role of the NLRP3 inflammasome in autoimmune diseases. Biomed Pharmacother. 2020;130: 110542.

    Article  CAS  PubMed  Google Scholar 

  23. Samuel I, Hubert M. Innate viral sensor MDA5 and coxsackievirus interplay in type 1 diabetes development. Microorganisms. 2020;8:993.

    Article  Google Scholar 

  24. Sasaki K, Morioka T, Okada N, Natsuki Y, Kakutani Y, Ochi A, et al. New-onset fulminant type 1 diabetes after severe acute respiratory syndrome coronavirus 2 vaccination: a case report. J Diabetes Invest. 2022;13:1286–9.

    Article  CAS  Google Scholar 

  25. Yano M, Morioka T, Natsuki Y, Sasaki K, Kakutani Y, Ochi A, et al. New-onset type 1 diabetes after COVID-19 mRNA vaccination. Intern Med. 2022;61:1197–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sasaki H, Itoh A, Watanabe Y, Nakajima Y, Saisho Y, Irie J, et al. Newly developed type 1 diabetes after coronavirus disease 2019 vaccination: a case report. J Diabetes Invest. 2022;13:1105–8.

    Article  CAS  Google Scholar 

  27. Sato T, Kodama S, Kaneko K, Imai J, Katagiri H. Type 1 diabetes mellitus associated with nivolumab after second SARS-CoV-2 vaccination. Jpn Emerg Infect Dis. 2022;28:1518–20.

    Article  CAS  Google Scholar 

  28. Aydoğan Bİ, Ünlütürk U, Cesur M. Type 1 diabetes mellitus following SARS-CoV-2 mRNA vaccination. Endocrine. 2022;78:42–6.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Bleve E, Venditti V, Lenzi A, Morano S, Filardi T. COVID-19 vaccine and autoimmune diabetes in adults: report of two cases. J Endocrinol Invest. 2022;45:1269–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Patrizio A, Ferrari SM, Antonelli A, Fallahi P. A case of Graves’ disease and type 1 diabetes mellitus following SARS-CoV-2 vaccination. J Autoimmun. 2021;125: 102738.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Tang X, He B, Liu Z, Zhou Z, Li X. Fulminant type 1 diabetes after COVID-19 vaccination. Diabetes Metab. 2022;48: 101324.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ohuchi K, Amagai R, Tamabuchi E, Kambayashi Y, Fujimura T. Fulminant type 1 diabetes mellitus triggered by coronavirus disease 2019 vaccination in an advanced melanoma patient given adjuvant nivolumab therapy. J Dermatol. 2022;49:e167–8.

    Article  CAS  PubMed  Google Scholar 

  33. Moon H, Suh S, Park MK. Adult-onset type 1 diabetes development following COVID-19 mRNA vaccination. J Korean Med Sci. 2023;38: e12.

    Article  CAS  PubMed  Google Scholar 

  34. Tanaka S, Endo T, Aida K, Shimura H, Yokomori N, Kaneshige M, et al. Distinct diagnostic criteria of fulminant type 1 diabetes based on serum C-peptide response and HbA1c levels at onset. Diabetes Care. 2004;27:1936–41.

    Article  CAS  PubMed  Google Scholar 

  35. Burrack AL, Martinov T, Fife BT. T cell-mediated beta cell destruction: autoimmunity and alloimmunity in the context of type 1 diabetes. Front Endocrinol (Lausanne). 2017;8:343.

    Article  PubMed  Google Scholar 

  36. Nemoto M, Sugisawa H, Nishimura R, et al. Factors affecting the honeymoon period in adult-onset Japanese type 1 diabetes. J Jpn Diab Soc. 2011;54:98–102.

    CAS  Google Scholar 

  37. Chang L, Mo-Ning G, Zhonglin C, Zhong X, Guanjie C. Association between Covid-19 vaccination and incidence of type 1 diabetes in China: evidence from 14.14 million registered residents between 2007 and 2021. Diabetes Res Clin Pract. 2023;201:110723.

    Article  Google Scholar 

  38. Kawabata Y, Ikegami H, Awata T, Imagawa A, Maruyama T. Differential association of HLA with three subtypes of type 1 diabetes: fulminant, slowly progressive and acute-onset. Diabetologia. 2009;52:2513–21.

    Article  CAS  PubMed  Google Scholar 

  39. Imagawa A, Hanafusa T. Fulminant type 1 diabetes—east and west. J Clin Endocrinol Metab. 2023;108:e1473–8.

    Article  PubMed  Google Scholar 

  40. Tsutsumi C, Imagawa A, Ikegami H, Makino H, Kobayashi T. Class II HLA genotype in fulminant type 1 diabetes: a nationwide survey with reference to glutamic acid decarboxylase antibodies. J Diabetes Invest. 2012;3:62–9.

    Article  CAS  Google Scholar 

  41. Ikegami H, Ogihara T. Genetics of insulin-dependent diabetes mellitus. Endocr J. 1996;43:605–13.

    Article  CAS  PubMed  Google Scholar 

  42. Kawabata Y, Ikegami H. Genetics of fulminant type 1 diabetes. Diabetol Int. 2020;11:315–22.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

No special funding or grants were received for this study.

Author information

Authors and Affiliations

  1. Division of Diabetology and Metabolism, Department of Internal Medicine, Tokyo Women’s Medical University School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, Japan

    Shota Mochizuki, Junnosuke Miura, Kiwako Ucida, Ryo Kubota, Hirona Fujikawa, Satoshi Takagi, Naoshi Yoshida, Sachiko Ootake & Tetsuya Babazono

  2. Medical Corporation Sakakibara Koseikai Sakakibara Sapia Tower Clinic, 1-7-12, Marunouchi, Chiyoda-ku, Tokyo, Japan

    Sachiko Ootake

  3. Division of Hematology, Department of Internal Medicine, Tokyo Women’s Medical University School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, Japan

    Chika Fujimori, Akihito Shinohara & Junji Tanaka

Authors
  1. Shota Mochizuki
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  2. Junnosuke Miura
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  3. Kiwako Ucida
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Contributions

The manuscript was authored by SM; JM, ST, KU, RK, FH, ST, TH, NY, OS, FC, SA, TJ, and TB reviewed the manuscript and contributed to the discussion; JM is the guarantor of the report, has access to all data in the cases, and is responsible for the integrity of the data and the accuracy of data analysis.

Corresponding author

Correspondence to Junnosuke Miura.

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None of the authors have any potential conflicts of interest associated with this case report.

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Written consent was obtained from all patients to participate in this study.

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Supplementary Information

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13340_2024_695_MOESM1_ESM.pdf

Supplementary file1 Supplemental Figure 1 Insulin dose and HbA1c from the onset of type 1 diabetes to 21 months thereafter in Case 1. Course of insulin dosage after the onset of type 1 diabetes. Insulin levels gradually increased from 8 to 15 months after diabetes onset. Supplemental Figure 2 Insulin dose and HbA1c from the onset of type 1 diabetes to 16 months thereafter in Case 2. Insulin levels increased from 2 to 16 months after diabetes onset. Endogenous insulin secretory capacity is relatively preserved (PDF 109 KB)

Supplementary file2 (PDF 179 KB)

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Mochizuki, S., Miura, J., Ucida, K. et al. Type 1 diabetes mellitus following COVID-19 vaccination: a report of two cases and review of literature. Diabetol Int (2024). https://doi.org/10.1007/s13340-024-00695-9

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  • DOI: https://doi.org/10.1007/s13340-024-00695-9

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