Abstract
Objective
Acute worsening of glycemic control in diabetic patients and new–onset type I diabetes were reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Latent autoimmune diabetes in adults (LADA) is defined as a slowly evolving immune–mediated diabetes. A few cases of LADA diagnosed after SARS-CoV-2 vaccination have been reported in the literature. This study aims to report LADA after mRNA-based SARS-CoV-2 vaccinations in subjects with a history of well-controlled type 2 diabetes.
Methods
We report four cases with LADA diagnosed after mRNA-based SARS-CoV-2 vaccine, BNT162b2 (Pfizer-BioNTech). In the medical history, all subjects had well-controlled type 2 diabetes with oral anti-diabetic medication. One case had autoimmune thyroid disease. One subject was presented with diabetic ketoacidosis.
Results
Glycemic control of the presented cases had deteriorated 6–10 weeks after BNT162b2 vaccination. All patients were male and had high levels of glutamic acid decarboxylase 65 antibody (GAD65ab). An intensive insulin regimen was initiated at the time of diagnosis. The need for insulin therapy in two patients disappeared during follow-up. Two subjects were managed with basal insulin and oral antidiabetics. GAD65ab disappeared just 1 year after the diagnosis of LADA in a subject.
Conclusion
In case of impaired glycemic control after SARS-CoV-2 vaccination in a well-controlled diabetic patient, LADA should be considered.
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References
Chi Q, Yang Z, Xu K, Wang C, Liang H. DNA Nanostructure as an efficient drug delivery platform for immunotherapy. Front Pharmacol. 2019;10:1585.
Singh AK, Gupta R, Ghosh A, Misra A. Diabetes in COVID-19: prevalence, pathophysiology, prognosis and practical considerations. Diabetes Metab Syndr. 2020;14(4):303–10.
Shang J, Wang Q, Zhang H, et al. The relationship between diabetes mellitus and COVID-19 prognosis: a retrospective cohort study in Wuhan. China Am J Med. 2021;134(1):e6–14.
Cariou B, Wargny M, Boureau AS, et al. Impact of diabetes on COVID-19 prognosis beyond comorbidity burden: the CORONADO initiative. Diabetologia. 2022;65(9):1436–49.
Zhu L, She ZG, Cheng X, et al. Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes. Cell Metab. 2020;31(6):1068-1077 e1063.
Holman N, Knighton P, Kar P, et al. Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study. Lancet Diabetes Endocrinol. 2020;8(10):823–33.
Barron E, Bakhai C, Kar P, et al. Associations of type 1 and type 2 diabetes with COVID-19-related mortality in England: a whole-population study. Lancet Diabetes Endocrinol. 2020;8(10):813–22.
American Diabetes Association Professional Practice C. 4. Comprehensive medical evaluation and assessment of comorbidities: standards of medical care in diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S46–59.
Sendur SN, Oguz SH, Unluturk U. COVID-19 vaccination and thyroiditis. Best Pract Res Clin Endocrinol Metab. 2023;37(4):101759
Bahcecioglu AB, Karahan ZC, Aydogan BI, Kalkan IA, Azap A, Erdogan MF. Subacute thyroiditis during the COVID-19 pandemic: a prospective study. J Endocrinol Invest. 2022;45(4):865–74.
Yano M, Morioka T, Natsuki Y, et al. New-onset type 1 diabetes after COVID-19 mRNA vaccination. Intern Med. 2022;61(8):1197–200.
Aydogan BI, Unluturk U, Cesur M. Type 1 diabetes mellitus following SARS-CoV-2 mRNA vaccination. Endocrine. 2022;78(1):42–6.
Samuel SM, Varghese E, Triggle CR, Busselberg D. COVID-19 vaccines and hyperglycemia-is there a need for postvaccination surveillance? Vaccines (Basel). 2022;10(3):454.
Sasaki K, Morioka T, Okada N, et al. New-onset fulminant type 1 diabetes after severe acute respiratory syndrome coronavirus 2 vaccination: a case report. J Diabetes Investig. 2022;13(7):1286–9.
Sakurai K, Narita D, Saito N, et al. Type 1 diabetes mellitus following COVID-19 RNA-based vaccine. J Diabetes Investig. 2022;13(7):1290–2.
Tang X, He B, Liu Z, Zhou Z, Li X. Fulminant type 1 diabetes after COVID-19 vaccination. Diabetes Metab. 2022;48(2): 101324.
Kobayashi T, Yakou F, Saburi M, et al. New-onset atypical fulminant type 1 diabetes after COVID-19 vaccination: a case report. Clin Case Rep. 2022;10(10): e6473.
Lin R, Lin YW, Chen MH. Fulminant type 1 diabetes mellitus after SARS-CoV-2 vaccination: a case report. Vaccines (Basel). 2022;10(11):1905.
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(6):1269–70.
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.
Sasaki H, Itoh A, Watanabe Y, et al. Newly developed type 1 diabetes after coronavirus disease 2019 vaccination: a case report. J Diabetes Investig. 2022;13(6):1105–8.
Bally K, Ji B, Soni L. COVID-19 vaccine-induced latent autoimmune diabetes in adults. Cureus. 2023;15(1): e33762.
Grani G, Lamartina L, Durante C, Filetti S, Cooper DS. Follicular thyroid cancer and Hurthle cell carcinoma: challenges in diagnosis, treatment, and clinical management. Lancet Diabetes Endocrinol. 2018;6(6):500–14.
Ben Nasr M, D’Addio F, Montefusco L, et al. Indirect and direct effects of SARS-CoV-2 on human pancreatic islets. Diabetes. 2022;71(7):1579–90.
Vojdani A, Kharrazian D. Potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases. Clin Immunol. 2020;217: 108480.
Kanzy A, Madkhali M, Imam S, Jaume J. IDF21-0512 development of latent autoimmune diabetes of adults post SARS-COV-2 mRNA vaccination. Diabetes Res Clin Prac. 2022;186: 109369.
Schinas G, Polyzou E, Dimakopoulou V, Tsoupra S, Gogos C, Akinosoglou K. Immune-mediated liver injury following COVID-19 vaccination. World J Virol. 2023;12(2):100–8.
Sgamato C, Rocco A, Compare D, et al. Autoimmune liver diseases and SARS-CoV-2. World J Gastroenterol. 2023;29(12):1838–51.
Akkuzu G, Bes C, Ozgur DS, et al. Inflammatory rheumatic diseases developed after COVID-19 vaccination: presentation of a case series and review of the literature. Eur Rev Med Pharmacol Sci. 2023;27(5):2143–51.
Alqatari S, Ismail M, Hasan M, et al. Emergence of post COVID-19 vaccine autoimmune diseases: a single center study. Infect Drug Resist. 2023;16:1263–78.
Chourasia P, Goyal L, Kansal D, et al. Risk of new-onset diabetes mellitus as a post-COVID-19 condition and possible mechanisms: a scoping review. J Clin Med. 2023;12(3):1159.
Unsworth R, Wallace S, Oliver NS, et al. New-onset type 1 diabetes in children during COVID-19: multicenter regional findings in the U.K. Diabetes Care. 2020;43(11):e170–1.
Kamrath C, Monkemoller K, Biester T, et al. Ketoacidosis in children and adolescents with newly diagnosed type 1 diabetes during the COVID-19 pandemic in Germany. JAMA. 2020;324(8):801–4.
Sathish T, Cao Y, Kapoor N. Newly diagnosed diabetes in COVID-19 patients. Prim Care Diabetes. 2021;15(1):194.
Kuchay MS, Reddy PK, Gagneja S, Mathew A, Mishra SK. Short term follow-up of patients presenting with acute onset diabetes and diabetic ketoacidosis during an episode of COVID-19. Diabetes Metab Syndr. 2020;14(6):2039–41.
Vojdani A, Vojdani E, Kharrazian D. Reaction of human monoclonal antibodies to SARS-CoV-2 proteins with tissue antigens: implications for autoimmune diseases. Front Immunol. 2020;11: 617089.
Wu CT, Lidsky PV, Xiao Y, et al. SARS-CoV-2 infects human pancreatic beta cells and elicits beta cell impairment. Cell Metab. 2021;33(8):1565-1576 e1565.
Coate KC, Cha J, Shrestha S, et al. SARS-CoV-2 cell entry factors ACE2 and TMPRSS2 are expressed in the microvasculature and ducts of human pancreas but are not enriched in beta cells. Cell Metab. 2020;32(6):1028-1040 e1024.
Muller JA, Gross R, Conzelmann C, et al. SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas. Nat Metab. 2021;3(2):149–65.
Shoenfeld Y, Agmon-Levin N. ‘ASIA’ - autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. 2011;36(1):4–8.
Bragazzi NL, Hejly A, Watad A, Adawi M, Amital H, Shoenfeld Y. ASIA syndrome and endocrine autoimmune disorders. Best Pract Res Clin Endocrinol Metab. 2020;34(1): 101412.
Xu S, Yang K, Li R, Zhang L. mRNA vaccine era-mechanisms, drug platform and clinical prospection. Int J Mol Sci. 2020;21(18):6582.
Kanduc D, Shoenfeld Y. Molecular mimicry between SARS-CoV-2 spike glycoprotein and mammalian proteomes: implications for the vaccine. Immunol Res. 2020;68(5):310–3.
Cousminer DL, Ahlqvist E, Mishra R, et al. First genome-wide association study of latent autoimmune diabetes in adults reveals novel insights linking immune and metabolic diabetes. Diabetes Care. 2018;41(11):2396–403.
Buzzetti R, Tuomi T, Mauricio D, et al. Management of latent autoimmune diabetes in adults: a consensus statement from an international expert panel. Diabetes. 2020;69(10):2037–47.
ElSayed NA, Aleppo G, Aroda VR, et al. 2. Classification and diagnosis of diabetes: standards of care in diabetes-2023. Diabetes Care. 2023;46(Suppl 1):S19–40.
Brophy S, Davies H, Mannan S, Brunt H, Williams R. Interventions for latent autoimmune diabetes (LADA) in adults. Cochrane Database Syst Rev. 2011;(9):CD006165. https://doi.org/10.1002/14651858.CD006165.pub3.
Zampetti S, Campagna G, Tiberti C, et al. High GADA titer increases the risk of insulin requirement in LADA patients: a 7-year follow-up (NIRAD study 7). Eur J Endocrinol. 2014;171(6):697–704.
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The study was approved by Local Ethical Committee of Ankara Güven Hospital. Informed consent was obtained from all patients.
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Aydoğan, B.İ., Ünlütürk, U. & Cesur, M. Diagnosis of latent autoimmune diabetes after SARS–Cov2 vaccination in adult patients previously diagnosed with type 2 diabetes mellitus. Int J Diabetes Dev Ctries (2023). https://doi.org/10.1007/s13410-023-01261-w
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DOI: https://doi.org/10.1007/s13410-023-01261-w