Type 1 Diabetes Onset in Children after COVID-19: Cross-Sectional Study

Background. The hypothesis on correlation between SARS-CoV-2 infection and diabetic ketoacidosis (DKA) development in patients with newly diagnosed type 1 diabetes (T1D) was proposed during the COVID-19 pandemic. The results of testing this hypothesis remain contradictory. Objective. Aim of the study — to analyse the correlation between COVID-19 and clinical characteristics of T1D onset in children. Methods. The study included data from the medical records of patients with newly diagnosed T1D and hospitalized from March 2020 to March 2021. The study group included patients with IgG to SARS-CoV-2 10 U/ml at hospital admission, control group — patients with no laboratory signs of COVID-19. Clinical forms of disease manifestation (hyperglycemia, ketosis, DKA) were recorded among T1D features, as well as DKA severity according to blood pH levels (mild — pH 7.3; moderate — pH = 7.1–7.2; severe — pH < 7.1). Results. The study group included data from 119 children, the control group — 320 with newly established T1D. Both groups were comparable in gender and age. T1D manifested with hyperglycemia in 35 (29.4%) patients, with ketosis — in 41 (34.5%), with DKA — in 43 (36.1%) in the study group; and in 81 (25.3%), 89 (27.8%) and 150 (46.9%) patients in the control group, respectively (p = 0.127). DKA was mild in 9 (20.9%), moderate in 24 (55.8%), and severe in 10 (23.3%) patients of study group; and in 36 (24%), 73 (48.7%) and 41 (27.3%) patients in the control group, respectively (p = 0.747). Conclusion: COVID-19 is not associated with the clinical form and severity of DKA at T1D onset.

1. Rabaan AA, Smajlović S, Tombuloglu H, et al. SARS-CoV-2 infection and multi-organ system damage: A review. Biomol Biomed. 2023;23(1):37–52. doi: https://doi.org/10.17305/bjbms.2022.7762

2. Parolin M, Parisotto M, Zanchetta F, et al. Coronaviruses and Endocrine System: A Systematic Review on Evidence and Shadows. Endocr Metab Immune Disord Drug Targets. 2021;21(7):1242–1251. doi: https://doi.org/10.2174/1871530320666200905123332

3. Memon B, Abdelalim EM. ACE2 function in the pancreatic islet: Implications for relationship between SARS-CoV-2 and diabetes. Acta Physiol (Oxf). 2021;233(4):e13733. doi: https://doi.org/10.1111/apha.13733

4. Wu CT, Lidsky PV, Xiao Y, et al. SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment. Cell Metab. 2021;33(8): 1565–1576.e5. doi: https://doi.org/10.1016/j.cmet.2021.05.013

5. Geravandi S, Mahmoudi-Aznaveh A, Azizi Z, et al. SARS-CoV-2 and pancreas: a potential pathological interaction? Trends Endocrinol Metab. 2021;32(11):842–845. doi: https://doi.org/10.1016/j.tem.2021.07.004

6. Ogarek N, Oboza P, Olszanecka-Glinianowicz M, Kocelak P. The endocrine system function disturbances during and after SARS-CoV-2 infection. Eur Rev Med Pharmacol Sci. 2022;26(6):2171–2178. doi: https://doi.org/10.26355/eurrev_202203_28365

7. Denina M, Trada M, Tinti D, et al. Increase in newly diagnosed type 1 diabetes and serological evidence of recent SARS-CoV-2 infection: Is there a connection? Front Med. 2022;9:927099. doi: https://doi.org/10.3389/fmed.2022.927099

8. Barrett CE, Koyama AK, Alvarez P, et al. Risk for Newly Diagnosed Diabetes >30 Days After SARS-CoV-2 Infection Among Persons Aged < 18 Years — United States, March 1, 2020-June 28, 2021. MMWR Morb Mortal Wkly Rep. 2022;71(2):59–65. doi: https://doi.org/10.15585/mmwr.mm7102e2

9. Rahmati M, Yon DK, Lee SW, et al. New-onset type 1 diabetes in children and adolescents as postacute sequelae of SARS-CoV-2 infection: A systematic review and meta-analysis of cohort studies. J Med Virol. 2023;95(6):e28833. doi: https://doi.org/10.1002/jmv.28833

10. Bombaci B, Passanisi S, Sorrenti L, et al. Examining the associations between COVID-19 infection and pediatric type 1 diabetes. Expert Rev Clin Immunol. 2023;19(5):489–497. doi: https://doi.org/10.1080/1744666X.2023.2189587

11. Boboc AA, Novac CN, Marin AG, et al. SARS-CoV-2 Positive Serology and Islet Autoantibodies in Newly Diagnosed Pediatric Cases of Type 1 Diabetes Mellitus: A Single-Center Cohort Study. Int J Mol Sci. 2023;24(10):8885. doi: https://doi.org/10.3390/ijms24108885

12. Salmi H, Heinonen S, Hästbacka J, et al. New-onset type 1 diabetes in Finnish children during the COVID-19 pandemic. Arch Dis Child. 2022;107(2):180–185. doi: https://doi.org/10.1136/archdischild-2020-321220

13. Delpeut J, Giani E, Louet D, et al. Variable incidence of ketoacidosis in youth with type 1 diabetes onset during COVID-19 pandemic peaks in France. Diabetes Metab. 2022;48(2):101322. doi: https://doi.org/10.1016/j.diabet.2022.101322

14. Rabbone I, Schiaffini R, Cherubini V, et al. Diabetes Study Group of the Italian Society for Pediatric Endocrinology and Diabetes. Has COVID-19 Delayed the Diagnosis and Worsened the Presentation of Type 1 Diabetes in Children? Diabetes Carе. 2020;43(11):2870–2872. doi: https://doi.org/10.2337/dc20-1321

15. Zubkiewicz-Kucharska A, Seifert M, Stępkowski M, et al. Diagnosis of type 1 diabetes during the SARS-CoV-2 pandemic: Does lockdown affect the incidence and clinical status of patients? Adv Clin Exp Med. 2021;30(2):127–134. doi: https://doi.org/10.17219/acem/130359

16. Lazareva AN, Rtishchev AYu, Vorontsova IG, et al. Social and medical aspects of the COVID-19 pandemic. Manifestation particularities of the newly diagnosed type 1 diabetes mellitus in children and adolescents during the COVID-19 pandemic. Pediatria. Journal n.a. G.N. Speransky. 2023;102(5):156–167. (In Russ). doi: https://doi.org/10.24110/0031-403X-2023-102-5-156-167

17. Ministry of Health of the Russian Federation. Profilaktika, diagnostika i lechenie novoi koronavirusnoi infektsii COVID-19: Temporary guidelines. Version 18 (26.10.2023). (In Russ).

18. Belyakova VV, Maiorova OA, Ivanova NV, et al. Assessment of serological tests for antibodies to different antigens of the SARS-CoV-2 virus: comparison of six immunoassays. Medical Immunology (Russia) = Meditsinskaya Immunologiya. 2021;23(6):1395–1404. (In Russ). doi: https://doi.org/10.15789/1563-0625-A0S-2228

19. Padoan A, Cosma C, Zaupa P, Plebani M. Analytical and diagnostic performances of a high-throughput immunoassay for SARS-CoV-2 IgM and IgG. medRxiv. 2020. doi: https://doi.org/10.1101/2020.11.20.20235267

20. Godkov MA, Shustov VV, Korshunov VA, et al. Formation of Herd Immunity to SARS-CoV-2 in the Population of Moscow. Epidemiology and Vaccinal Prevention. 2022;21(1):81–91. (In Russ). doi: https://doi.org/10.31631/2073-3046-2022-21-1-81-91

21. Sakharnyi diabet 1 tipa u detei: Clinical guidelines. Russian Association of Endocrinologists. Ministry of Health of Russian Federation; 2022. 62 p.

22. Suplotova LA, Smetanina SA, Makarova OB, et al. Dynamics of frequency of overweight and obesity children of young school age in the Tyumen region. Obesity and metabolism. 2019;16(1):34–38. (In Russ). doi: https://doi.org/10.14341/omet9692

23. Popova AYu, Andreeva EE, Babura EA, et al. Features of developing SARS-CoV-2 nucleocapsid protein population-based seroprevalence during the first wave of the COVID-19 epidemic in the Russian Federation. Russian Journal of Infection and Immunity = Infektsiya i immunitet. 2021;11(2):297–323. (In Russ). doi: https://doi.org/10.15789/2220-7619-FOD-1684

24. Samitova ER. Clinical and Epidemiological Features of COVID-19 in Children in Moscow in 2020-2022. Epidemiology and Vaccinal Prevention. 2022;21(5):38–48 (In Russ). doi: https://doi.org/10.31631/2073-3046-2022-21-5-38-48

25. Laptev DN, Bezlepkina OB, Sheshko EL, et al. Main epidemiological indicators of type 1 diabetes mellitus in children in the Russian Federation for 2014–2023. Problems of Endocrinology. 2024;70(5):76–83. (In Russ). doi: https://doi.org/10.14341/probl13515

26. Dedov II, Shestakova MV, Vikulova OK, et al. Epidemiological characteristics of diabetes mellitus in the Russian Federation: clinical and statistical analysis according to the Federal diabetes register data of 01.01.2021. Diabetes mellitus. 2021;24(3):204–221. (In Russ). doi: https://doi.org/10.14341/DM12759

27. Lemos JRN, Hirani K, von Herrath M. Immunological and virological triggers of type 1 diabetes: insights and implications. Front Immunol. 2024;14:1326711. doi: https://doi.org/10.3389/fimmu.2023.1326711

28. Regnell SE, Lernmark Å. Early prediction of autoimmune (type 1) diabetes. Diabetologia. 2017;60(8):1370–1381. doi: https://doi.org/10.1007/s00125-017-4308-1

29. Turin A, Drobnič Radobuljac M. Psychosocial factors affecting the etiology and management of type 1 diabetes mellitus: A narrative review. World J Diabetes. 2021;12(9):1518–1529. doi: https://doi.org/10.4239/wjd.v12.i9.1518

30. Kimpimäki T, Erkkola M, Korhonen S, et al. Short-term exclusive breastfeeding predisposes young children with increased genetic risk of Type I diabetes to progressive beta-cell autoimmunity. Diabetologia. 2001;44(1):63–69. doi: https://doi.org/10.1007/s001250051581

31. Lampousi AM, Carlsson S, Löfvenborg JE. Dietary factors and risk of islet autoimmunity and type 1 diabetes: a systematic review and meta-analysis. EBioMedicine. 2021;72:103633. doi: https://doi.org/10.1016/j.ebiom.2021.103633

32. Niinistö S, Cuthbertson D, Miettinen ME, et al. High Concentrations of Immunoglobulin G Against Cow Milk Proteins and Frequency of Cow Milk Consumption Are Associated With the Development of Islet Autoimmunity and Type 1 Diabetes-The Trial to Reduce Insulindependent Diabetes Mellitus (IDDM) in the Genetically at Risk (TRIGR) Study. J Nutr. 2024;154(8):2493–2500. doi: https://doi.org/10.1016/j.tjnut.2024.06.005

33. Esposito S, Toni G, Tascini G, et al. Environmental Factors Associated With Type 1 Diabetes. Front Endocrinol (Lausanne). 2019;10:592. doi: https://doi.org/10.3389/fendo.2019.00592

34. Durazzo M, Ferro A, Gruden G. Gastrointestinal Microbiota and Type 1 Diabetes Mellitus: The State of Art. J Clin Med. 2019;8(11):1843. doi: https://doi.org/10.3390/jcm8111843

35. Chia JSJ, McRae JL, Kukuljan S, et al. A1 beta-casein milk protein and other environmental pre-disposing factors for type 1 diabetes. Nutr Diabetes. 2017;7(5):e274. doi: https://doi.org/10.1038/nutd.2017.16

36. Kuitunen I, Artama M, Mäkelä L, et al. Effect of Social Distancing Due to the COVID-19 Pandemic on the Incidence of Viral Respiratory Tract Infections in Children in Finland During Early 2020. Pediatr Infect Dis J. 2020;39(12):e423–e427. doi: https://doi.org/10.1097/INF.0000000000002845

37. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi: https://doi.org/10.1016/S0140-6736(20)30183-5

38. Del Valle DM, Kim-Schulze S, Huang HH, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636–1643. doi: https://doi.org/10.1038/s41591-020-1051-9