Association of COVID-19 and Development of Type 1 Diabetes: A Danish Nationwide Register Study

Abstract

OBJECTIVE To compare the incidence of type 1 diabetes (T1D) before and during the coronavirus disease 2019 (COVID-19) pandemic and determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with T1D development. RESEARCH DESIGN AND METHODS All Danish residents age <30 years free of diabetes from 2015 to 2021 were included. Individuals were followed from 1 January 2015 or birth until the development of T1D, the age of 30, the end of the study (31 December 2021), emigration, development of type 2 diabetes, onset of any cancer, initiation of immunomodulating therapy, or development of any autoimmune disease. We compared the incidence rate ratio (IRR) of T1D using Poisson regression models. We matched each person with a SARS-CoV-2 infection with three control persons and used a cause-specific Cox regression model to estimate the hazard ratio (HR). RESULTS Among 2,381,348 individuals, 3,579 cases of T1D occurred. The adjusted IRRs for T1D in each quarter of 2020 and 2021 compared with 2015–2019 were as follows: January–March 2020, 1.03 (95% CI 0.86; 1.23); January–March 2021, 1.01 (0.84; 1.22), April–June 2020, 0.98 (0.80; 1.20); April–June 2021, 1.34 (1.12; 1.61); July–September 2020, 1.13 (0.94; 1.35); July–September 2021, 1.21 (1.01; 1.45); October–December 2020, 1.09 (0.91; 1.31); and October–December 2021, 1.18 (0.99; 1.41). We identified 338,670 individuals with a positive SARS-CoV-2 test result and matched them with 1,004,688 control individuals. A SARS-2-CoV infection was not significantly associated with the risk of T1D development (HR 0.90 [95% CI 0.60; 1.35]). CONCLUSIONS There was an increase in T1D incidence during April–June 2021 compared with April–June 2015–2019, but this could not be attributed to SARS-CoV-2 infection.

What does SARS‐CoV‐2 tell us about the aetiology of environmental triggers for diabetes in children and young people?

“…A registry study from Germany looking at 5127 children presenting with new‐onset diabetes in the COVID‐19 pandemic reported a similar association 2 . However, a nationwide study whilst reporting increases in new‐onset T1DM in the pandemic compared with previous years did not find this association 4 …”

“…Type 1 diabetes mellitus (T1DM) is caused by the autoimmune destruction of β cells in the pancreatic islets and accounts for over 90% of childhood diabetes. A significant increase in new‐onset childhood T1DM has been reported in the COVID‐19 pandemic, 1–4 but the link with SARS‐CoV‐2 remains an enigma. This quandary is not unique to SARS‐CoV‐2.…”

“…Geographical variation in rates of T1DM are well described, with both genetic and environmental factors proposed as the underlying reason for this variation. Aligned with this as a confounding factor in interpreting pandemic‐related data, several studies from different regions reported increases in new‐onset T1DM, 1–4 though one reported no significant increase 7 . Whilst reporting a 17% increase in incidence in the COVID pandemic year across UK and Ireland, geographical variation and clustering of new diabetes cases were evident; regionally, whilst some sites had significantly higher case frequency, others saw no change 1 …”

T‐cell immunity against Severe Acute Respiratory Syndrome Coronavirus 2 proteins in patients with type 1 diabetes

“…In the German study, the diagnosis of COVID‐19 in children was associated with an almost double increase in the incidence of T1D. In contrast, a Danish study found no significant association between SARS‐CoV‐2 infection and an increased risk of developing T1D 19–21 …”

“…In contrast, a Danish study found no significant association between SARS-CoV-2 infection and an increased risk of developing T1D. [19][20][21] Type 1 diabetes is an intricate autoimmune disease characterised by the destruction of insulin-producing cells by autoreactive immune cells. Environmental factors, such as viral infection, have the potential to initiate the destruction of insulin-producing beta cells.…”