Sascha René Tittel1,2, Joachim Rosenbauer2,3, Clemens Kamrath4, Julian Ziegler5, Felix Reschke6, Johanna Hammersen7, Kirsten Mönkemöller8, Angeliki Pappa9, Thomas Kapellen10, Reinhard Walter Holl. 1. Institute for Epidemiology and Medical Biometry, ZIBMT, Ulm University, Ulm, Germany sascha.tittel@uni-ulm.de. 2. German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany. 3. Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 4. Division of Paediatric Endocrinology and Diabetology, Centre of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany. 5. University Children's Hospital Tübingen, Tübingen, Germany. 6. Diabetes Centre for Children and Adolescents, Kinder- und Jugendkrankenhaus Auf der Bult, Hannover, Germany. 7. Department of Paediatrics, University Hospital Erlangen, Erlangen, Germany. 8. Department of Paediatrics, Kinderkrankhenhaus Amsterdamer Straße, Cologne, Germany. 9. Department of Paediatrics and Adolescent Medicine, University Hospital RWTH Aachen, Aachen, Germany. 10. Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
Psychological stress is a known general health risk potentially increasing the risk of type 1 diabetes. Consistent with this hypothesis, there were reports of a higher incidence of type 1 diabetes after other stressful catastrophic events, e.g., the Chernobyl incident in 1986 or the Los Angeles earthquake in 1994 (1,2). Over the past few months, coronavirus disease 2019 (COVID-19) and subsequent social distancing have affected biological, psychological, economic, and social aspects of life. Social distancing during the lockdown could be perceived as a stressful situation for children and adolescents, who could not attend kindergarten or school and were unable to pursue hobbies like sports or meeting friends. Perceived stress caused by feelings of isolation may have increased the risk of type 1 diabetes (3). Since type 1 diabetes is also associated with viral infections (4), explaining, for example, the higher type 1 diabetes incidence during winter months, COVID-19infection may have caused an increase of type 1 diabetes manifestations by affecting immune regulation or by directly damaging pancreatic β-cells (5). On the contrary, during the lockdown period between March and May 2020 in Germany, the incidence of type 1 diabetes could also have decreased, since people were less exposed to common infections.We aimed to assess a possible change in pediatric type 1 diabetes incidence during the COVID-19 lockdown.Out of 217 German pediatric diabetes centers participating in the Diabetes-Prospective Follow-up registry (DPV), 216 centers provided us with information about incident type 1 diabetes cases. We included pediatric type 1 diabetespatients with onset age between 6 months and <18 years diagnosed between 13 March and 13 May in each year between 2011 and 2020, corresponding to the lockdown period in Germany in 2020. For each year, we related the number of cases to the respective patient-years at risk—obtained from the Federal Statistical Office—to estimate the incidence per 100,000 patient-years with 95% CI. Applying Poisson regression, we predicted the type 1 diabetes incidence for 2020 based on data from 2011–2019 and compared these with the observed incidence. Additionally, we stratified the analyses by sex and age-group (<6, 6 to <12, 12 to <18 years).Overall, the type 1 diabetes incidence increased from 16.4 [95% CI 14.7–18.2] in 2011 to 22.2 [20.3–24.2] in 2019 (P = 0.04). The incidence in 2020, based on 532 cases among 13.6 million subjects <18 years, was 23.4 [21.5–25.5] and did not differ significantly from the prediction (22.1 [20.4–23.9]) (Fig. 1). Stratifying by age-group or sex, we also found no significant differences between observed and estimated incidence in 2020. However, we observed a nonsignificantly higher incidence in males in 2020 (28.1 [25.1–31.3]) compared with the predicted incidence of 23.1 [20.8–25.7]. In females, the observed incidence in 2020 was lower than the predicted incidence (18.6 [16.2–21.4] vs. 20.9 [18.6–23.5]).
Figure 1
Type 1 diabetes incidence of patients <18 years during the period 13 March to 13 May (corresponding to the German lockdown period in 2020) in the years 2011 to 2020.
Type 1 diabetes incidence of patients <18 years during the period 13 March to 13 May (corresponding to the German lockdown period in 2020) in the years 2011 to 2020.The type 1 diabetes incidence in 2020 follows the increasing trend observed between 2011 and 2019 without up- or downward deviation, indicating no short-term influence of the COVID-19 pandemic. Thus, strong direct diabetogenic effects seem very unlikely, but weak effects cannot be excluded given the relatively low COVID-19infection rate in Germany. It remains unclear whether elevated stress levels and reduced infection rates outweigh each other regarding effects on the onset of type 1 diabetes in children and adolescents or whether they have no measurable impact on incidence. However, there may be a delay between immunologic factors or infections and the onset of type 1 diabetes. It is therefore crucial to conduct long-term follow-up studies to investigate possible associations between the COVID-19 pandemic and the incidence of type 1 diabetes.
Authors: Janis A Müller; Rüdiger Groß; Carina Conzelmann; Jana Krüger; Uta Merle; Johannes Steinhart; Tatjana Weil; Lennart Koepke; Caterina Prelli Bozzo; Clarissa Read; Giorgio Fois; Tim Eiseler; Julia Gehrmann; Joanne van Vuuren; Isabel M Wessbecher; Manfred Frick; Ivan G Costa; Markus Breunig; Beate Grüner; Lynn Peters; Michael Schuster; Stefan Liebau; Thomas Seufferlein; Steffen Stenger; Albrecht Stenzinger; Patrick E MacDonald; Frank Kirchhoff; Konstantin M J Sparrer; Paul Walther; Heiko Lickert; Thomas F E Barth; Martin Wagner; Jan Münch; Sandra Heller; Alexander Kleger Journal: Nat Metab Date: 2021-02-03
Figure 1