BACKGROUND: An increased prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in children was observed in various diabetes centres worldwide during the COVID-19 pandemic. We aimed to evaluate trends in the prevalence of diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes before and during the COVID-19 pandemic, and to identify potential predictors of changes in diabetic ketoacidosis prevalence during the pandemic. METHODS: For this international multicentre study, we used data from 13 national diabetes registries (Australia, Austria, Czechia, Denmark, Germany, Italy, Luxembourg, New Zealand, Norway, Slovenia, Sweden, USA [Colorado], and Wales). The study population comprised 104 290 children and adolescents aged 6 months to younger than 18 years, who were diagnosed with type 1 diabetes between Jan 1, 2006, and Dec 31, 2021. The observed diabetic ketoacidosis prevalence in 2020 and 2021 was compared to predictions based on trends over the pre-pandemic years 2006-19. Associations between changes in diabetic ketoacidosis prevalence and the severity of the COVID-19 pandemic and containment measures were examined with excess all-cause mortality in the whole population and the Stringency Index from the Oxford COVID-19 Government Response Tracker. FINDINGS: 87 228 children and adolescents were diagnosed with type 1 diabetes between 2006 and 2019, 8209 were diagnosed in 2020, and 8853 were diagnosed in 2021. From 2006 to 2019, diabetic ketoacidosis at diagnosis of type 1 diabetes was present in 23 775 (27·3%) of 87 228 individuals and the mean annual increase in the prevalence of diabetic ketoacidosis in the total cohort from 2006 to 2019 was 1·6% (95% CI 1·3 to 1·9). The adjusted observed prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes was 39·4% (95% CI 34·0 to 45·6) in 2020 and 38·9% (33·6 to 45·0) in 2021, significantly higher than the predicted prevalence of 32·5% (27·8 to 37·9) for 2020 and 33·0% (28·3 to 38·5) for 2021 (p<0·0001 for both years). The prevalence of diabetic ketoacidosis was associated with the pandemic containment measures, with an estimated risk ratio of 1·037 (95% CI 1·024 to 1·051; p<0·0001) per ten-unit increase in the Stringency Index for 2020 and 1·028 (1·009 to 1·047; p=0·0033) for 2021, but was not significantly associated with excess all-cause mortality. INTERPRETATION: During the COVID-19 pandemic, there was a marked exacerbation of the pre-existing increase in diabetic ketoacidosis prevalence at diagnosis of type 1 diabetes in children. This finding highlights the need for early and timely diagnosis of type 1 diabetes in children and adolescents. FUNDING: German Federal Ministry for Education and Research, German Robert Koch Institute, German Diabetes Association, German Diabetes Foundation, Slovenian Research Agency, Welsh Government, Central Denmark Region, and Swedish Association of Local Authorities and Regions.

Barbara Davis Center for Diabetes University of Colorado School of Medicine Aurora CO USA

Centre of Epidemiology and Biostatistics Polytechnic University of Marche Ancona Italy

Children's Diabetes Centre Telethon Kids Institute The University of Western Australia Perth WA Australia

Denver Scool of Medicine Anschutz Medical Campus University of Colorado Aurora CO USA

Department of Endocrinology and Diabetes and Health Services Research Unit The Royal Children's Hospital Parkville Melbourne VIC Australia; Diabetes Research Murdoch Children's Research Institute Parkville Melbourne VIC Australia; Department of Paediatrics University of Melbourne Parkville Melbourne VIC Australia

Department of Paediatric Endocrinology and Diabetes Children's Hospital for Wales Cardiff UK

Department of Paediatrics County Hospital Ryhov Jönköping Sweden; Department of Clinical and Experimental Medicine Linköping University Linköping Sweden

Department of Paediatrics University of Otago Christchurch New Zealand

Department of Pediatric Diabetes and Endocrinology Centre Hospitalier Luxembourg Luxembourg

Department of Pediatric Endocrinology Diabetes and Metabolic Diseases UMC Ljubljana University Children's Hospital Ljubljana Slovenia; Faculty of Medicine University of Ljubljana Ljubljana Slovenia

Department of Pediatrics 2nd Faculty of Medicine Charles University Prague Prague Czechia; University Hospital Motol Prague Czechia

Department of Pediatrics and Adolescent Medicine and Steno Diabetes Center Aarhus Aarhus University Hospital Aarhus Denmark

Department of Pediatrics and Adolescent Medicine Kepler University Clinic Linz Austria

Department of Women's and Children's Health Salesi Hospital Ancona Italy

Diabetes Unit Bambino Gesù Childrens' Hospital Rome Italy

Division of Paediatric and Adolescent Medicine Oslo University Hospital Oslo Norway; Institute of Clinical Medicine University of Oslo Oslo Norway

Division of Pediatric Endocrinology and Diabetology Center of Child and Adolescent Medicine Justus Liebig University Giessen Germany

Division of Population Medicine School of Medicine Cardiff University Heath Park Cardiff UK

Institute of Epidemiology and Medical Biometry ZIBMT Ulm University Ulm Germany; German Center for Diabetes Research Munich Neuherberg Germany

NU Hospital Group Uddevalla Trollhättan Sweden; Institute of Clinical Sciences University of Gothenburg Gothenburg Sweden

Starship Children's Health and University of Auckland Auckland New Zealand

Steno Diabetes Center Copenhagen Copenhagen Denmark; Department of Clinical Medicine University of Copenhagen Copenhagen Denmark

Lancet Diabetes Endocrinol. 2022 Nov;10(11):763-765. doi: 10.1016/S2213-8587(22)00272-8. PubMed

Zobrazit více v PubMed

Wolfsdorf JI, Glaser N, Agus M, et al. ISPAD Clinical Practice Consensus Guidelines 2018: diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatr Diabetes. 2018;19(suppl 27):155–177. PubMed

White NH. Diabetic ketoacidosis in children. Endocrinol Metab Clin North Am. 2000;29:657–682. PubMed

Dhatariya KK, Glaser NS, Codner E, Umpierrez GE. Diabetic ketoacidosis. Nat Rev Dis Primers. 2020;6:40. PubMed

Aye T, Mazaika PK, Mauras N, et al. Impact of early diabetic ketoacidosis on the developing brain. Diabetes Care. 2019;42:443–449. PubMed PMC

Ghetti S, Kuppermann N, Rewers A, et al. Cognitive function following diabetic ketoacidosis in children with new-onset or previously diagnosed type 1 diabetes. Diabetes Care. 2020;43:2768–2775. PubMed PMC

Bui H, To T, Stein R, Fung K, Daneman D. Is diabetic ketoacidosis at disease onset a result of missed diagnosis? J Pediatr. 2010;156:472–477. PubMed

Wersäll JH, Adolfsson P, Forsander G, Ricksten SE, Hanas R. Delayed referral is common even when new-onset diabetes is suspected in children. A Swedish prospective observational study of diabetic ketoacidosis at onset of type 1 diabetes. Pediatr Diabetes. 2021;22:900–908. PubMed

Cherubini V, Grimsmann JM, Åkesson K, et al. Temporal trends in diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes between 2006 and 2016: results from 13 countries in three continents. Diabetologia. 2020;63:1530–1541. PubMed PMC

Hale T, Angrist N, Goldszmidt R, et al. A global panel database of pandemic policies (Oxford COVID-19 Government Response Tracker) Nat Hum Behav. 2021;5:529–538. PubMed

Lai PH, Lancet EA, Weiden MD, et al. Characteristics associated with out-of-hospital cardiac arrests and resuscitations during the novel coronavirus disease 2019 pandemic in New York City. JAMA Cardiol. 2020;5:1154–1163. PubMed PMC

Primessnig U, Pieske BM, Sherif M. Increased mortality and worse cardiac outcome of acute myocardial infarction during the early COVID-19 pandemic. ESC Heart Fail. 2021;8:333–343. PubMed PMC

Kamrath C, Mönkemöller 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;324:801–804. PubMed PMC

Ho J, Rosolowsky E, Pacaud D, et al. Diabetic ketoacidosis at type 1 diabetes diagnosis in children during the COVID-19 pandemic. Pediatr Diabetes. 2021;22:552–557. PubMed PMC

Lawrence C, Seckold R, Smart C, et al. Increased paediatric presentations of severe diabetic ketoacidosis in an Australian tertiary centre during the COVID-19 pandemic. Diabet Med. 2021;38 PubMed PMC

Goldman S, Pinhas-Hamiel O, Weinberg A, et al. Alarming increase in ketoacidosis in children and adolescents with newly diagnosed type 1 diabetes during the first wave of the COVID-19 pandemic in Israel. Pediatr Diabetes. 2022;23:10–18. PubMed

Nagl K, Waldhör T, Hofer SE, et al. Alarming increase of ketoacidosis prevalence at type 1 diabetes-onset in Austria—results from a nationwide registry. Front Pediatr. 2022;10 PubMed PMC

Alfayez OM, Aldmasi KS, Alruwais NH, et al. Incidence of diabetic ketoacidosis among pediatrics with type 1 diabetes prior to and during COVID-19 pandemic: a meta-analysis of observational studies. Front Endocrinol. 2022;13 PubMed PMC

Karlinsky A, Kobak D. Tracking excess mortality across countries during the COVID-19 pandemic with the World Mortality Dataset. eLife. 2021;10:10. PubMed PMC

von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370:1453–1457. PubMed

Kamrath C, Rosenbauer J, Eckert AJ, et al. Incidence of type 1 diabetes in children and adolescents during the COVID-19 pandemic in Germany: results from the DPV Registry. Diabetes Care. 2022;45:1762–1771. PubMed

Gottesman BL, Yu J, Tanaka C, Longhurst CA, Kim JJ. Incidence of new-onset type 1 diabetes among US children during the COVID-19 global pandemic. JAMA Pediatr. 2022;176:414–415. PubMed PMC

Kamrath C, Rosenbauer J, Eckert AJ, et al. Glycated hemoglobin at diagnosis of type 1 diabetes and at follow-up in children and adolescents during the COVID-19 pandemic in Germany. Pediatr Diabetes. 2022;23:749–753. PubMed PMC

Kamrath C, Rosenbauer J, Tittel SR, et al. Frequency of autoantibody-negative type 1 diabetes in children, adolescents, and young adults during the first wave of the COVID-19 pandemic in Germany. Diabetes Care. 2021;44:1540–1546. PubMed

Chiarelli F, Rewers M, Phillip M. Screening of islet autoantibodies for children in the general population: a Position Statement endorsed by the European Society for Pediatric Endocrinology. Horm Res Paediatr. 2022 doi: 10.1159/000525824. published online July 1. PubMed DOI

Ghalwash M, Dunne JL, Lundgren M, et al. Two-age islet-autoantibody screening for childhood type 1 diabetes: a prospective cohort study. Lancet Diabetes Endocrinol. 2022;10:589–596. PubMed PMC

Wolf RM, Noor N, Izquierdo R, et al. Increase in newly diagnosed type 1 diabetes in youth during the COVID-19 pandemic in the United States: a multi-center analysis. Pediatr Diabetes. 2022;23:433–438. PubMed PMC

Association of Diabetic Ketoacidosis at Onset, Diabetes Technology Uptake, and Clinical Outcomes After 1 and 2 Years of Follow-up: A Collaborative Analysis of Pediatric Registries Involving 9,269 Children With Type 1 Diabetes From Nine Countries