Ketoacidosis in Children and Adolescents With Newly Diagnosed Type 1 Diabetes During the COVID-19 Pandemic in Germany | Acid Base, Electrolytes, Fluids | JAMA | JAMA Network
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Table 1.  Characteristics of Pediatric Patients Newly Diagnosed With Type 1 Diabetes in Germany From March 13 Through May 13, 2020, During the COVID-19 Pandemic, and During the Same Period in 2019 and 2018
Characteristics of Pediatric Patients Newly Diagnosed With Type 1 Diabetes in Germany From March 13 Through May 13, 2020, During the COVID-19 Pandemic, and During the Same Period in 2019 and 2018
Table 2.  Adjusted Relative Risk of Diabetic Ketoacidosis and Severe Diabetic Ketoacidosis at Diabetes Diagnosis From March 13 Through May 13, 2020, During the COVID-19 Pandemic, Compared With the Same Periods in 2019 and 2018
Adjusted Relative Risk of Diabetic Ketoacidosis and Severe Diabetic Ketoacidosis at Diabetes Diagnosis From March 13 Through May 13, 2020, During the COVID-19 Pandemic, Compared With the Same Periods in 2019 and 2018
1.
Baum  A, Schwartz  MD.  Admissions to Veterans Affairs hospitals for emergency conditions during the COVID-19 pandemic.   JAMA. 2020;324(1):96-99. doi:10.1001/jama.2020.9972PubMedGoogle ScholarCrossref
2.
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(8):1530-1541. doi:10.1007/s00125-020-05152-1PubMedGoogle ScholarCrossref
3.
Karges  B, Schwandt  A, Heidtmann  B,  et al.  Association of insulin pump therapy vs insulin injection therapy with severe hypoglycemia, ketoacidosis, and glycemic control among children, adolescents, and young adults with type 1 diabetes.   JAMA. 2017;318(14):1358-1366. doi:10.1001/jama.2017.13994PubMedGoogle ScholarCrossref
4.
Lazzerini  M, Barbi  E, Apicella  A, Marchetti  F, Cardinale  F, Trobia  G.  Delayed access or provision of care in Italy resulting from fear of COVID-19.   Lancet Child Adolesc Health. 2020;4(5):e10-e11. doi:10.1016/S2352-4642(20)30108-5PubMedGoogle ScholarCrossref
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    Severe Ketoacidosis During The COVID-19 pandemic
    Devi Dayal, MD | Endocrinology and Diabetes Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India.
    The article confirms the fears about an increase in severity of diabetic ketoacidosis (DKA) in children and adolescents with onset of type 1 diabetes (T1D) during the COVID-19 pandemic. The data hint at delays in access to healthcare even in a developed country like Germany. Parents’ fear of approaching healthcare services appears to be one of the major factors responsible for delayed presentations to a health facility, especially in those with severe DKA.

    The situation in the developing countries is even worse, where almost all children with onset of T1D are presenting to the hospitals in severe DKA
    (1,2). Although parental fear of exposure to COVID-19 in hospital settings and their ignorance of initial symptoms of diabetes plays some role, the main reason for severe DKA presentations is a virtual closure of medical services due to crumbled healthcare infrastructure in low-resource setups (2). I therefore strongly agree with the authors that education of public and healthcare workers is urgently needed to reduce presentations in DKA as well as severity of DKA, by emphasizing to parents they should bring sick children to hospitals without delay. β-cell antibody screening as suggested by the authors as another option is impractical during an ongoing pandemic (3).

    References

    1. Dayal D, Gupta S, Raithatha D, Jayashree M. Missing during COVID-19 lockdown: Children with onset of type 1 diabetes [published online ahead of print, 2020 Jun 23]. Acta Paediatr. 2020;10.1111/apa.15443. doi:10.1111/apa.15443

    2. Dayal D, Gupta S, Raithatha D, Soni P, Kumar S, Baranwal A. Near-fatal experience due to delayed diagnosis of type 1 diabetes during the COVID-19 pandemic. April 28, 2020, Preprint (Version 1). Available at Research Square https://doi.org/:10.21203/rs.3.rs-25337/v1.

    3. Ziegler AG, Kick K, Bonifacio E, et al. Yield of a Public Health Screening of Children for Islet Autoantibodies in Bavaria, Germany. JAMA. 2020;323(4):339-351. doi:10.1001/jama.2019.21565
    CONFLICT OF INTEREST: None Reported
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    Research Letter
    July 20, 2020

    Ketoacidosis in Children and Adolescents With Newly Diagnosed Type 1 Diabetes During the COVID-19 Pandemic in Germany

    Author Affiliations
    • 1Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany
    • 2Department of Pediatrics, Kinderkrankenhaus Amsterdamer Strasse, Cologne, Germany
    • 3Diabetes Center for Children and Adolescents, Children’s Hospital Auf der Bult, Hannover, Germany
    • 4Department of Pediatrics, Saarland University Medical Center, Homburg/Saar, Germany
    • 5Department of Pediatrics, Technical University of Munich School of Medicine, Munich, Germany
    • 6Department of Pediatrics, University Hospital Erlangen, Erlangen, Germany
    • 7Institute of Epidemiology and Medical Biometry (ZIBMT), Ulm University, Ulm, Germany
    JAMA. 2020;324(8):801-804. doi:10.1001/jama.2020.13445

    During the coronavirus disease 2019 (COVID-19) pandemic, a significantly lower rate of health care use has been reported, potentially leading to delayed medical care.1 Diabetic ketoacidosis is an acute life-threatening complication of a delayed diagnosis of type 1 diabetes.2 We investigated the frequency of diabetic ketoacidosis in children and adolescents at diagnosis of type 1 diabetes in Germany during the first 2 months of the COVID-19 pandemic.

    Methods

    This study used data from the German Diabetes Prospective Follow-up Registry (DPV) of children and adolescents with the diagnosis of type 1 diabetes between March 13, 2020, when most kindergartens and schools were closed to reduce interpersonal contacts, through May 13, 2020. The DPV registry has a nationwide coverage of more than 90% of pediatric patients with type 1 diabetes.3 Since 2018, 217 diabetes centers (hospitals and medical practices) have transferred information from pediatric patients with newly diagnosed type 1 diabetes.

    Diabetic ketoacidosis was defined as a pH level less than 7.3 and/or bicarbonate level less than 15 mmol/L, and severe diabetic ketoacidosis as a pH level less than 7.1 and/or bicarbonate level less than 5 mmol/L.2,3 The frequencies of diabetic ketoacidosis and severe diabetic ketoacidosis observed during the COVID-19 period were compared with the same periods in 2018 and 2019 using multivariable logistic regression, adjusting for age, sex, and immigrant background (defined as patient or at least 1 parent born outside Germany). Differences were presented as adjusted relative risks (aRRs) with 95% CIs. A 2-sided P < .05 was considered statistically significant. All analyses were performed with SAS version 9.4 (SAS Institute Inc). Informed consent for participation in the DPV registry was obtained from patients or their parents by verbal or written procedure, as approved by the responsible data protection officers at each center. The analysis of anonymized data was approved by the ethics committee of the University of Ulm.

    Results

    We obtained and analyzed data of 532 children and adolescents with newly diagnosed type 1 diabetes from March 13 through May 13, 2020, from 216 of 217 diabetes centers. The median age of the cohort was 9.9 years (interquartile range, 5.8-12.9 years; 61.5% male) (Table 1). Diabetic ketoacidosis was present in 238 patients (44.7%) and severe ketoacidosis in 103 patients (19.4%) (Table 1). During the COVID-19 period in 2020, the frequency of diabetic ketoacidosis was significantly higher compared with the 2 previous years (44.7% in 2020 vs 24.5% in 2019; aRR, 1.84 [95% CI, 1.54-2.21]; P < .001; vs 24.1% in 2018; aRR, 1.85 [95% CI, 1.54-2.24]; P < .001). The incidence of severe diabetic ketoacidosis was also significantly higher compared with the previous years (19.4% in 2020 vs 13.9% in 2019; aRR, 1.37 [95% CI, 1.04-1.81]; P = .03; vs 12.3% in 2018; aRR, 1.55 [95% CI, 1.15-2.10]; P = .004) (Table 2). Children younger than 6 years had the highest risk for diabetic ketoacidosis (51.9% in 2020 vs 18.4% in 2019; aRR, 2.75 [95% CI, 1.88-4.02]; P < .001; vs 24.2% in 2018; aRR, 2.12 [95% CI, 1.48-3.02]; P < .001) and severe diabetic ketoacidosis (24.4% in 2020 vs 12.2% in 2019; aRR, 1.90 [95% CI, 1.12-3.23]; P = .02; vs 11.7% in 2018; aRR, 2.06 [95% CI, 1.16-3.65]; P = .01) during the COVID-19 pandemic (Table 2).

    Discussion

    This study found a significant increase in diabetic ketoacidosis and severe ketoacidosis at diabetes diagnosis in children and adolescents during the COVID-19 pandemic in Germany. Underlying causes may be multifactorial and reflect reduced medical services, fear of approaching the health care system, and more complex psychosocial factors.1,4

    Limitations of this study include that the individual socioeconomic status and a family history of diabetes were not available.

    Further research into the possible causes of the increase in diabetic ketoacidosis during the COVID-19 pandemic and interventions to reduce diabetic ketoacidosis, such as public and health care clinician education or β-cell antibody screening, is required.

    Section Editor: Jody W. Zylke, MD, Deputy Editor.
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    Article Information

    Corresponding Author: Clemens Kamrath, MD, Center of Child and Adolescent Medicine, Justus Liebig University, Feulgenstr 12, 35385 Giessen, Germany (clemens.kamrath@paediat.med.uni-giessen.de).

    Accepted for Publication: July 8, 2020.

    Published Online: July 20, 2020. doi:10.1001/jama.2020.13445

    Author Contributions: Dr Holl had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Kamrath and Mönkemöller contributed equally to this work.

    Concept and design: Kamrath, Mönkemöller, Holl.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: Kamrath, Holl.

    Critical revision of the manuscript for important intellectual content: Mönkemöller, Biester, Rohrer, Warncke, Hammersen, Holl.

    Statistical analysis: Kamrath, Holl.

    Supervision: Kamrath, Biester, Warncke, Holl.

    Conflict of Interest Disclosures: Dr Mönkemöller reported receiving personal fees from Medtronic outside the submitted work. Dr Biester reported receiving personal fees from Medtronic, Sanofi, Ypsomed, Novo Nordisk, AstraZeneca, DexCom, and Roche outside the submitted work. No other disclosures were reported.

    Funding/Support: The German Diabetes Prospective Follow-up Registry (DPV) is supported through the German Federal Ministry for Education and Research within the German Center for Diabetes Research (DZD, grant 82DZD14A02). Further financial support was received by the German Robert Koch Institute (RKI, diabetes surveillance) and the German Diabetes Association (DDG).

    Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

    Additional Contributions: We thank Katharina Fink (Institute of Epidemiology and Medical Biometry [ZIBMT], Ulm University, Ulm, Germany), Klemens Raile, MD, PhD (Department of Pediatric Endocrinology and Diabetology, Charité, University Medicine Berlin, Germany), and Angeliki Pappa, MD (Department of Pediatrics, University Hospital RWTH Aachen, Aachen, Germany), for their contribution to this work for methodology (Ms Fink), data analysis (Ms Fink), data collection (Drs Raile and Pappa), scientific discussion of the results (Ms Fink and Drs Raile and Pappa), and editing of the manuscript (Ms Fink and Drs Raile and Pappa). Andreas Hungele and Ramona Ranz developed the DPV software, Esther Bollow aggregated the DPV data, and Alexander Eckert, MSc, helped with the analysis (all clinical data managers, Ulm University). We thank Marianne Rohrer (Homburg) for language editing. None of the persons named received compensation for their contributions. We thank all centers participating in the DPV initiative (a list is available at www.d-p-v.eu).

    References
    1.
    Baum  A, Schwartz  MD.  Admissions to Veterans Affairs hospitals for emergency conditions during the COVID-19 pandemic.   JAMA. 2020;324(1):96-99. doi:10.1001/jama.2020.9972PubMedGoogle ScholarCrossref
    2.
    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(8):1530-1541. doi:10.1007/s00125-020-05152-1PubMedGoogle ScholarCrossref
    3.
    Karges  B, Schwandt  A, Heidtmann  B,  et al.  Association of insulin pump therapy vs insulin injection therapy with severe hypoglycemia, ketoacidosis, and glycemic control among children, adolescents, and young adults with type 1 diabetes.   JAMA. 2017;318(14):1358-1366. doi:10.1001/jama.2017.13994PubMedGoogle ScholarCrossref
    4.
    Lazzerini  M, Barbi  E, Apicella  A, Marchetti  F, Cardinale  F, Trobia  G.  Delayed access or provision of care in Italy resulting from fear of COVID-19.   Lancet Child Adolesc Health. 2020;4(5):e10-e11. doi:10.1016/S2352-4642(20)30108-5PubMedGoogle ScholarCrossref
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