Pre-Existing Diabetes and COVID-Associated Hyperglycaemia in Patients with COVID-19 Pneumonia

  1. Andrea Laurenzi
  2. Amelia Caretto
  3. Chiara Molinari
  4. Elena Bazzigaluppi
  5. Cristina Brigatti
  6. Ilaria Marzinotto
  7. Alessia Mercalli
  8. Raffaella Melzi
  9. Rita Nano
  10. Cristina Tresoldi
  11. Giovanni Landoni
  12. Fabio Ciceri
  13. Vito Lampasona
  14. Marina Scavini
  15. Lorenzo Piemonti

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Abstract

Aim. The aim of the current study was to compare clinical characteristics, laboratory findings, and major outcomes of patients hospitalized for COVID-19 pneumonia with COVID-associated hyperglycaemia or pre-existing diabetes. Methods. A cohort of 176 adult patients with a diagnosis of pre-existing diabetes (n = 112) or COVID-associated hyperglycaemia (n = 55) was studied. Results. Patients with COVID-associated hyperglycaemia had lower BMI, significantly less comorbidities, and higher levels of inflammatory markers and indicators of multi-organ injury than those with pre-existing diabetes. No differences between pre-existing diabetes and COVID-associated hyperglycaemia were evident for symptoms at admission, the humoral response against SARS-CoV-2, or autoantibodies to glutamic acid decarboxylase or interferon alpha-4. COVID-associated hyperglycaemia was independently associated with the risk of adverse clinical outcome, which was defined as ICU admission or death (HR 2.11, 95% CI 1.34–3.31; p = 0.001), even after adjustment for age, sex, and other selected variables associated with COVID-19 severity. Furthermore, at the same time, we documented a negative association (HR 0.661, 95% CI 0.43–1.02; p = 0.063) between COVID-associated hyperglycaemia to swab negativization. Conclusions. Recognizing hyperglycaemia as a specific clinical entity associated with COVID-19 pneumonia is relevant for early and appropriate patient management and close monitoring for the progression of disease severity.

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  1. Version published to 10.3390/biology10080754
  2. Version published to 10.1101/2021.04.17.21255548v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.04.17.21255548: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: The study was approved by the local Institutional Review Board (protocol n 34/int/2020; NCT04318366) and all patients signed a written informed consent.
    Consent: The study was approved by the local Institutional Review Board (protocol n 34/int/2020; NCT04318366) and all patients signed a written informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    BlindingData were verified by data managers and clinicians for accuracy and crosschecked in blind.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Specific antibodies to different SARS-CoV-2 antigens, interferon alpha-4 and glutamic acid decarboxylase (GAD) were tested by a luciferase immunoprecipitation system (LIPS) assay, as previously described (11).
    glutamic acid decarboxylase (GAD)
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analyses were performed with the SPSS 24 (SPSS Inc. /IBM) and the R software version 3.4.0 (R Core Team (2020).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study has some limitations. First, the analysis was performed on a subcohort of 176 patients selected for having hyperglycemia (either new-onset or preexisting diabetes) out of 584 subjects of our original cohort (12). All patients with diabetes were included, and as for age, sex, new-onset diabetes prevalence, and the clinical outcome of our cohort appears superimposable to those reported by many authors. Despite this, we cannot exclude a selection bias. Second, our cohort is limited to hospitalized patients with COVID-19 pneumonia. Third, we only assessed fasting blood glucose and we acknowledge that more specific indicators of beta cell function, such as serum insulin and or C peptide levels, should have been measured. Fourth, the lack of HbA1c measurements in our cohort is a limitation. The evidence of normal HbA1c at the time of admission would indicate no history of recent hyperglycemia and confirm the diagnosis of new-onset diabetes. HbA1c levels were available for some patients with preexisting diabetes (51 (41-58) mmol/mol; 6.8%), but in very few patients with new-onset diabetes (38 (36-40) mmol/mol; 5.6%), and for this reason were not included in the analysis. In conclusion, new-onset diabetes/hyperglycemia is emerging as a complication of COVID-19 pneumonia and this clinical entity still needs to be adequately characterized in comparison with preexisting diabetes. It is clear from our study that patients with new-onset diabetes had increased levels of inflammat...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04318366RecruitingCOVID-19 Patients Characterization, Biobank, Treatment Respo…

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2021.04.17.21255548v1 on medRxiv