Inflammatory and endothelial host responses in community-acquired pneumonia: exploring the relationships with HbA1c, admission plasma glucose, and glycaemic gap—a cross-sectional study

Arnold Matovu Dungu*, Agnete Troen Lundgaard, Camilla Koch Ryrsø, Maria Hein Hegelund, Andreas Vestergaard Jensen, Peter Lommer Kristensen, Rikke Krogh-Madsen, Daniel Faurholt-Jepsen, Sisse Rye Ostrowski, Karina Banasik, Birgitte Lindegaard

*Corresponding author af dette arbejde

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Abstract

Introduction: Diabetes is associated with dysregulated immune function and impaired cytokine release, while transient acute hyperglycaemia has been shown to enhance inflammatory cytokine release in preclinical studies. Although diabetes and acute hyperglycaemia are common among patients with community-acquired pneumonia (CAP), the impact of chronic, acute, and acute-on-chronic hyperglycaemia on the host response within this population remains poorly understood. This study investigated whether chronic, acute, and acute-on- chronic hyperglycaemia are associated with distinct mediators of inflammatory, endothelial, and angiogenic host response pathways in patients with CAP.

Methods: In a cross-sectional study of 555 patients with CAP, HbA1c, admission plasma (p)-glucose, and the glycaemic gap (admission p-glucose minus HbA1c- derived average p-glucose) were employed as measures of chronic, acute, and acute-on-chronic hyperglycaemia, respectively. Linear regression was used to model the associations between the hyperglycaemia measures and 47 proteins involved in inflammation, endothelial activation, and angiogenesis measured at admission. The models were adjusted for age, sex, CAP severity, pathogen, immunosuppression, comorbidity, and body mass index. Adjustments for multiple testing were performed with a false discovery rate threshold of less than 0.05.

Results: The analyses showed that HbA1c levels were positively associated with IL-8, IL-15, IL-17A/F, IL-1RA, sFlt-1, and VEGF-C. Admission plasma glucose was also positively associated with these proteins and GM-CSF. The glycaemic gap was positively associated with IL-8, IL-15, IL-17A/F, IL-2, and VEGF-C.

Conclusion: In conclusion, chronic, acute, and acute-on-chronic hyperglycaemia were positively associated with similar host response mediators. Furthermore, acute and acute-on-chronic hyperglycaemia had unique associations with the inflammatory pathways involving GM-CSF and IL-2, respectively.
OriginalsprogEngelsk
Artikelnummer1372300
TidsskriftFrontiers in Immunology
Vol/bind15
Antal sider12
ISSN1664-3224
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Financial support for this study was provided by the Research Council at Copenhagen University Hospital, North Zealand, Grosserer L. F. Foghts Fond, Olga Bryde Nielsens Fond, Helen Rudes Fond, Kaptajnl\u00F8jtnant Harald Jensens og Hustrus Fond, and Fonden til L\u00E6gevidenskabens Fremme. The study\u2019s funders did not impact the study design, data collection, data analysis, interpretation, manuscript writing, or publication decision.

Publisher Copyright:
Copyright © 2024 Dungu, Lundgaard, Ryrsø, Hegelund, Jensen, Kristensen, Krogh-Madsen, Faurholt-Jepsen, Ostrowski, Banasik and Lindegaard.

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