TY - JOUR

T1 - Inflammatory and endothelial host responses in community-acquired pneumonia

T2 - exploring the relationships with HbA1c, admission plasma glucose, and glycaemic gap—a cross-sectional study

AU - Dungu, Arnold Matovu

AU - Lundgaard, Agnete Troen

AU - Ryrsø, Camilla Koch

AU - Hegelund, Maria Hein

AU - Jensen, Andreas Vestergaard

AU - Kristensen, Peter Lommer

AU - Krogh-Madsen, Rikke

AU - Faurholt-Jepsen, Daniel

AU - Ostrowski, Sisse Rye

AU - Banasik, Karina

AU - Lindegaard, Birgitte

N1 - Publisher Copyright: Copyright © 2024 Dungu, Lundgaard, Ryrsø, Hegelund, Jensen, Kristensen, Krogh-Madsen, Faurholt-Jepsen, Ostrowski, Banasik and Lindegaard.

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - admission p-glucose

KW - community-acquired pneumonia

KW - glycaemic gap

KW - glycated haemoglobin (HbA1c)

KW - host response mediators

KW - hyperglycaemia

U2 - 10.3389/fimmu.2024.1372300

DO - 10.3389/fimmu.2024.1372300

M3 - Journal article

C2 - 38840922

AN - SCOPUS:85195104379

VL - 15

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 1372300

ER -