Sepsis is a major cause of morbidity and mortality worldwide and is characterized by dysregulated immune responses and profound metabolic alterations. Experimental studies suggest that altered glucose metabolism in immune cells contributes to immune dysfunction and excessive inflammation; however, population-level evidence linking metabolic status to immune-related clinical outcomes in sepsis remains limited.
This study aims to investigate the association between systemic glucose metabolism-related biomarkers and immune-related clinical outcomes in individuals with sepsis using data from the UK Biobank. Specifically, we will examine whether baseline metabolic traits (including fasting glucose, HbA1c, lipid profiles, and body composition measures) and genetic susceptibility variants are associated with the incidence of sepsis and sepsis-related mortality.
In addition, we will explore the relationship between metabolic markers, inflammatory protein biomarkers, and routinely measured blood cell indices (such as leukocyte subsets), which may serve as indicators of immune status in large-scale epidemiological data. By integrating metabolic, genetic, and proteomic clinical data, we aim to identify metabolic profiles associated with adverse immune-related outcomes in sepsis.
Statistical analyses will include multivariable regression and time-to-event models adjusting for relevant demographic, lifestyle, and clinical covariates. Sensitivity analyses will be performed to assess the robustness of findings across subgroups.
The results of this study will provide population-based evidence on the role of systemic metabolic status in sepsis susceptibility and outcomes, and will generate hypotheses to inform future mechanistic and experimental studies on immune-metabolic regulation.