Research question
Type 2 diabetes (T2DM) has become a global public health problem, with emerging evidence linking poor glycemic control to severe Klebsiella pneumoniae infections. Despite clinical observations of invasive syndromes in Asian T2DM populations, the dose-response relationship between glycemic variability and infection susceptibility remains uncharacterized.
Objective
This study aims to quantify how glycemic fluctuations modulate K. pneumoniae infection risk through multi-omics analysis of UK Biobank cohorts, integrating HbA1c trajectories with metabolomic, proteomic, and genomic data to identify causal thresholds for bacterial dissemination and host-pathogen molecular drivers.
Scientific rationale
Infectious complications are closely associated with poor glycemic control, chronic comorbidities, and immune dysfunction. Increasing evidence suggests that diabetes predisposes individuals to Klebsiella pneumoniae colonization and invasive infections, although the dose-dependent relationship between glycemic fluctuations and infection risk remains insufficiently characterized.
Hyperglycemia impairs neutrophil chemotaxis and phagocytosis while enhancing pro-inflammatory cytokine production, particularly interleukin-6 (IL-6), creating a self-reinforcing cycle of metabolic dysfunction and infection susceptibility. Clinically, acute K. pneumoniae infections can further destabilize glycemic control, underscoring a bidirectional relationship between infection and diabetes. As an opportunistic enteric pathogen, K. pneumoniae transitions to a virulent state in the context of intestinal dysbiosis. Chronic inflammation in diabetes compromises intestinal barrier integrity and promotes Enterobacteriaceae overgrowth, facilitating bacterial translocation. We hypothesize that persist.
