Pre-Existing Diabetes Alters Pulmonary Inflammatory Gene Expression Priming for Injury

Abstract

Diabetes mellitus (DM) is a systemic disease known for its cardiovascular complications, but its impact on pulmonary health remains underexplored. We aimed to determine how pre-existing DM influences lung inflammation and susceptibility to acute lung injury (ALI). RNA sequencing was performed on lung tissues from streptozotocin-induced DM and non-DM mouse lungs, followed by gene enrichment and bioinformatics analysis. Lung inflammation and injury were assessed in a lipopolysaccharide-induced sepsis model using Wet/Dry lung weight ratios, histopathology, RT-qPCR, and cytokine profiling. Transcriptomic analysis revealed that DM lungs exhibited upregulated inflammatory pathways and signs of compromised endothelial barrier integrity. While LPS exposure induced lung inflammation, no additive or synergistic effect of DM and LPS was observed in exacerbating lung injury. However, DM alone was associated with increased expression of inflammatory cytokines (TNF-α, IL-1β, MCP-1, and CXCL-1), greater fluid accumulation, and structural lung changes indicative of enhanced baseline susceptibility to ALI. These findings underscore the impact of DM on priming the lung for inflammation and injury and suggest that targeting DM-associated molecular pathways may help mitigate pulmonary complications in diabetic individuals.