Residents and Fellows Research in Progress
Sunday, October 13, 2024
12:45 PM–02:15 PM
Abstract
Introduction: Diabetes mellitus is a common comorbidity in acute lung injury (ALI) patients. Despite its well-established prevalence and impact on the cardiovascular system, kidneys, and retina, our knowledge of the lung as a target organ in diabetes is limited, heavily relying on inconsistent findings derived primarily from observational data.
Research Question or Hypothesis: How does diabetes impact the lungs and outcomes of ALI, and what are the underlying mechanisms involved?
Study Design: Incorporating clinical, animal, and cellular studies, we performed a comprehensive investigation into the effects of diabetes on the lungs and ALI outcomes.
Methods: Fluids and Catheters Treatment Trial datasets and plasma samples were used to examine the impact of pre-existing diabetes on ALI patients. While the effect of advanced glycation end-products (AGE) was tested on human lung endothelial (ECs) and epithelial cells, the effect of diabetes on mouse lungs (injury and edema) was tested on 8, 12, and 24-week streptozotocin-administered mice. Proteomic and cytokine analyses of the diabetes mouse lungs were performed for mechanistic characterization. Statistical analysis was conducted using GraphPad Prism.
Results: Our clinical data revealed that ALI patients with diabetes experienced significantly poorer outcomes, including lower survival rates and prolonged hospital and ICU stays, alongside elevated levels of pro-inflammatory markers. In our experimental animal studies, diabetic mice exhibited lung inflammation and edema, with an increased risk of worsening ALI. In vitro studies demonstrated that AGEs altered the tight junction proteins that regulate permeability, cytokines, and AKT and P38 MAP Kinase activity.
Conclusion: Clinical and experimental data indicate that diabetes significantly exacerbates lung inflammation and worsens ALI outcomes via expression modulation of tight junction proteins, cytokines, and the activation of key inflammatory pathways.
Presenting Author
Abdulaziz Alanazi PharmD,MSUniversity of Georgia
Authors
Priya Narayanan Ph.D.
University of Georgia College of Pharmacy and Charlie Norwood VA Medical Center
Mohamed Selim B.Pharm
University of Georgia
Somanath Shenoy Ph.D. FAHA
University of Georgia
Andrea Sikora Newsome PharmD, MSCR, BCCCP, FCCM
Augusta University Medical Center/UGA College of Pharmacy
Duo Zhang Ph.D
University of Georgia