From Glucotoxicity to Lung Injury: Emerging Perspectives on Diabetes-Associated Respiratory Complications.

Abstract

Emerging evidence highlights glucose toxicity as a pivotal driver of diabetic respiratory complications, characterized by hyperglycemia-induced metabolic dysregulation and multi-organ damage. The lung, a metabolically active organ, exhibits unique susceptibility to glucose toxicity due to its exposure to oxidative stress, inflammatory cascades, and disrupted metabolic reprogramming, particularly in glycolysis and mitochondrial dysfunction. Diabetes-associated respiratory complications encompass increased susceptibility to respiratory infections, acute respiratory distress syndrome (ARDS) with macrophage-driven glycolytic shifts, and gestational diabetes mellitus (GDM)-associated fetal lung dysplasia via impaired epithelial differentiation. Future research should prioritize metabolic dysregulation-targeted therapies, gut-lung axis modulation, and personalized approaches to address the interplay between hyperglycemia, oxidative stress, and immune dysregulation. Elucidating genetic and epigenetic modifiers of glucotoxicity will further advance therapeutic strategies for diabetes-associated pneumopathy. This review provides an overview of epidemiological burden, lung structural and functional changes, pathophysiological mechanisms, clinical outcomes and complications, therapeutic and preventive strategies, unanswered questions, and future directions of diabetes-associated respiratory complications.