Abstract / Summary
Diabetic bladder dysfunction (DBD) includes storage abnormalities and voiding dysfunction, but its clinical and experimental phenotypes do not follow a uniform chronological sequence. The urothelium is a urine barrier and a mechanosensory, paracrine, and inflammatory interface. Early diabetes may cause urothelial shedding, barrier permeability, abnormal ATP release, and altered sensory receptors. With longer disease duration, superficial architecture and some barrier properties may recover, while sensory and paracrine abnormalities persist. In parallel, impaired afferent conduction, reduced detrusor contractility, and extracellular matrix remodeling may become prominent, so local urothelial changes do not necessarily track whole-bladder function. Metabolic and oxidative stress, NLRP3-associated inflammation and pyroptosis, ferroptosis, and epigenetic and post-transcriptional regulation may contribute to urothelial injury, although evidence differs in cell specificity and disease-course localization. This review integrates clinical, animal, and cellular studies to examine urothelial barrier, sensory, paracrine, and cell-fate changes across DBD functional states, appraise the supporting molecular evidence and its limitations, and discuss the clinical relevance of urothelial biomarkers and therapeutic targets.