Diabetes mellitus is a chronic metabolic disease, posing a considerable threat to global public health. Treating systemic comorbidities has been one of the greatest clinical challenges in the management of diabetes. Diabetic bladder dysfunction, characterized by detrusor overactivity during the early stage of the disease and detrusor underactivity during the late stage, is a common urological complication of diabetes. Oxidative stress is thought to trigger hyperglycaemia-dependent tissue damage in multiple organs; thus, a growing body of literature has suggested a possible link between functional changes in urothelium, muscle and the corresponding innervations. Improved understanding of the mechanisms of oxidative stress could lead to the development of novel therapeutics to restore the redox equilibrium and scavenge excessive free radicals to normalize bladder function in patients with diabetes.
Oxidative stress, characterized by either excessive reactive oxygen species production or disturbed antioxidant regulation, occurs in biological systems in normal and pathological conditions.
In physiological conditions, reactive oxygen species have a crucial role in cell metabolism, proliferation, differentiation, inflammatory response and preservation of mitochondrial function.
The balance between oxidants and antioxidants is maintained through several intertwined mechanisms that could be vulnerable to hyperglycaemia, leading to dysregulated oxidative stress and diabetic complications.
Diabetic bladder dysfunction (DBD) can manifest with functional abnormalities varying over time, characterized by a sensory urgency in the early stage, and an impaired sensation of bladder fullness and impaired bladder emptying in the late stage.
Hyperglycaemia-induced oxidative stress leading to DBD might also be responsible for impaired contractility of smooth muscle, altered sensory response of urothelium, and slowed conduction of lower urinary tract innervation.
In-depth research on dysregulated mechanisms of oxidative stress will facilitate the development of novel treatments targeting deficient pathways to mitigate DBD.
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The authors declare no competing interests.
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- Sensory urgency
Increased perceived bladder sensation during filling, with a low bladder capacity and a short voiding duration.
- Daytime frequency
Micturition occurring more frequently during waking hours than previously deemed normal by the patient (defined by the International Urogynecological Association/International Continence Society).
- Pressure flow urodynamic testing
Refers to the voiding part during a urodynamic test, in which bladder pressure is measured simultaneously with the urinary flow.
- Clean intermittent catheterization
A method of draining the urine out of the bladder using a thin, soft tube, which is removed immediately once the bladder is emptied.
- Timed voiding
To void at fixed time intervals, instead of relying on the sensation of bladder fullness.
- Double voiding
To pass urine more than once during each void with the purpose of reducing residual volume.
- Antioxidant response element
(ARE). Transcription regulators acting with nuclear factor erythroid 2-related factor 2 to restore redox homeostasis and to activate cytoprotection in response to oxidative stress.
- Streptozotocin (STZ)-induced rat model
An animal model of type 1 diabetes induced by intravenous injection of streptozotocin to cause pancreatic islet β cell destruction.
- International Prostatic Symptom Score
A questionnaire containing seven items to assess the severity of lower urinary tract symptoms in male patients.
- Threshold pressure
The pressure recorded just before the onset of voiding during cystometry.
- Cystometric contraction pressure
Calculated by subtracting threshold pressure from the maximum pressure recorded during micturition.
- Swollen mitochondria
A hallmark of mitochondrial dysfunction and cell death, which can be characterized by the opening of permeability transition pores.
The complete collection of low-molecular weight metabolites, participating in the metabolic reactions to maintain cell physiological functions.
A transmembrane protein that forms a receptor complex with p75 neurotrophin receptor, binding with a precursor of nerve growth factor at the cell surface.
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Song, QX., Sun, Y., Deng, K. et al. Potential role of oxidative stress in the pathogenesis of diabetic bladder dysfunction. Nat Rev Urol 19, 581–596 (2022). https://doi.org/10.1038/s41585-022-00621-1