Time-Dependent Changes of Urethral Function in Diabetes Mellitus: A Review

This article reviewed the current knowledge on time-course manifestation of diabetic urethral dysfunction (DUD), and explored an early intervention target to prevent the contribution of DUD to the progression of diabetes-induced impairment of the lower urinary tract (LUT). In the literature search through PubMed, key words used included "diabetes mellitus," "diabetic urethral dysfunction," and "diabetic urethropathy." Polyuria and hyperglycemia induced by diabetes mellitus (DM) can cause the time-dependent changes in functional and morphological manifestations of DUD. In the early stage, it promotes urethral dysfunction characterized by increased urethral pressure during micturition. However, the detrusor muscle of the bladder tries to compensate for inducing complete voiding by increasing the duration and amplitude of bladder contractions. As the disease progresses, it can induce an impairment of coordinated micturition due to dyssynergic activity of external urethra sphincter, leading to detrusor-sphincter dyssynergia. The impairment of relaxation mechanisms of urethral smooth muscles (USMs) may additionally be attributable to decreased responsiveness to nitric oxide, as well as increased USM responsiveness to α1-adrenergic receptor stimulation. In the late stage, diabetic neuropathy may play an important role in inducing LUT dysfunction, showing that the decompensation of the bladder and urethra, which can cause the decrease of voiding efficiency and the reduced thickness of the urothelium and the atrophy of striated muscle bundles, possibly leading to the vicious cycle of the LUT dysfunction. Further studies to increase our understandings of the functional and molecular mechanisms of DUD are warranted to explore potential targets for therapeutic intervention of DM-induced LUT dysfunction.