Mechanisms of Action for Diabetic Bladder Dysfunction — State of the Art

Abstract

Purpose of Review Diabetes (DM) is a common cause of lower urinary tract symptoms (LUTS), known as diabetic bladder dysfunction (DBD). The phenotype for DBD is described in the literature with considerable heterogeneity and includes poor sensation, increased compliance, detrusor underactivity, urinary retention, weak stream, hesitancy, but also urgency incontinence, and, for many, detrusor overactivity. Progress has been made in understanding DBD, yet a unified phenotype or classification system for DBD remains elusive. Much remains unknown about the underlying mechanisms. Recent Findings No classification scheme to phenotype DBD has been proposed. Evidence from recent literature suggests four primary drivers: detrusor smooth muscle dysfunction, urothelial dysfunction, autonomic neurologic dysfunction, and circulating and systemic factors such as inflammation, oxidative stress, and microvascular damage. It is likely that these drivers have multi-factorial causes and inter-relate in complex ways. Recent findings in animal models lend new support to detrusor smooth muscle dysfunction as well as inflammation. Reports utilizing next-generation sequencing have begun to appear in the DBD literature and promise further insight. Summary DBD currently lacks a unified classification scheme and a clear mechanism. The advent of new, more translatable large animal models and next-generation sequencing promises many exciting new tools and models that more closely translate to human disease.

Association of detrusor underactivity with aging and metabolic syndrome: suggestions from animal models

“…Animal models of types 1 and 2 diabetes mellitus exhibit detrusor underactivity. These features in animal models correspond to some in human patients with detrusor underactivity who have reduced bladder sensation and increased postvoiding residual urine volume ( 5 , 6 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ). These models also show increased bladder weight, inflammatory cell infiltration, and collagen deposition in the bladder ( 5 , 6 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ).…”

“…Diabetes mellitus causes lower urinary tract dysfunction in humans through peripheral neuropathy and muscle injury ( 5 , 6 , 21 , 22 ). This is characterized by impaired bladder sensation and emptying, increased bladder capacity and postvoiding residual urine volume, decreased detrusor contractility, and a detrusor underactivity-like urodynamic phenotype ( 5 , 6 , 21 , 22 ). The pathophysiology of diabetic bladder dysfunction is multifactorial and includes detrusor muscle and urothelial dysfunction, as well as neuronal damage ( 5 , 6 , 21 , 22 ).…”

“…This is characterized by impaired bladder sensation and emptying, increased bladder capacity and postvoiding residual urine volume, decreased detrusor contractility, and a detrusor underactivity-like urodynamic phenotype ( 5 , 6 , 21 , 22 ). The pathophysiology of diabetic bladder dysfunction is multifactorial and includes detrusor muscle and urothelial dysfunction, as well as neuronal damage ( 5 , 6 , 21 , 22 ). Altered glucose metabolism, oxidative stress, and autonomic neuropathy have been implicated in the development of diabetes mellitus associated with bladder dysfunctions such as detrusor underactivity ( 5 , 6 , 14 , 15 , 21 ).…”

“…The early and late phases of diabetes mellitus result in compensated (such as detrusor overactivity) and decompensated (such as detrusor underactivity) bladder functions, respectively ( 5 , 6 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ). The timing of the onset of detrusor underactivity and abnormalities in urinary parameters varies among different diabetic models.…”

“…Metabolic syndrome has also been associated with lower urinary tract dysfunction in both males and females ( 11 , 12 , 13 ). Recently, several animal models of metabolic syndrome have been developed based on the bladder dysfunctions observed in human patients with detrusor underactivity ( 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ). Therefore, this review discusses the association between metabolic syndrome and detrusor underactivity in old animal models.…”