Metabolic Syndrome and Overactive Bladder Syndrome May Share Common Pathophysiologies

Abstract

Metabolic syndrome (MetS) is defined by a group of cardiovascular risk factors, including impaired glucose tolerance, central obesity, hypertension, and dyslipidemia. Overactive bladder (OAB) syndrome consists of symptoms such as urinary urgency, frequency, and nocturia with or without urge incontinence. The high prevalences of metabolic syndrome (MetS) and overactive bladder (OAB) worldwide affect quality of life and cause profound negative impacts on the social economy. Accumulated evidence suggests that MetS might contribute to the underlying mechanisms for developing OAB, and MetS-associated OAB could be a subtype of OAB. However, how could these two syndromes interact with each other? Based on results of animal studies and observations in epidemiological studies, we summarized the common pathophysiologies existing between MetS and OAB, including autonomic and peripheral neuropathies, chronic ischemia, proinflammatory status, dysregulation of nutrient-sensing pathways (e.g., insulin resistance at the bladder mucosa and excessive succinate intake), and the probable role of dysbiosis. Since the MetS-associated OAB is a subtype of OAB with distinctive pathophysiologies, the regular and non-specific medications, such as antimuscarinics, beta-3 agonist, and botulinum toxin injection, might lead to unsatisfying results. Understanding the pathophysiologies of MetS-associated OAB might benefit future studies exploring novel biomarkers for diagnosis and therapeutic targets on both MetS and OAB.

Urinary ATP Levels Are Controlled by Nucleotidases Released from the Urothelium in a Regulated Manner

“…Voiding dysfunctions have been linked not only to diseases of the LUT, but also to systemic diseases such as diabetes [ 26 , 27 , 28 , 29 ], obesity [ 29 , 30 ], hyperlipidemia [ 31 , 32 ], and hypertension [ 33 , 34 , 35 ] or with metabolic syndrome that is defined by impaired glucose tolerance, central obesity, hypertension and dyslipidemia [ 36 , 37 , 38 ]. Metabolic syndrome and OAB may share common pathophysiology mechanisms [ 39 ] since patients with metabolic syndrome exhibit a higher incidence of OAB [ 40 ]. Impaired purinergic signaling in the bladder has been demonstrated in animal models of diabetes, dyslipidemia, obesity and hypertension [ 41 , 42 , 43 , 44 ] and, therefore, ATP and other purines might be involved in the development of voiding dysfunctions associated with systemic diseases, including the metabolic syndrome.…”

Vinpocetine Ameliorates Metabolic-Syndrome-Associated Bladder Overactivity in Fructose-Fed Rats by Restoring Succinate-Modulated cAMP Levels and Exerting Anti-Inflammatory Effects in the Bladder Detrusor Muscle

“…Our results are consistent with these findings, as they demonstrate the elevated succinate levels, bladder fibrosis, and impaired detrusor contractility in the fructose group. Metabolic inflammation may result in bladder fibrosis, which progresses to chronic inflammation, repeated wound healing, sustained collagen deposition, and extracellular matrix remodelling, gradually increasing the stuffiness of the bladder [ 7 ]. In this study, we found that both vinpocetine and celecoxib treatments provided anti-inflammatory effects to restore the fibrogenesis and detrusor function in FFRs.…”

“…Our study has several limitations. First, metabolic perturbations could deteriorate bladder function through several mechanisms, such as pelvis ischemia, neuropathy, insulin resistance, and excessive succinate production [ 7 ]. In the present study, we focussed on the protective actions of vinpocetine on the succinate-modulated bladder dysfunction of the deficiency in detrusor cAMP and proinflammation.…”

“…The high global prevalence of OAB causes a public health burden due to the detrimental effects on the quality of life and productivity of patients, particularly when the effective treatments for specific subtypes of OAB remain elusive [ 3 , 4 ]. Accumulative evidence suggests that MetS and OAB could share common pathophysiologies, such as dysregulated nutrient-sensing pathways (e.g., insulin resistance in the bladder mucosa [ 5 ] and excessive succinate intake [ 6 ]), chronic ischemia, and proinflammatory status [ 7 ]. Furthermore, the MetS-associated OAB is an important subtype of OAB, which could not be well managed by nonspecific pharmacotherapies (e.g., antimuscarinics, β-3 agonist, and botulinum toxin injections) [ 4 ].…”

Editorial Comment to Predictive factors of de novo overactive bladder in clinically localized prostate cancer patients after robot‐assisted radical prostatectomy

“…The possibility of the metabolic syndrome's involvement in the pathogenesis of OAB has been reported 5 . The results of the preoperative questionnaires and UDS showed a trend toward poorer storage and voiding symptoms and function in the de novo OAB group, although neither was statistically significant and the body mass index (BMI), which was listed as a risk factor, may have had an effect 3 .…”