The Pharmacological Mechanism of Diabetes Mellitus-Associated Overactive Bladder and Its Treatment with Botulinum Toxin A

Overview

Journal Toxins (Basel)

Publisher MDPI

Specialty Toxicology

Date 2020 Mar 20

PMID 32188046

Citations 8

Authors

Chung-Cheng Wang

Yung-Hong Jiang

Hann-Chorng Kuo

Affiliations

Soon will be listed here.

Abstract

Diabetes mellitus (DM) is an independent risk factor for overactive bladder (OAB). The pathophysiology of DM-associated OAB is multifactorial and time-dependent. Diabetic bladder dysfunction is highly associated with diabetic complications, mainly including diabetic neuropathy and atherosclerosis. Chronic systemic inflammation and bladder urothelial inflammation may contribute to the onset of OAB. Intravesical botulinum toxin A (BoNT-A) injection has proved to be a successful treatment for idiopathic and neurogenic OAB. BoNT-A can inhibit the efferent pathways of the bladder as well as the chronic inflammation and hypersensitivity via the afferent pathways. We conducted a review of the published literature in Pubmed using a combination of two keywords, namely "botulinum toxin A" (BoNT-A) and "overactive bladder", with or without the additional keywords "detrusor overactivity", "diabetes mellitus", "inflammation", and "urodynamic study". We also reviewed the experience of our research teams, who have published several studies of the association between DM and OAB. Since limited data support the effectiveness and safety of BoNT-A for treating patients with DM-associated OAB, a comprehensive evaluation of diabetic complications and urodynamic study is needed before treatment. In the future, it is imperative to explore the clinical characteristics and inflammatory biomarkers of diabetes as determining predictors of the treatment efficacy.

Citing Articles

Evaluating the Efficacy and Safety of Botulinum Toxin in Treating Overactive Bladder in the Elderly: A Meta-Analysis with Trial Sequential Analysis of Randomized Controlled Trials.

Chen Y, Kuo J, Huang Y, Lai P, Ou Y, Lin Y Toxins (Basel). 2024; 16(11).

PMID: 39591239 PMC: 11597992. DOI: 10.3390/toxins16110484.

Association of healthy eating index-2015 and overactive bladder: a cross-sectional study.

Hao X, Liu G, Li D Front Nutr. 2024; 11:1400398.

PMID: 39355559 PMC: 11442424. DOI: 10.3389/fnut.2024.1400398.

The association between overactive bladder and systemic immunity-inflammation index: a cross-sectional study of NHANES 2005 to 2018.

Wei B, Zhao Y, Lin P, Qiu W, Wang S, Gu C Sci Rep. 2024; 14(1):12579.

PMID: 38822015 PMC: 11143340. DOI: 10.1038/s41598-024-63448-3.

Association between life's essential 8 and overactive bladder.

Feng G, Huang S, Zhao W, Gong H Sci Rep. 2024; 14(1):11842.

PMID: 38783031 PMC: 11116455. DOI: 10.1038/s41598-024-62842-1.

Diabetes mellitus, systemic inflammation and overactive bladder.

He Q, Wu L, Deng C, He J, Wen J, Wei C Front Endocrinol (Lausanne). 2024; 15:1386639.

PMID: 38745959 PMC: 11091467. DOI: 10.3389/fendo.2024.1386639.

References

Wang C, Nagatomi J, Toosi K, Yoshimura N, Hsieh J, Chancellor M . Diabetes-induced alternations in biomechanical properties of urinary bladder wall in rats. Urology. 2009; 73(4):911-5. PMC: 2728502. DOI: 10.1016/j.urology.2008.11.026. View

Lee W, Wu H, Huang K, Wu H, Yu H, Wu C . Hyposensitivity of C-fiber afferents at the distal extremities as an indicator of early stages diabetic bladder dysfunction in type 2 diabetic women. PLoS One. 2014; 9(1):e86463. PMC: 3900526. DOI: 10.1371/journal.pone.0086463. View

Xiao N, Wang Z, Huang Y, Daneshgari F, Liu G . Roles of polyuria and hyperglycemia in bladder dysfunction in diabetes. J Urol. 2012; 189(3):1130-6. PMC: 4104602. DOI: 10.1016/j.juro.2012.08.222. View

Wang C, Kuo H . Urothelial Dysfunction and Chronic Inflammation in Diabetic Patients with Overactive Bladder. Low Urin Tract Symptoms. 2016; 9(3):151-156. DOI: 10.1111/luts.12126. View

Wang C, Lee C, Kuo H . Efficacy and Safety of Intravesical OnabotulinumtoxinA Injection in Patients with Detrusor Hyperactivity and Impaired Contractility. Toxins (Basel). 2016; 8(3). PMC: 4810227. DOI: 10.3390/toxins8030082. View

Majima T, Matsukawa Y, Funahashi Y, Takai S, Kato M, Yamamoto T . Urodynamic analysis of the impact of diabetes mellitus on bladder function. Int J Urol. 2019; 26(6):618-622. DOI: 10.1111/iju.13935. View

Ha U, Park E, Kim J . Effect of botulinum toxin on expression of nerve growth factor and transient receptor potential vanilloid 1 in urothelium and detrusor muscle of rats with bladder outlet obstruction-induced detrusor overactivity. Urology. 2011; 78(3):721.e1-721.e6. DOI: 10.1016/j.urology.2011.03.070. View

Wang C, Chancellor M, Lin J, Hsieh J, Yu H . Type 2 diabetes but not metabolic syndrome is associated with an increased risk of lower urinary tract symptoms and erectile dysfunction in men aged <45 years. BJU Int. 2009; 105(8):1136-40. DOI: 10.1111/j.1464-410X.2009.08913.x. View

Papagiannopoulou D, Vardouli L, Dimitriadis F, Apostolidis A . Retrograde transport of radiolabelled botulinum neurotoxin type A to the CNS after intradetrusor injection in rats. BJU Int. 2015; 117(4):697-704. DOI: 10.1111/bju.13163. View

10.

Tong Y, CHIN W, Cheng J . Alterations in urinary bladder M2-muscarinic receptor protein and mRNA in 2-week streptozotocin-induced diabetic rats. Neurosci Lett. 2000; 277(3):173-6. DOI: 10.1016/s0304-3940(99)00871-x. View

11.

Chiu A, Huang M, Wang C, Kuo H . Higher glycosylated hemoglobin levels increase the risk of overactive bladder syndrome in patients with type 2 diabetes mellitus. Int J Urol. 2012; 19(11):995-1001. DOI: 10.1111/j.1442-2042.2012.03095.x. View

12.

Xu D, Zhao M, Huang L, Wang K . Overactive bladder symptom severity, bother, help-seeking behavior, and quality of life in patients with type 2 diabetes: a path analysis. Health Qual Life Outcomes. 2018; 16(1):1. PMC: 5749008. DOI: 10.1186/s12955-017-0829-z. View

13.

Akaike N, Shin M, Wakita M, Torii Y, Harakawa T, Ginnaga A . Transsynaptic inhibition of spinal transmission by A2 botulinum toxin. J Physiol. 2012; 591(4):1031-43. PMC: 3591713. DOI: 10.1113/jphysiol.2012.242131. View

14.

Szasz T, Wenceslau C, Burgess B, Nunes K, Webb R . Toll-Like Receptor 4 Activation Contributes to Diabetic Bladder Dysfunction in a Murine Model of Type 1 Diabetes. Diabetes. 2016; 65(12):3754-3764. PMC: 5127246. DOI: 10.2337/db16-0480. View

15.

Yeniel A, Ergenoglu A, Meseri R, Kismali E, Ari A, Kavukcu G . Is overactive bladder microvasculature disease a component of systemic atheroscleorosis?. Neurourol Urodyn. 2017; 37(4):1372-1379. DOI: 10.1002/nau.23452. View

16.

Chancellor M . The overactive bladder progression to underactive bladder hypothesis. Int Urol Nephrol. 2014; 46 Suppl 1:S23-7. DOI: 10.1007/s11255-014-0778-y. View

17.

Jackson R, Vittinghoff E, Kanaya A, Miles T, Resnick H, Kritchevsky S . Urinary incontinence in elderly women: findings from the Health, Aging, and Body Composition Study. Obstet Gynecol. 2004; 104(2):301-7. DOI: 10.1097/01.AOG.0000133482.20685.d1. View

18.

Lee W, Wu H, Tai T, Yu H, Chiang P . Investigation of urodynamic characteristics and bladder sensory function in the early stages of diabetic bladder dysfunction in women with type 2 diabetes. J Urol. 2008; 181(1):198-203. DOI: 10.1016/j.juro.2008.09.021. View

19.

Lucioni A, Bales G, Lotan T, McGehee D, Cook S, Rapp D . Botulinum toxin type A inhibits sensory neuropeptide release in rat bladder models of acute injury and chronic inflammation. BJU Int. 2008; 101(3):366-70. DOI: 10.1111/j.1464-410X.2007.07312.x. View

20.

Klee N, Moreland R, Kendig D . Detrusor contractility to parasympathetic mediators is differentially altered in the compensated and decompensated states of diabetic bladder dysfunction. Am J Physiol Renal Physiol. 2019; 317(2):F388-F398. PMC: 6732447. DOI: 10.1152/ajprenal.00178.2019. View