Current Treatment of Overactive Bladder in Patients with Diabetes and Obesity
A review and assessment of five current research studies for the efficacy in managing overactive bladder syndrome, particularly in patients with metabolic disease.
October 2019
Volume 1, Issue 8

Introduction

Overactive bladder syndrome (OAB) is defined as “urinary urgency, usually with urinary frequency and nocturia, with or without urgency urinary incontinence.”1 Overactive bladder syndrome is highly prevalent and may significantly impact patients' overall quality of life, including mental health and sleep patterns.2 In addition, OAB syndrome is associated with a substantial economic burden from both a societal and patient perspective.3

The impact may be even more pronounced in diabetic patients, where the prevalence of OAB exceeds that of the general population. By some estimates, the prevalence of overactive bladder in individuals with diabetes exceeds 20%, with over half of those patients developing urge continence.

Findings from a prospective, cross-sectional study of diabetics with OAB,4 suggest that the severity of OAB in this population is associated with several factors which have been confirmed in other studies:5-8

  • Diabetes duration > 10 years
  • Age > 50 years  
  • Symptomatic diabetic polyneuropathy
  • Diminished or absent ankle reflexes
  • High glycosylated hemoglobin levels   

Furthermore, the presence of severe erectile dysfunction appears to be significantly associated with OAB, especially OAB wet, in men with type 2 diabetes.9

Bladder dysfunction in the context of diabetes is a spectrum disorder and may range from detrusor (bladder) overactivity—frequently associated with OAB—to detrusor underactivity. Most clinicians are familiar with diabetic cystopathy, a neuropathic condition stemming from damage to visceral afferents in the detrusor that leads to elevated urinary post-void residuals, suboptimal detrusor contractility, and impaired sensation of fullness.10 However, by some estimates, OAB syndrome may be more prevalent than impaired contractility and emptying dysfunction in the patients with diabetes.11,12 

Some researchers have postulated that detrusor overactivity and underactivity are aspects of a continuum of diabetic bladder dysfunction, with early, hyperglycemia-induced polyuria causing myogenic and neurogenic damage and leading to an overactive bladder.13,14  With the chronic accumulation of toxic metabolites, detrusor function appears to decompensate, leading to the development of underactivity.

While obesity and its attendant increase in intra-abdominal pressure has been associated with pelvic conditions such as stress urinary incontinence,15 the relationship between OAB and obesity remains inconsistent. While some authors suggest that an increase in body mass index is associated with overactive bladder,16-18 other studies showed no association.19, 20

Furthermore, the potential improvement of the obesity-related mechanical damage to the pelvic floor after weight loss may seem logical, it is not entirely clear as to the reason that urgency urinary incontinence may also improve afterwards. In fact, Subak et al. showed that urgency urinary incontinence may improve similarly to stress urinary incontinence in women three years after bariatric surgery.21

More recently, the pendulum appears to be swinging in the direction of a relationship between obesity and lower urinary tract symptoms in women. Although the literature on metabolic syndrome, OAB, and lower urinary tract symptoms in women is limited, investigators from the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN),22 indicated an association between central and general obesity and OAB, particularly in older women. These observations have been confirmed by Bunn et al who conducted a meta-analysis demonstrating sufficient evidence of obesity as a factor of the metabolic syndrome both as a contributor and predictor of lower urinary tract symptoms in women.23

As many women who experience lower urinary tract symptoms are likely to be overweight and present with features of the metabolic syndrome, there is indeed an opportunity to discuss the added advantage of achieving weight loss as an adjunct in managing symptoms of overactive bladder.22  Indeed, patients with overweight and obesity, especially those with central obesity, should be screened for OAB and, if symptomatic, begin appropriate management.

The treatment options for OAB are the same for every patient. The American Urological Association/SUFU Guideline on the management of OAB suggests a step-wise approach with first-line therapy involving behavioral modification and other non-pharmaceutical, non-surgical measures.23  Second-line therapy involves pharmaceutical treatment with either anticholinergics or a β-3 adrenergic agonist, while third-line therapy involves neuromodulation or intravesical botulinum toxin A injection. 

A recent guideline amendment included combination therapy with an anticholinergic and β-3 adrenergic agonist for patients who were refractory to treatment with either drug class alone.24 Indeed, it is the benefits of combination therapy that comprise the conclusions of several of the manuscripts included in this review.25-27

As with many conditions, the addition of new medications and new combination regimens has been definitely welcome for the treatment of a chronic and bothersome condition. It is also important to consider that the addition of new medicine to a patient’s regimen may increase the risk of side effects and potential drug-drug interactions. While a β-3 adrenergic agonist is relatively well-tolerated, as demonstrated in the PREFER trials,25,27 the addition of this drug class does carry the potential for an increase in blood pressure and attendant increase in cost.

Several other factors should be taken into account when addressing overactive bladder syndrome in the patient with diabetes and other manifestations of metabolic syndrome, such as sex and age. Since we can anticipate that many patients who will present with OAB will be older, confounding conditions such as benign prostatic enlargement may play a role in symptom causality in men.

In older men, for example, a referral to a urologist for evaluation and subsequent employment of uroflowmetry and post-void residual volume determination may help guide therapy. In addition, the impact of polydipsia, polyuria, mobilization of lower extremity edema, and impairments in mobility in this population may all contribute to increased urine production and episodes of urge urinary incontinence. 

It is also important to note that pharmacologic agents such as diuretics, antihypertensives, and antidepressants may have a deleterious impact on bladder health. In the same vein, anticholinergic burden should be closely monitored, especially in the aging patient. Intuitively, the implementation of a β-3 adrenergic agonist such as mirabegron in this patient population should be strongly considered. 

In summary, while it is easy to view OAB as a “bladder problem,” the astute clinician will recognize the often-subtle interplay between urinary symptoms and other systemic conditions, making OAB a “body problem.”

 

Sources:

  1. Haylen BT, de Ridder D, Freeman RM, et al.  An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn. 2010; 29:4-20.
  2. Wang Y, Xu K, Hu H, et al. Prevalence, risk factors, and impact on health related quality of life of overactive bladder in China. Neurourol Urodyn. 2011; 30: 1448-1455.
  3. Coyne KS, Wein A, Nicholson S, et al.  Economic burden of urgency urinary incontinence in the United States: a systematic review. J Manag Care Pharm. 2014;20:130-140.
  4. Zhu Y, Zhu Z, Chen J. Risk factors associated with the progression of overactive bladder among patients with type 2 diabetes. Int J Clin Pract. 2019;e:13395
  5. Liu RT, Chung MS, Lee WC, et al. Prevalence of overactive bladder and associated risk factors in 1359 patients with type 2 diabetes. Urology. 2011;78:1040-1045.
  6. Ikeda M, Nozawa K. Prevalence of overactive bladder and its related factors in Japanese patients with diabetes mellitus. Endocr J. 2015; 62: 847-854.
  7. Palleschi G, Pastore AL, Maggioni C, et al. Overactive bladder in diabetes mellitus patients: a questionnaire-based observational investigation. World J Urol. 2014;32:1021-1025.
  8. Chiu AF, Huang MH, Wang CC, Kuo HC.  Higher glycosylated hemoglobin levels increase the risk of overactive bladder syndrome in patients with type 2 diabetes mellitus. Int J Urol. 2012; 19: 995-1001.
  9. Liu RT, Chung MS, Chuang YC, et al.  The presence of overactive bladder wet increased the risk and severity of erectile dysfunction in men with type 2 diabetes. J Sex Med. 2012;9:1913-1922.
  10. Kebapci N, Yenilmez A, Efe B, et al. Bladder dysfunction in type 2 diabetic patients. Neurourol Urodyn. 2007; 26: 814-819. 
  11. Kaplan SA, Te AE, Blaivas JG. Urodynamic findings in patients with diabetic cystopathy.  J Urol 1995;153:342-344.
  12. Changxiao H, Zhengyong Y, Shibing Y, et al.  Clinical and urodynamic evaluation of women referred with diabetes mellitus. Int Urogynecol J. 2014;25:979-983.
  13. Daneshgari F, Moy ML. Current indications for neuromodulation. Urol Clin North Am. 2005;32: 37-40.
  14. Golbidi S, Laher I. Bladder dysfunction in diabetes mellitus.  Front Pharmacol. 2010;1:136.
  15. Fuselier A, Hanberry J, Margaret Lovin J, Gomelsky A.  Obesity and Stress Urinary Incontinence: Impact on Pathophysiology and Treatment.  Curr Urol Rep. 2018;19:10.
  16. de Boer TA, Slieker-ten Hove MC, Burger CW, Vierhout ME.  The prevalence and risk factors of overactive bladder symptoms and its relation to pelvic organ prolapse symptoms in a general female population. Int Urogynecol J. 2011;22(5):569-575.
  17. Link CL, Steers WD, Kusek JW, McKinlay JB. The association of adiposity and overactive bladder appears to differ by gender: results from the Boston Area Community Health survey.  J Urol. 2011;185:955-963.
  18. Teleman PM, Lidfeldt J, Nerbrand C, et al, for the WHILA study group. Overactive bladder: prevalence, risk factors and relation to stress incontinence in middle-aged women. BJOG. 2004;111:600-604.
  19. McGrother CW, Donaldson MM, Hayward T, et al; Leicestershire MRC Incontinence Study Team.  Urinary storage symptoms and comorbidities: a prospective population cohort study in middle-aged and older women.  Age Ageing. 2006;35:16-24.
  20. Uzun H, Zorba OÜ.  Metabolic syndrome in female patients with overactive bladder.  Urology 2012; 79: 72-75.
  21. Subak LL, King WC, Belle SH, et al.  Urinary incontinence before and after bariatric surgery.  JAMA Intern Med 2015; 175: 1378-1387.
  22. Lai HH, Helmuth ME, Smith AR, et al. Relationship Between Central Obesity, General Obesity, Overactive Bladder Syndrome and Urinary Incontinence Among Male and Female Patients Seeking Care for Their Lower Urinary Tract Symptoms. Urology. 2019;123:34-43.
  23. Bunn F, Kirby M, Pinkney E, et al.  Is there a link between overactive bladder and the metabolic syndrome in women? A systematic review of observational studies.  Int J Clin Pract 2015; 69: 199-217.
  24. Gormley EA, Lightner DJ, Burgio KL, et al; American Urological Association; Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction.  Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline.  J Urol 2012; 188(6 Suppl): 2455-2463.
  25. Lightner DJ, Gomelsky A, Souter L, Vasavada SP.  Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults: AUA/SUFU Guideline Amendment 2019. J Urol. 2019; 202: 558-563.
  26. Staskin D, Herschorn S, Fialkov J, Tu LM, Walsh T, Schermer CR. A prospective, double-blind, randomized, two-period crossover, multicenter study to evaluate tolerability and patient preference between mirabegron and tolterodine in patients with overactive bladder (PREFER study). Int Urogynecol J. 2018;29(2):273-283.
  27. Gratzke C, van Maanen R, Chapple C, et al. Long-term Safety and Efficacy of Mirabegron and Solifenacin in Combination Compared with Monotherapy in Patients with Overactive Bladder: A Randomised, Multicentre Phase 3 Study (SYNERGY II). Eur Urol. 2018;74(4):501-509.
  28. Herschorn S, Staskin D, Tu LM, et al. Patient-reported outcomes in patients with overactive bladder treated with mirabegron and tolterodine in a prospective, double-blind, randomized, two-period crossover, multicenter study (PREFER). Health Qual Life Outcomes. 2018;16(1):69.

 

First Article:
Interrelationship between Overactive Bladder and Type 2 Diabetes
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