Diabetic Cystopathy

Definitions / Terminology:

Diabetic Cystopathy is traditionally described as a triad of decreased sensation, increased capacity and poor emptying; however it has become increasingly evident that diabetic patients have significant bother from overactive bladder (OAB)

Historical background:

Whilst the prevalence of type 1 DM seems unchanged, there is a continuing rise in prevalence of type 2 DM, mostly related to life style change and obesity rates [1, 2]. Lower urinary tract (LUT) complications are among the most common complications of DM. The most common, bothersome LUT complication of DM is diabetic cystopathy (DC)[3]. DC is considered a part of the spectrum of autonomic disturbances associated with DM that include gastroesophageal hypotonia, hyperhydrosis, erectile dysfunction, and autonomous cardiac abnormalities [4]. Diabetic patients suffer from various polyneuropathies, with ‘diabetic cystopathy’ reported in 43-87 % of insulin-dependent diabetics without gender or age differences. It is also described in about 25% of type 2 diabetic patients, which clinically manifests as decreased bladder sensation, increased residual urine, and detrusor overactivity (DO) [5]. Frimodt- Moller was the first to introduce the term “diabetic cystopathy” with the meaning of “involvement of the lower urinary tract by diabetic neuropathy”, that causes paralysis of the detrusor muscle leading to voiding difficulties [6].

Epidemiology:

Diabetes mellitus (DM) affects 8.3 % of the U.S. population. Although DM has reached epidemic proportions all over the world; bladder dysfunction has not been assessed until now in epidemiological and longitudinal studies or randomized controlled (RCTs).

Pathogenesis:

The pathophysiology of DC has been found to be multifactorial, with neuronal, urothelial and smoothmuscle dysfunction. In DC, patients develop impairment in bladder sensation, increased residual urine, and DO. The proposed hypotheses for the peripheral nerve damage seen in diabetic patients include the altered metabolism of glucose, ischemia, superoxide-induced free-radical formation, and impaired axonal transport [7]. The decrease in nerve growth factor (NGF) levels was associated with increased bladder capacity and post-void residual. NGF in the bladder supports the survival and maintenance of peripheral sensory and autonomic neurons, it also promotes the regeneration of damaged peripheral neurons [8, 9]. However diabetic cerebral vasculopathy and, to a lesser extent, peripheral nerve irritation can be the cause for DO and increased bladder sensation in diabetic patients[10]

History / Symptoms/ Signs:

DC is traditionally described as a triad of decreased sensation,increased capacity and poor emptying; however it has become increasingly evident that diabetic patients have significant bother from overactive bladder (OAB). In a dedicated diabetic center, in which all patients were screened, 22.5 % had OAB and 48.0 % of those with OAB had incontinence [11]. A urological study in elderly diabetic patients reported that only 17 % presented with urinary retention, while 76 % had involuntary bladder contractions presenting as urgency and/or nocturia [12]. Diabetes significantly altered voiding patterns in a significant proportion of women treated at the diabetic clinic [13].

Investigations

Biochemical tests: for assessment of diabetic control and screening for end organ damage, including serum glucose, glycosylated haemoglobin, urea and creatinine to assess renal function should be obtained. Since diabetic women are at increased risk of bacterial cystitis, microscopic urinalysis and culture are essential in assessing patients complaining of LUTS.

Urodynamics: The prevalence of urodynamic abnormalities have been reported as high as 75–100 %, even in absence of LUTS, especially in the presence of peripheral neuropathy [14]. Measurement of peak urinary flow rate and post void residual (PVR) should be considered in diabetic patients with LUTS by portable ultrasound [15]. Based on the results from several studies, DO is the most predominant urodynamic finding in patients with DM. A review by Kaplan et al. of urodynamic findings in 182 diabetes cases showed that detrusor over activity was the most common urodynamic observation (48 %), followed by impaired detrusor contractility (30 %), whilst 15 % had poor compliance [16].

Conservative Management

Patients who suffer from reduced bladder sensation with infrequent voiding should be advised about timed and double voiding on a consistent and regular schedule. In cases of significant impairment of detrusor contractility with impaired voiding, intermittent catheterization (IC) is necessary to achieve bladder emptying and reduce the risk of urinary tract infection with potential deterioration of renal function. Long term antimicrobial prophylaxis may be required for recurrent urinary tract infection [17].

Medical and Surgical Treatment Antimuscarinic agents represent the cornerstone of treatment for patients who presents with OAB. Few surgical options are available to treat DC. It has been shown that sacral neuromodulation is as effective in diabetic versus nondiabetic patients; however diabetic patients have increased risk of device explantation secondary to infection [18]. A worldwide clinical trial reported 71 % improvement in urinary retention after 5 year follow-up in diabetic patients [19].

References :

1. Boyle JP, Honeycutt AA, Narayan KM, et al. Projection of DM burden through 2050: impact of changing demography and disease prevalence in the U.S. DMCare. 2001;24:1936–40.

2. Amos AF, McCarty DJ, Zimmet P. The rising global burden of DM and its complications: estimates and projections to the year 2010.

Diabet Med. 1997;14:S1–85.

3. Urologic Complications of Diabetes Mellitus. Bethesda: National

Institute of Diabetes and Digestive and Kidney Diseases, Bladder

Research Progress Review Group 2002; p 133.

4. Niakan E, Harati Y, Comstock JP. Diabetic autonomic neuropathy.

Metabolism. 1986;35:224–34.

5. Bradley WE. Diagnosis of urinary bladder dysfunction in diabetes mellitus. Ann Intern Med. 1980;92:323–6.

6. Frimodt-Moller C. Diabetic cystopathy. A review of the urodynamic and clinical features of neurogenic bladder dysfunction in DM mellitus. Dan Med Bull. 1978;25:49–60.

7.Apfel SC. Neurotrophic factors and diabetic peripheral neuropathy.

Eur Neurol. 1999;41 Suppl 1:27.

8.Pittenger G, Vinik A. Nerve growth factor and diabetic neuropathy. Exp Diabesity Res. 2003;4(4):271–85.

9. Li Y, Shi B, Wang D, Wang P, Laudon V, Liu Y, et al. Nerve growth factor and substance P: expression in a rat model of diabetic bladder. Int Urol Nephrol. 2011;43:109–16.

10. Yamaguchi C, Sakakibara R, Uchiyama T, Uchiyama T, Yamamoto

T, Ito T, et al. Overactive bladder in diabetes: a peripheral or central mechanism? Neurourol Urodyn. 2007;26:807–13.

11. Liu RT, Chung MS, Lee WC, Chang SW, Huang ST, Yang KD, et al. Prevalence of overactive bladder and associated risk factors in

1359 patients with type 2 diabetes urology. Nov. 2011;78:1040–5.

12. Starer P, Libow L. Cystometric evaluation of bladder dysfunction in elderly diabetic patients. Arch Intern Med. 1990;150:810–3.

13. Lee WC, Wu HP, Tai TY, et al. Effects of diabetes on female voiding behavior. J Urol. 2004;172:989–92.

14.Buck AC, Reed PI, Siddiq YK, et al. Bladder dysfunction and neuropathy in diabetes. Diabetologia. 1976;12:251–8.

15. Hunter KF, Moore KN. DM-associated bladder dysfunction in the older adult(CE). Geriatric Nursing (New York, NY).

2003;24:138–45.

16. Kaplan SA, Te AE, Blaivas JG. Urodynamic findings in patients with diabetic cystopathy. J Urol. 1995;153:342–4.

17. Hill SR, Fayyad AM, Jones GR. Diabetes mellitus and female lower urinary tract symptoms: a review. Neurourol Urodyn.

2008;27:362–7.

18. Daniels DH, Powell CR, Braasch MR, et al. Sacral neuromodulation in diabetic paients: success and complications in the treatment of voiding dysfunction. Neurourol Urodyn. 2010;29:578. This should be required reading for any urologist treating voiding dysfunction.

19. Van Kerrebroeck PE, Van Voskuilen AC, Heesakkers JP, et al.

Results of sacral neuromodulation therapy for urinary voiding dysfunction: outcomes of a prospective, worldwide clinical study.

J Urol. 2007;178:2029–34.