Diabetic Cystopathy Occurs Independently from Other Atherosclerotic Risks.

It has not yet been clarified whether atherosclerotic risks other than diabetes are related to bladder small fiber neuropathy (cystopathy) in type 2 diabetes. The aim of this study was to answer this question by urodynamics. This was a retrospective study. The subjects were 44 patients: 27 male, 17 female; mean age 67.0 ± 12.7 years; mean duration of diabetes 16.8 ± 13.1 years; mean HbA1c 7.8 ± 1.2%. We analyzed the relationship between diabetic cystopathy (at least one of the following abnormalities in urodynamics: decreased bladder sensation, post-void residual, detrusor overactivity, low-compliance detrusor) and clinical items, i.e., severity and duration of diabetes, nerve conduction, body mass index, blood pressure, cardio-ankle vascular stiffness index, and ultrasound Doppler echography (plaque score, intima-media thickness) in these patients. As a result, urodynamic diabetic cystopathy was not correlated with any of the above systemic items. In conclusion, the above findings suggest that bladder small fiber neuropathy can occur independently from systemic atherosclerotic risks.

Introduction

Type 2 diabetes is known to cause bladder small fiber neuropathy (also called cystopathy) [1], with symptoms ranging from loss of bladder sensation to post-void residual [2, 3]. In contrast, it has not been clarified whether systemic atherosclerotic risks other than diabetes are related to diabetic cystopathy. The goal of this study was to address this question by urodynamics as the objective bladder measure.

Subjects and Methods

This was a retrospective study. Subjects were 44 type 2 diabetes [4] patients referred to our institution because of their lower urinary tract symptoms. All subjects were evaluated in our outpatient clinic: 27 male, 17 female; mean age 67.0 ± 12.7 years; mean duration of diabetes 16.8 ± 13.1 years; mean HbA1c 7.8 ± 1.2%. Most were receiving treatment, such as oral sulfonylurea, thiazolidine derivatives, dipeptidyl peptidase-4 inhibitors, or insulin. All patients were able to walk independently.

In these patients we analyzed the relationship between diabetic cystopathy (at least one of the following objective abnormalities in urodynamics: decreased bladder sensation [first sensation > 300 mL or bladder capacity > 600 mL], detrusor overactivity, low-compliance detrusor [storage phase items], detrusor underactivity, and post-void residual [> 50 mL, voiding phase item]) with systemic factors, such as severity and duration of diabetes, nerve conduction abnormality (defined as Dyck's criteria ≥7, i.e., a total of five nerve conduction abnormalities [5]), body mass index, blood pressure, cardio-ankle vascular stiffness index, and Doppler echography (plaque score, intima-media thickness). Patients with comorbid diseases/conditions such as prostatic hyperplasia (ultrasound-measured volume > 30 mL), urological/psychiatric drugs, alcoholism, uremia, or amyloidosis that might cause limb neuropathy/lower urinary tract dysfunction (LUTD) were excluded.

The test methods for determining LUTD (using equipment from Urovision and Life-Tech Inc., Houston, TX, USA) were according to the International Continence Society standards. They included ultrasound echography of the prostate gland in all men (men with a prostate volume > 20 mL were excluded), a nerve conduction study (Neuropack M2; Nihon Kohden Inc., Tokyo, Japan), a cardio-ankle vascular stiffness index test [6] (pulse wave velocity-derived parameter) using a VaSera instrument (Fukuda Denshi Inc., Tokyo, Japan), and an ultrasound Doppler echography (SSA-260A; Toshiba, Inc, Tokyo, Japan). Data were analyzed by Student's t test and Mann-Whitney U test.

Results

Our results indicated that there were no significant correlations between objective urodynamic diabetic cystopathy and any of the above systemic factors (Table 1). We also performed two validated questionnaires − the overactive bladder symptom score (storage symptoms) and the international prostate symptom score (mainly voiding symptoms) − and there was no relationship between atherosclerotic factors either (data not shown).

Table 1

Relationship between urodynamic LUTD and clinical risk factors in diabetes

	Urodynamic LUTH −	Urodynamic LUTD +	p value
Age, years	67.9±10.7	66.4±13.6	ns
Duration of diabetes, years	17.9±15.3	16.3±11.9	ns
HbA1c, %	7.7±0.9	8±1.5	ns
Blood glucose, mg/dL	201.3±91.2	192.6±93	ns
Large fiber neuropathy (by nerve conduction study of the extremities), %	71.4	86.7	ns
Obesity (body mass index), %1	23.4±4.1	22.7±4.5	ns
Systolic blood pressure, mm Hg1	141.6±24.2	148.4±29.3	ns
Diastolic blood pressure, mm Hg1	77.2±11.6	90±19.7	ns
Cardio-ankle vascular stiffness index1	9.6±1.0	9.8±1.2	ns
Carotid Doppler echography (plaque score)1	7.9±5.7	9±5.4	ns
Carotid Doppler echography (intima-media thickness), mm1	0.9±0.24	0.8±0.2	ns

LUTD, lower urinary tract dysfunction.

Atherosclerotic risks other than diabetes.

Discussion

It is possible that a close relationship between LUTD and a systemic condition might contribute to the pathogenesis, prognosis, and management of diabetic cystopathy. To our knowledge, no study has assessed whether urodynamic diabetic cystopathy is correlated with atherosclerotic risks other than diabetes itself. Previous studies have suggested a relationship between diabetic cystopathy and the severity [7] and time course [3] of type 2 diabetes. Diabetic cystopathy in type 2 diabetes, which is mainly autonomic small-diameter myelinated/unmyelinated fiber neuropathy, has been said to occur together with large-diameter myelinated fiber limb neuropathy [8]. On the other hand, it has also been suggested that diabetic cystopathy occurs independently from limb neuropathy [9]. The exact reason for this discrepancy is unknown. However, Dyck et al. [10] reported that diabetic limb polyneuropathy most commonly represents metabolic derangements that are secondary to chronic hyperglycemia such as polyol shunting, accumulation of advanced glycation end products, oxidative stress, and lipid abnormalities. Microvascular alterations with mild mechanical trauma, inflammation, microvasculitis, and ischemia are also causative factors [10]. In contrast, molecular changes in autonomic small-diameter myelinated/unmyelinated fiber in type 2 diabetes remain to be clarified [11, 12] and may have different pathophysiology from limb neuropathy.

The limitations of this study include the relatively small number of patients and the fact that it was a retrospective study following a single cohort. Nevertheless, our results contribute to the information regarding the care of patients with diabetic cystopathy, which affects quality of life in patients. Future prospective studies of a large cohort to further observe the relationship are warranted.

In conclusion, the present study results show that urodynamic diabetic cystopathy is not significantly correlated with atherosclerotic risks, suggesting that diabetic cystopathy can occur independently from systemic atherosclerotic risks.

Statement of Ethics

The present research complied with the guidelines for human studies, and the research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. All the patients gave their written informed consent. The present research was approved by the Ethics Committee of Sakura Medical Center, Toho University (2011-059).

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

The authors have no funding sources to declare.

Author Contributions

A. Shimizu: acquisition, analysis, and interpretation of data. R. Sakakibara: study concept and design, acquisition of subjects and/or data, analysis and interpretation of data, and manuscript preparation. O. Takahashi: acquisition, analysis, and interpretation of data. F. Tateno and Y. Aiba: acquisition of subjects and/or data.