Investigation of urodynamic characteristics and bladder sensory function in the early stages of diabetic bladder dysfunction in women with type 2 diabetes.

PURPOSE: We studied urodynamic characteristics and bladder sensory function in the early stages of diabetic bladder dysfunction in diabetic women. MATERIALS AND METHODS: A total of 86 consecutive type 2 diabetic women with minimal confounders of voiding dysfunction followed at a diabetes clinic were prospectively enrolled and subjected to urodynamic studies. The sensory response of Adelta and C fibers of the bladder was measured by intravesical current perception threshold testing at frequencies of 250 and 5 Hz, respectively. RESULTS: Of these 86 women 30 (34.9%) were classified as having detrusor underactivity, 12 (14.0%) presented signs of detrusor overactivity, 11 (12.8%) were referred to as having bladder outlet obstruction and 33 (38.4%) showed normal detrusor function on urodynamics. The normal detrusor function group was the reference group. The detrusor underactivity group showed impaired emptying function and decreased sensation on cystometry and intravesical current perception threshold testing. The detrusor overactivity group showed impaired storage and emptying function but had no significant changes in intravesical current perception threshold values. When the normal detrusor function group and detrusor underactivity group were pooled to perform multivariate analysis, an increase in current perception threshold values was associated with a decrease in bladder voiding efficiency on 5 and 250 Hz current perception threshold testing. CONCLUSIONS: Our data provide the electrophysiological evidence that indicates an association between impaired Adelta as well as C fiber bladder afferent pathways and poor emptying function in diabetic women with detrusor underactivity. Diabetes can affect the bladder presumably via peripheral pathogenetic mechanisms to induce detrusor overactivity with impaired contractility.

Efficacy and tolerability of acarbose in Asian patients with type 2 diabetes inadequately controlled with diet and sulfonylureas.

The objective of this study was to investigate the efficacy, tolerability, and safety of acarbose in the improvement of glycemic control in Asian patients with type 2 diabetes inadequately controlled by diet and sulfonylureas. A 24-week, double-blind, placebo-controlled multicenter group comparison study was conducted. Patients were randomized to receive acarbose titrated up to 100-mg tid (n=36) or matching placebo (n=33). Concomitant sulfonylurea treatment remained unchanged throughout the study. The primary efficacy parameter was the change in HbA(1c) from baseline to double-blind endpoint. Secondary efficacy variables consisted of the change from baseline to endpoint in blood glucose (fasting and 1-h postprandial), serum insulin (fasting and 1-h postprandial), and urinary glucose. In the intention-to-treat (ITT) analysis, acarbose treatment was associated with significantly greater reductions in glycated hemoglobin (HbA(1c)) (-0.91% vs. placebo 0.13%, P=.0018) and 1-h postprandial blood glucose levels (-2.84 mmol/l vs. placebo -0.28 mmol/l, P=.002) compared to placebo. There were no significant differences between the treatment groups regarding changes in fasting blood glucose, fasting or 1-h postprandial serum insulin, urinary glucose, or body weight. Adverse events occurred with similar frequency in both treatment arms except for drug-related gastrointestinal side-effects associated with acarbose (acarbose 48.5% and placebo 12.5%). This study has shown that the use of acarbose in Asian patients with type 2 diabetes inadequately controlled by diet and sulfonylureas is efficacious in improving metabolic control and that acarbose is safe and well tolerated.

Hyposensitivity of C-fiber afferents at the distal extremities as an indicator of early stages diabetic bladder dysfunction in type 2 diabetic women.

PURPOSE: To investigate the relationship between distal symmetric peripheral neuropathy and early stages of autonomic bladder dysfunction in type 2 diabetic women. MATERIALS AND METHODS: A total of 137 diabetic women with minimal coexisting confounders of voiding dysfunction followed at a diabetes clinic were subject to the following evaluations: current perception threshold (CPT) tests on myelinated and unmyelinated nerves at the big toe for peroneal nerve and middle finger for median nerve, uroflowmetry, post-void residual urine volume, and overactive bladder (OAB) symptom score questionnaire. Patients presenting with voiding difficulty also underwent urodynamic studies and intravesical CPT tests. RESULTS: Based on the OAB symptom score and urodynamic studies, 19% of diabetic women had the OAB syndrome while 24.8% had unrecognized urodynamic bladder dysfunction (UBD). The OAB group had a significantly greater mean 5 Hz CPT test value at the big toe by comparison to those without OAB. When compared to diabetic women without UBD, those with UBD showed greater mean 5 Hz CPT test values at the middle finger and big toe. The diabetic women categorized as C-fiber hyposensitivity at the middle finger or big toe by using CPT test also had higher odds ratios of UBD. Among diabetic women with UBD, the 5 Hz CPT test values at the big toe and middle finger were significantly associated with intravesical 5 Hz CPT test values. CONCLUSIONS: Using electrophysiological evidence, our study revealed that hyposensitivity of unmyelinated C fiber afferents at the distal extremities is an indicator of early stages diabetic bladder dysfunction in type 2 diabetic women. The C fiber dysfunction at the distal extremities seems concurrent with vesical C-fiber neuropathy and may be a sentinel for developing early diabetic bladder dysfunction among female patients.

Metabolic syndrome components worsen lower urinary tract symptoms in women with type 2 diabetes.

CONTEXT: Diabetic women are more susceptible to develop lower urinary tract symptoms (LUTS), especially overactive bladder (OAB). However, data regarding the effect of components of metabolic syndrome (MS) on this association are conflicting. OBJECTIVE: The objective of the study was to examine the potential role of MS in the development of LUTS in diabetic women. DESIGN: The study was a prevalence study conducted between 2005 and 2007. SETTING: The study was conducted in a university hospital. PARTICIPANTS: A total of 518 women with type 2 diabetes aged 50-75 yr were included. They were subgrouped as MS (47.5%) and non-MS (52.5%) groups according to whether they fulfilled the criteria of MS. MAIN OUTCOME MEASURE: We used American Urological Association Symptom Index (AUA-SI) to evaluate LUTS and Indevus Urgency Severity Scale to evaluate OAB, respectively. RESULTS: Women in the MS group had significantly higher storage and total AUA-SI scores as well as a higher prevalence of LUTS and OAB. Most intriguingly, the number of MS components was strongly associated with the LUTS severity because the AUA-SI scores increased in parallel to the number of components were present. Similar results were found between MS and OAB. Multivariate analysis revealed that peripheral neuropathy, but not MS, significantly predicted LUTS in diabetic women after age adjustment. However, MS remained significantly predictive for LUTS and OAB after additional adjustment for neuropathy. CONCLUSIONS: Our results suggest that MS may especially influence LUTS and OAB in diabetic women, probably by compounding the effect of peripheral neuropathy.

Lower urinary tract symptoms and uroflowmetry in women with type 2 diabetes mellitus with and without bladder dysfunction.

OBJECTIVES: To study the presence of lower urinary tract symptoms and parameters of uroflowmetry in women with type 2 diabetes mellitus with and without bladder dysfunction versus healthy controls. METHODS: After eliminating the possible confounders that might cause bladder dysfunction, 182 female patients at a diabetic clinic were evaluated by the American Urological Association Symptom Index (AUA-SI) questionnaire and uroflowmetry with postvoid residual (PVR) urine volume estimate. Their data were compared with the data from 197 healthy women, frequency-matched by age. RESULTS: Using a cutoff value of bladder voiding efficiency of less than 75% with a PVR greater than 50 mL but less than 100 mL, a PVR greater than 100 mL, or a total volume greater than 500 mL, 47 patients (25.8%) were stratified as having bladder dysfunction. These patients had a significantly greater mean AUA-SI score (mean +/- standard error of the mean 9.6 +/- 0.8, P <0.001), as well as a lower maximum uroflow value (15.2 +/- 1.2 mL/s, P <0.001) compared with the control groups. The odds ratio of each lower urinary tract symptom was significantly greater in this group, except for straining (P = 0.12). A high proportion with an intermittent uroflow pattern (odds ratio 4.42, P <0.001) was also noted. Compared with the healthy controls, the diabetic women had no bladder dysfunction and seemed unaffected by the lower urinary tract symptoms as defined by the AUA-SI scoring system, with the exception of nocturia (odds ratio 2.62, P = 0.006). CONCLUSIONS: Women with diabetes may have an increased risk of nocturia even without bladder dysfunction. A high AUA-SI score and lower maximum uroflow are likely to be good markers for diabetic bladder dysfunction.

Effects of diabetes on female voiding behavior.

PURPOSE: We studied voiding behavior in women with type 2 diabetes vs nondiabetic female controls and examined factors associated with voiding dysfunction in patients with diabetes. MATERIALS AND METHODS: After eliminating coexisting medical factors that could affect voiding function we evaluated voiding behaviors in 194 female patients with diabetes treated regularly at a diabetic clinic and 162 control women using a lower urinary tract symptom questionnaire based mainly on the American Urological Association Symptom Index questionnaire and free flow analyses with post-void residual urine estimates. Emptying efficiency was defined as 100% x volume voided/(volume voided + post-void residual urine). RESULTS: Compared with controls patients with diabetes had significantly higher nocturia scores (p = 0.003), weaker urinary streams (p = 0.02), less voided volumes (220 +/- 97 vs 280 +/- 104 ml, p = 0.04) and lower maximal flow rates (19.4 +/- 8.4 vs 25.9 +/- 8.5 ml per second, p <0.001). Remarkable residual urine (100 ml or greater) was detected in 1.8% of controls vs 13.9% of patients. After controlling for age and voided volume diabetes was significantly associated with a decrease in baseline maximum flow of 4.5 ml per second (95% CI 2.9 to 6.2). In patients with diabetes peripheral neuropathy was an independent factor associated with the decrease in emptying efficiency (p = 0.03). CONCLUSIONS: Diabetes significantly altered voiding patterns in a significant proportion of women treated at the diabetic clinic. Peripheral neuropathy is an important factor associated with diabetic voiding dysfunction.

Skin denervation in type 2 diabetes: correlations with diabetic duration and functional impairments.

Sensory neuropathy is a prominent component of diabetic neuropathy. It is not entirely clear how diabetes influences skin innervation, and whether these changes are correlated with clinical signs and laboratory findings. To investigate these issues, we performed skin biopsies on the distal leg of 38 consecutive type 2 diabetic patients with sensory symptoms in lower limbs (25 males and 13 females, aged 56.2 +/- 9.4 years) and analysed the correlations of intraepidermal nerve fibre (IENF) densities in skin with glycaemic status (duration of diabetes, HbA1C, and fasting and post-prandial glucose levels), and functional parameters of small fibres (warm and cold thresholds) and large fibres (vibratory threshold and parameters of nerve conduction studies). Clinically, 23 patients (60.5%) had signs of small-fibre impairment, and 19 patients (50.0%) had signs of large-fibre impairment. IENF densities were much lower in diabetic patients than in age- and gender-matched controls (1.794 +/- 2.120 versus 9.359 +/- 3.466 fibres/mm, P < 0.0001), and 81.6% (31/38) of diabetic patients had reduced IENF densities. IENF densities were negatively associated with the duration of diabetes (standardized coefficient: -0.422, P = 0.015) by analysis with a multivariate linear regression model. Abnormal results of functional examinations were present in 81.6% (warm threshold), 57.9% (cold threshold), 63.2% (vibratory threshold) and 49% (amplitude of sural sensory action potential) of diabetic patients. Among the three sensory thresholds, the warm threshold temperature had the highest correlation with IENF densities (standardized coefficient: -0.773, P < 0.0001). On nerve conduction studies in lower-limb nerves, there were abnormal responses in 54.1% of sural nerves, and 50.0% of peroneal nerves. Of neurophysiological parameters, the amplitude of the sural sensory action potential had the highest correlation with IENF density (standardized coefficient: 0.739, P < 0.0001). On clinical examination, 15 patients showed no sign of small-fibre impairment, but seven of these patients had reduced IENF densities. In conclusion, small-fibre sensory neuropathy presenting with reduced IENF densities and correlated elevation of warm thresholds is a major manifestation of type 2 diabetes. In addition, the extent of skin denervation increases with diabetic duration.