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Prevalence of Overactive Bladder and Associated Risk Factors in 1359 Patients With Type 2 Diabetes
Female Urology Prevalence of Overactive Bladder and Associated Risk Factors in 1359 Patients With Type 2 Diabetes Rue-Tsuan Liu, Min-Shen Chung, Wei-Chia Lee, Sueh-Wen Chang, Siang-Ting Huang, Kuender D. Yang, Michael B. Chancellor, and Yao-Chi Chuang OBJECTIVE METHODS
RESULTS
CONCLUSION
To evaluate overactive bladder (OAB, dry and wet) and the associated risk factors of OAB wet (with incontinence) in type 2 diabetes. A self-administered questionnaire containing the OAB symptom score (OABSS, 0-15, with higher numbers indicating an increasing severity of symptoms) was obtained from subjects with type 2 diabetes at a dedicated diabetic center. The association of age, sex, duration of diabetes, body mass index, waist circumference, glycated hemoglobin level, high-sensitive C-reactive protein level, and diabetes-associated complications to the risk of OAB and OAB wet was evaluated. Of 1359 consecutive subjects, 22.5% reported having OAB, with 11.7% reporting OAB dry and 10.8% OAB wet. The difference in symptom severity was statistically significant among those without OAB and those with OAB dry and OAB wet (OABSS 2.5 ⫾ 1.4, 5.9 ⫾ 1.6, and 8.9 ⫾ 2.6, respectively). The prevalence of OAB and OAB wet was 2.4-fold and 4.2-fold greater, respectively, in patients with a diabetes duration ⬎10 years and age ⬎50 years. Age and male sex and age and waist circumference were independent risk factors for OAB and OAB wet, respectively, after multivariate analysis. Glycated hemoglobin and high-sensitivity C-reactive protein levels were similar between patients with diabetes patients with and without OAB. In the dedicated diabetic center in which all patients were screened, 22.5% had OAB, and 48.0% of those with OAB had incontinence. These findings can help guide the collaboration between urologists and diabetologists to work toward developing screening for, and early treatment of, urologic complications in higher risk patients. UROLOGY 78: 1040 –1045, 2011. © 2011 Elsevier Inc.
D
iabetes mellitus (DM), a chronic metabolic condition, is an increasing health concern across the world with significant medical and health economic issues. According to the International Diabetes Federation, the North American Region has a DM prevalence of 7.9% in the adult population.1 Using Taiwan National Health Insurance claims data, Chang et al2 reported that the prevalence of type 2 DM among those aged ⬎20 years was 6.8% in Taiwan. Studies have shown that overactive bladder (OAB) syndrome, defined as urgency (complaint of a sudden compelling desire to pass urine that is difficult to defer), with or without inconti-
Funding Support: This study was supported by grant CMRPG 860381. From the Divisions of Metabolism; and Urology and Department of Medical Research, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; and Department of Urology, William Beaumont Hospital, Royal Oak, Michigan Reprint requests: Yao-Chi Chuang, M.D., Division of Urology, Department of Surgery Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung, 123 Ta Pei Road, Niao-Sung, Hsiang, Kaohsiung Hsien, Taiwan. E-mail: [email protected] Submitted: April 2, 2011, accepted (with revisions): May 13, 2011
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© 2011 Elsevier Inc. All Rights Reserved
nence, usually with urinary frequency and nocturia,3 commonly occurs in patients with DM and have a significant effect on society.4,5 A survey of 3962 women demonstrated that OAB affects 21.4% of diabetic women compared to only 12.5% of nondiabetic women.6 However, the overall prevalence of OAB in diabetic patients, including the male population, has rarely been reported. Diabetologists and urologists practice in different fields and often treat OAB and DM as separate entities without correlation. Furthermore, the presence of OAB wet (incontinence) has a stronger effect on quality of life than OAB dry (no incontinence). It would be important to assess all diabetic patients for the presence or absence of OAB symptoms, especially with incontinence, and help determine who would be at risk and who should be screened. DM is associated with systemic inflammation, neuropathy, cardiovascular complications, and metabolic syndrome, all of which have been linked to OAB.7,8 To more clearly understand the association between OAB and DM, we conduct a cross-sectional study to examine the relationship between OAB and markers of DM, in0090-4295/11/$36.00 doi:10.1016/j.urology.2011.05.017
cluding microvascular complications of DM (eg, retinopathy, neuropathy, and nephropathy), macrovascular complications (eg, coronary artery disease and stroke), diabetic control (glycated hemoglobin [HbA1c]), inflammatory condition (high-sensitivity C-reactive protein [hs-CRP]), obesity (eg, waist circumference, body mass index), and metabolic syndrome.
MATERIAL AND METHODS Patient Enrollment A cross-sectional study was conducted among 1715 consecutive diabetic patients attending a single outpatient diabetic clinic managed by 1 diabetologist (R.T.L.) at Chang Gung Memorial Hospital-Kaohsiung Medical Center from April 2008 to November 2008. The study only included subjects who had already been enrolled in the diabetic clinic for ⬎1 year. Of all the patients, 46 were diagnosed with type 1 DM and were excluded from the present study. Of the patients, 1359 agreed to complete the self-administered questionnaires composed of demographic data and a validated Chinese version of the OAB symptom score (OABSS). Diabetic patients with new-onset neurologic disorders (eg, stroke, Parkinsonism, spinal cord injury, and multiple sclerosis), active urinary tract infections, previous major pelvic surgery, or evidence of pelvic organ prolapse were excluded from the present study. The institutional review board approved the study protocol, and all participants gave their written informed consent.
Assessment for OAB OABSS, a 4-item questionnaire developed by Homma et al,9 was used to assess the symptoms of OAB. The OABSS total score is a sum of the 4 item scores from a self-administered questionnaire of 4 symptoms: daytime frequency (score 0-2), nighttime frequency (score 0-3), urgency (score 0-5), and urgency incontinence (score 0-5). In the present study, the patients with an urgency score of ⱖ2 and sum score of ⱖ3 were considered to have OAB. Of the patients with OAB, those with an urgency incontinence score of ⱖ2 (once a week or more) were considered to have OAB wet. The sum score (0-15, with greater numbers indicating increasing severity of symptoms) was categorized as none (score 0-2), mild (score 3-5), moderate (score 6-11), or severe (score ⱖ12) OAB.9 The OABSS has been validated and adapted linguistically and psychometrically for their Chinese counterparts in Taiwan by Taiwanese Continence Society.10
Clinical Profiles and Definition Each patient participated in a detailed interview regarding their personal disease, smoking, and drinking history by 2 trained interviewers. The parameters evaluated were age, duration of DM, microvascular complications of DM (ie, retinopathy, neuropathy, and nephropathy), macrovascular complications of DM (ie, coronary artery disease and stroke), diabetic control, inflammatory condition (hs-CRP), body mass index (calculated as the body weight in kilograms divided by the square of the body height in meters), waist circumference, metabolic syndrome, and biochemical data, including total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, uric acid, serum creatinine, HbA1c, hsCRP, complete blood count, and differential count. UROLOGY 78 (5), 2011
The estimated glomerular filtration rate was calculated using the modified Diet and Renal Disease equation. The urinary albumin concentration was measured by random daytime urine samples. Albumin excretion rate was defined entirely by calculation of the albumin/creatinine ratio in urine specimen. The definition of normal albuminuria, microalbuminuria, and macroalbuminuria was an albumin/creatinine ratio ⬍0.03 mg/mg once in one collected urine sample, 0.03-0.3 mg/mg, and ⬎0.3 mg/mg in 2 collected urine samples, respectively. In the present study, proteinuria was defined as microalbuminuria or macroalbuminuria. Retinopathy was determined through fundus photography by an experienced ophthalmologist who was unaware of the study protocol. Coronary heart disease was defined as acute myocardial infarction, coronary artery disease confirmed by coronary angiography, and presentations of typical angina pectoris. Hypertension was defined as a systolic blood pressure of ⬎140 mm Hg and/or a diastolic blood pressure of ⬎90 mm Hg or if the patients were receiving antihypertensive treatment. Metabolic syndrome was defined as the fulfillment of ⱖ3 of the following 5 criteria: (a) waist circumference ⬎90 cm for men and ⬎80 cm for women (using an ethnicity-specific value for the Chinese or South Asian population); (b) serum triglycerides of ⱖ150 mg/dL or drug treatment of elevated triglycerides; (c) serum high-density lipoprotein level ⬍40 mg/dL in men and ⬍50 mg/dL in women or drug treatment of low high-density lipoprotein cholesterol; (d) elevated blood pressure (systolic blood pressure ⱖ130 mm Hg and/or diastolic blood pressure ⱖ85 mm Hg or a previous diagnosis of hypertension); and (e) increased fasting plasma glucose ⱖ100 mg/dL or a previous diagnosis of DM. Neuropathy was defined as an abnormal vibration perception of the tuning fork.11
Statistical Analysis The data are expressed as the mean ⫾ standard deviation for continuous variables or as numbers and percentages for categorical variables. For comparison, a 2-sample t test was performed to identify the differences of continuous variables between the OAB and non-OAB groups and between the OAB wet and non-OAB groups. The Pearson chi-square test was performed for categorical variables between the OAB and nonOAB groups and the OAB wet and non-OAB groups. Multiple logistic regression analysis was applied to assess the contribution of the risk factors to OAB and OAB wet groups. Multiple logistic regression analysis was also used to adjust for age in the risk factor evaluation. The level of significance was considered at P ⬍ .05. Statistical analysis was performed using Statistical Package for Social Sciences, version 15.0, statistics software (SPSS, Chicago, IL).
RESULTS Prevalence of OAB and OAB Wet Of the 1359 subjects, 22.5% reported having OAB, including 11.7% OAB dry and 10.8% OAB wet (Table 1). The prevalence of OAB was greater in the men than in the women (24.8% vs 20.1%, P ⫽ .040). Significant differences were found in the OABSS among those with no OAB, OAB dry, and OAB wet (2.5 ⫾ 1.4, 5.9 ⫾ 1.6, and 8.9 ⫾ 2.6, respectively, using 1-way analysis of variance, P ⬍ .001). The prevalence of mild, moderate, and 1041
Table 1. Prevalence of overactive bladder Prevalence of OAB Daytime frequency (ⱖ8; score ⱖ1) Nighttime frequency (ⱖ2; score ⱖ2) Urgency (ⱖ1 ⫻ week; score ⱖ2) Urge incontinence (ⱖ1 ⫻ week; score ⱖ2) OAB dry OAB wet OAB severity Mild (OABSS ⱕ5) Moderate (OABSS 6-11) Severe (OABSS ⱖ12)
Men (175 of 707 [24.8])
Women (131 of 652 [20.1])
Total (306 of 1359 [22.5])
337 (47.6) 386 (54.6) 175 (24.8) 84 (11.9) 99 (14.0) 76 (10.7)
293 (44.9) 408 (62.6) 131 (20.1) 92 (14.1) 60 (9.2) 71 (10.9)
630 (46.4) 794 (48.4) 306 (22.5) 176 (13.0) 11.7% 10.8%
54 (7.6) 110 (15.6) 11 (1.6)
24 (3.7) 89 (13.7) 18 (2.8)
78 (5.7) 199 (14.6) 29 (2.1)
OAB, overactive bladder. Data in brackets and parentheses are percentages. 45.0%
35.0%
40.0%
30.0%
35.0%
25.0%
30.0% Male Female
25.0% 20.0%
20.0%
Male
15.0%
Female Total
Total
15.0%
10.0%
10.0%
5.0%
5.0%
0.0%
0.0%
DM duration > 10 yrs & Age > 50 yrs
Љ 40 41-50 51-60 61-70 71-80 Ї 80 yrs yrs yrs yrs yrs yrs
DM duration Љ 10 yrs & Age Љ 50 yrs
Figure 2. OAB versus no OAB (DM duration ⬎10 years and age ⬎50 years).
A 45.0% 40.0%
years and age ⬎50 years compared to those with a DM duration ⱕ10 years and age ⱕ50 years (Fig. 2).
35.0% 30.0% Male Female Total
25.0% 20.0% 15.0% 10.0% 5.0% 0.0% Љ 40 yrs
41-50 51-60 61-70 71-80 Ї 80 yrs yrs yrs yrs yrs
B Figure 1. Prevalence of (A) OAB and (B) OAB wet.
severe OAB was 25.5%, 65.0%, and 9.5%, respectively, among those with OAB. The prevalence of OAB symptoms was 48.4% for nocturia, 46.4% for frequency, 22.5% for urgency, and 13.0% for urge incontinence. The prevalence of OAB and OAB wet increased with increasing age (Fig. 1). The prevalence of OAB and OAB wet was 2.4-fold (P ⫽ .000) and 4.2-fold (P ⫽ .000) greater, respectively, in patients with a DM duration ⬎10 1042
Characteristics and Risk Factors of OAB Versus No OAB The general patient characteristics are listed in Table 2. The OAB group was older (65.1 ⫾ 10.6 vs 61.6 ⫾ 10.7 years, P ⬍ .001), had had a longer duration of DM (11.6 ⫾ 7.2 vs 10.3 ⫾ 6.5 years, P ⫽ .003), more neuropathy (36.7% vs 29.0%, P ⫽ .012), and included more men (57.2% vs 50.5%, P ⫽ .040) than the non-OAB group. No difference was found between the 2 groups with respect to the DM profile, including HbA1c level, lipid profile, uric acid, blood cell count, renal function, hsCRP level, body mass index, and blood pressure. No difference was found between the 2 groups with respect to the presence of hypertension, metabolic syndrome, smoking, drinking, retinopathy, coronary heart disease, stroke, or proteinuria. On multivariate analysis, age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.02-1.05, P ⫽ .007) and male sex (OR 1.43, 95% CI 1.08-1.87, P ⫽ .011) were independent risk factors associated with OAB. The ageadjusted ORs for OAB were also examined using multivariate logistic regression models. Men were 37% more UROLOGY 78 (5), 2011
Table 2. General characteristics of diabetic patients with and without OAB
Characteristic Age (yr) Male sex (%) DM duration (yr) HbA1c (%) Total cholesterol (mg/dL) HDL (mg/dL) LDL (mg/dL) TG (mg/dL) Uric acid WBC count HGB Platelet Mean ACR Creatinine eGFR hs-CRP BMI (kg/m2) Waist circumference (cm) Waist circumference greater than standard* (%) SBP DBP HTN (%) Metabolic syndrome (%) Smoking (%) Alcohol (%) Neuropathy (%) Retinopathy (%) CHD (%) Stroke (%) Proteinuria (%)
P Value Control Control Versus Versus Total OAB OAB Wet
No OAB (Control, n ⫽ 1053)
OAB Dry (n ⫽ 159)
OAB Wet (n ⫽ 147)
Total OAB (Dry ⫹ Wet, n ⫽ 306)
61.6 ⫾ 10.7 50.5 10.3 ⫾ 6.5 7.3 ⫾ 1.2 161.0 ⫾ 30.0 48.6 ⫾ 13.0 91.3 ⫾ 24.9 130.9 ⫾ 118.0 6.2 ⫾ 1.7 6.7 ⫾ 1.4 13.3 ⫾ 2.0 240.1 ⫾ 54.6 0.2 ⫾ 0.8 1.1 ⫾ 0.7 67.8 ⫾ 23.9 1.6 ⫾ 1.9 25.9 ⫾ 3.8 88.7 ⫾ 9.5 62.1
63.0 ⫾ 10.8 62.3 11.5 ⫾ 7.5 7.3 ⫾ 1.2 158.6 ⫾ 34.3 49.0 ⫾ 12.7 89.2 ⫾ 29.9 120.8 ⫾ 81.9 6.3 ⫾ 1.8 6.6 ⫾ 1.4 13.4 ⫾ 1.8 237.1 ⫾ 51.9 0.3 ⫾ 1.0 1.2 ⫾ 0.9 69.9 ⫾ 25.6 1.7 ⫾ 1.9 25.7 ⫾ 3.6 88.6 ⫾ 8.6 56.7
67.4 ⫾ 10.1 51.7 11.8 ⫾ 6.8 7.3 ⫾ 1.1 160.8 ⫾ 29.0 49.8 ⫾ 13.3 90.7 ⫾ 24.4 127.4 ⫾ 62.0 6.2 ⫾ 1.8 6.8 ⫾ 1.5 13.1 ⫾ 1.7 235.6 ⫾ 55.4 0.3 ⫾ 1.0 1.2 ⫾ 0.5 64.0 ⫾ 24.9 1.8 ⫾ 1.9 26.5 ⫾ 4.0 90.9 ⫾ 10.0 72.6
65.1 ⫾ 10.6 57.2 11.6 ⫾ 7.2 7.3 ⫾ 1.2 159.7 ⫾ 31.8 49.4 ⫾ 13.0 89.9 ⫾ 27.3 124.0 ⫾ 73.0 6.2 ⫾ 1.8 6.7 ⫾ 1.4 13.3 ⫾ 1.8 236.4 ⫾ 53.4 0.3 ⫾ 1.0 1.2 ⫾ 0.7 67.0 ⫾ 25.4 1.7 ⫾ 1.9 26.1 ⫾ 3.8 89.7 ⫾ 9.4 64.4
⬍.001 .040 .003 .645 .495 .358 .402 .329 .527 .707 .505 .337 .132 .644 .633 .472 .523 .080 .478
.000 .789 .010 .534 .962 .288 .756 .720 .817 .859 .159 .401 .221 .610 .071 .407 .098 .007 .037
132.3 ⫾ 17.8 74.3 ⫾ 9.9 77.1 71.6 29.0 11.9 29.0 36.2 5.0 3.1 39.5
131.9 ⫾ 18.3 73.9 ⫾ 9.6 76.7 61.6 35.8 7.5 32.4 31.3 6.9 6.3 37.8
134.0 ⫾ 18.6 74.0 ⫾ 10.4 83.7 78.9 22.4 9.5 41.1 36.2 8.2 4.1 44.1
132.9 ⫾ 18.5 74.0 ⫾ 10.0 80.10 69.9 29.4 8.5 36.7 33.7 7.5 5.2 40.90
.623 .585 .226 .567 .880 .098 .012 .294 .096 .068 .666
.294 .734 .070 .064 .100 .405 .003 .992 .116 .491 .284
DM, diabetes mellitus; Hb1Ac, hemoglobin 1Ac; HDL, high-density lipoprotein; LDL, low-density lipoprotein; TG, triglycerides; HGB, hemoglobin; ACR, albumin/creatinine ratio; eGFR ⫽ estimated glomerular filtration rate; hs-CRP, high-sensitivity C-reactive protein; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; HTN, hypertension; CHD, coronary heart disease. * Male, ⬎90 cm; female, ⬎80 cm.
likely to have OAB (OR 1.37, 95% CI 1.01-1.78, P ⫽ .018). Characteristics and Risk Factors of OAB Wet Versus No OAB The OAB wet group was older (67.4 ⫾ 10.1 vs 61.6 ⫾ 10.7 years, P ⬍ .001), had had a longer duration of DM (11.8 ⫾ 6.8 vs 10.3 ⫾ 6.5 years, P ⫽ .010), larger waist circumference (90.9 ⫾ 10.0 vs 88.7 ⫾ 9.5 cm, P ⫽ .007), a greater incidence of a waist circumference greater than the standard, and neuropathy (41.1% vs 29.0%, P ⫽ .003) than the non-OAB group (Table 2). No difference was found between the 2 groups with respect to diabetic profile, including HbA1c level, lipid profile, uric acid, blood cell count, renal function, hs-CRP level, body mass index, and blood pressure. No difference was found between the 2 groups with respect to the presence of hypertension, metabolic syndrome, smoking, drinking, retinopathy, coronary heart disease, stroke, or proteinuria. On multivariate analysis, age (OR 1.04, 95% CI 1.02UROLOGY 78 (5), 2011
1.05, P ⫽ .000) and waist circumference (OR 1.02, 95% CI 1.00-1.03, P ⫽ .013) are independent risk factors associated with OAB wet. Age-adjusted ORs for OAB wet were also examined in multivariate logistic regression models. Waist circumference was still an independent risk factor for OAB wet (OR 1.03, 95% CI 1.01-1.05, P ⫽ .001).
COMMENT Using the OABSS, the results from the present study have demonstrated a high prevalence (22.5%) of OAB in patients with type 2 DM. The moderate degree of OAB was most commonly reported in 14.6% of subjects, followed by mild (5.7%) and severe (2.1%) of OAB. Patients with OAB wet (mean score 8.9 ⫾ 2.6) have more severe symptoms than OAB dry (mean score 5.9 ⫾ 1.6). In our cohort, male sex (24.8%) was more commonly associated with OAB than female sex (20.1%). Age, DM duration, and the presence of neuropathy are significantly different between the non-OAB and OAB dry or OAB 1043
wet groups. On multivariate analysis, age and male sex were independent risk factors for OAB and age and waist circumference were independent risk factors for OAB wet. Irwin et al12 showed that the overall prevalence of OAB was 11.8% in the general population; the rates were similar in men (10.8%) and women (12.8%) and increased with age. Nearly one half of the women and 28.7% of the men who reported symptoms of OAB also reported incontinence.12 A national survey conducted in Japan demonstrated that the estimated prevalence of OAB was 12.4% in the general population ⬎40 years old.13 Yu et al14 reported that the age-adjusted prevalence of OAB was 16.9%, including 4.5% with urge incontinence in a questionnaire survey from 1827 community-dwelling adults in Taiwan. Stewart et al5 reported that the prevalence of OAB symptoms was nearly 1/5, 1/3, and 1/7 for frequency, nocturia, and urgency, respectively, in the general population, and only 6% reported urge incontinence.5 However, in the present study of diabetic population, we showed that all 4 symptoms of OAB had a greater prevalence than the general population and the prevalence of urge incontinence was 13%, more than double that of the general population. The presence of nocturia in the present study was considered an indicator of OAB; however, it can also be associated with benign prostatic hyperplasia or nocturnal polyuria because of poor glycemic control, and the study was unable to control for this. Furthermore, our male group had a greater prevalence of OAB than the female group, which could have resulted because our population’s mean age is ⬎60 years. Irwin et al12 reported that women have a greater prevalence of OAB symptoms than men before ⬍60 years old and men had a greater prevalence of OAB symptoms after 60 years of age. The prostate size correlates with age,15 and the men with DM had a larger prostate than those without DM.16 Men aged ⱖ60 years had a high prevalence of benign prostatic hyperplasia, which often caused bladder outlet obstruction and contributed to the presence OAB.17 The present study further demonstrated that increasing age and DM duration had a greater prevalence of OAB and OAB wet. The prevalence of OAB and OAB wet was 2.4-fold and 4.2-fold greater, respectively, in patients with a DM duration of ⬎10 years and age ⬎50 years. We suggest that patients with DM and these 2 conditions should be screened for OAB by either the urologist and/or diabetiologist. Our study revealed that waist circumference is an independent risk factor for OAB wet. The waist circumference is a marker for central obesity. Obesity has been linked to a more severe OAB state and urinary incontinence.18 A previous study has shown that weight loss caused improvement, not only in stress incontinence, but also in urge incontinence.19 Subak et al19 suggested that excess body weight increases the abdominal pressure 1044
which, in turn, causes or exacerbates detrusor instability and results in urge incontinence. Peripheral neuropathy is a late complication of DM. Neurologic abnormality has been implicated as a major risk factor for OAB. The cause of diabetic neuropathy is multifocal and includes altered metabolism of glucose, ischemia, superoxide-induced free radical formation, impaired axonal transport, and metabolic derangement of the Schwann cell results in segmental demyelination and impairment of nerve conduction.7,20 Peripheral nerve irritation can cause detrusor overactivity or increased bladder sensation.8 The metabolic syndrome and OAB both increase with advancing age and can negatively contribute significantly to the overall quality of life.8 Dyslipidemia and hypertension can decrease blood flow and compromise bladder function. In the present study of patients with DM, the presence of the metabolic syndrome showed a trend to be greater in the group of OAB wet than in the non-OAB group. It suggests that the metabolic syndrome might contribute to more severe OAB with incontinence. Several clinical trials have demonstrated that intensive glycemic control could reduce the complications of DM, and a previous study has shown that glycemic control was associated with the risk of erectile dysfunction in men with DM.21 The present study did not demonstrate a correlation between glycemic control and the risk of OAB. This might have been affected by the standardized glycemic control protocol at a single diabetic center. It would be interesting to serially follow-up the subjects with and without adequate glycemic control to evaluate for development bladder dysfunction. Increasing levels of CRP are associated with OAB, according to a population-based study of men and women.22 We did not observe a correlation between the serum CRP and OAB symptoms in the present study. DM represents a chronic inflammatory condition that might mask the effect of a nonspecific inflammatory marker such as CRP on the presence of OAB. Again, a longitudinal assessment of subjects with DM with and without OAB symptoms over time might offer insight on inflammation, with the development and progression of urologic dysfunction. Traditionally, diabetic bladder dysfunction has been described as a triad of decreased sensation, increased capacity, and poor emptying; however, many inconsistencies with those “classic” findings have been found.23 Ueda et al24 found increased bladder volume at the first sensation to void and a decrease in detrusor contractility, with a resultant increased postvoid residual urine volume in most of the asymptomatic patients with DM, but they also found a 25% incidence of detrusor overactivity. A review by Kaplan et al25 of urodynamic findings in 182 patients with DM revealed 55% with detrusor overactivity, 23% with impaired contractility, 10% with detrusor areflexia, and 11% “indeterminate.” The mixed clinical picture of diabetic bladder dysfunction has also been confirmed in recent large-scale studies, in which DM was UROLOGY 78 (5), 2011
associated with a 30%-70% increased risk of incontinence and a 50% increased risk of urge incontinence in women.26 Taken together, we suggest that urologists and diabetologists should pay attention to the existence of OAB in diabetic population.
CONCLUSIONS In the dedicated diabetic center in which all patients were screened, 22.5% had OAB, and 48.0% of the patients with OAB had incontinence. These findings can help guide the collaboration between urologists and diabetologists to work toward developing screening methods and early treatment of urologic complications in higher risk patients. References 1. Allgot B, Gan D, King H, et al. Diabetes Atlas, Executive Summary, 2nd ed. Brussels: International Diabetes Federation; 2003:58. 2. Chang CH, Shau WY, Jiang YD, et al. Type 2 diabetes prevalence and incidence among adults in Taiwan during 1999-2004: a national health insurance data set study. Diabet Med. 2010;27:636643. 3. Abrams P, Cardozo L, Fall M, et al. The standardization of terminology of lower urinary tract function: report from the Standardization Sub-Committee of the International Continence Society. Neurourol Urodyn. 2002;21:167-178. 4. Yamaguchi C, Sakakibara R, Uchiyama T, et al. Overactive bladder in diabetes: a peripheral or central mechanism? Neurourol Urodyn. 2007;26:807-813. 5. Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003;20:327-336. 6. Lawrence JM, Lukacz ES, Liu IL, Nager CW, Luber KM. Pelvic floor disorders, diabetes, and obesity in women: Findings from the Kaiser Permanente Continence Associated Risk Epidemiology Study. Diabetes Care. 2007;30:2536-2541. 7. Yoshimura N, Chancellor MB, Andersson KE, Christ GJ. Recent advances in understanding the biology of diabetes-associated bladder complications and novel therapy. BJU Int. 2005;95:733-738. 8. Tai HC, Chung SD, Ho CH, et al. Metabolic syndrome components worsen lower urinary tract symptoms in women with type 2 diabetes. J Clin Endocrinol Metab. 2010;95:1143-1150. 9. Homma Y, Yoshida M, Seki N, et al. Symptom assessment tool for overactive bladder syndrome: overactive bladder symptom score. Urology. 2006;68:318-323. 10. Hung MJ, Chou CH, Yen TW, et al. The development and validation of Chinese overactive bladder symptom score (OABSS). Incont Pelvic Floor Dysfunct. 2011;5:17-18.
UROLOGY 78 (5), 2011
11. Meijer J-WG, Smit AJ, Lefrandt JD, et al. Back to basics in diagnosing diabetic polyneuropathy with the tuning fork! Diabetes Care. 2005;28:2201-2205. 12. Irwin DE, Milsom I, Hunskaar S, et al. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol. 2006;50:1306-1315. 13. Homma Y, Yamaguchi O, Hayashi K. An epidemiological survey of overactive bladder symptoms in Japan. BJU Int. 2005;96:13141318. 14. Yu HJ, Liu CY, Lee KL, Lee WC, Chen TH. Overactive bladder syndrome among community-dwelling adults in Taiwan: prevalence, correlates, perception, and treatment seeking. Urol Int. 2006; 77:327-333. 15. Favilla V, Cimino S, Castelli T, et al. Relationship between lower urinary tract symptoms and serum levels of sex hormones in men with symptomatic benign prostatic hyperplasia. BJU Int. 2010;106: 1700-1703. 16. Steers WD. An enlarged prostate is diagnosed more often in patients with type 2 diabetes. Rev Urol. 2002;4:S7-S18. 17. Lee JY, Kim HW, Lee SJ, et al. Comparison of doxazosin with or without tolterodine in men with symptomatic bladder outlet obstruction and an overactive bladder. BJU Int. 2004;94:817-820. 18. Chancellor MB, Oefelein MG, Vasavada S. Obesity is associated with a more severe overactive bladder disease state that is effectively treated with once-daily administration of trospium chloride extended release. Neurourol Urodyn. 2010;29:551-554. 19. Subak LL, Whitcomb E, Shen H, et al. Weight loss: a novel and effective treatment for urinary incontinence. J Urol. 2005;174:190195. 20. Lee WC, Wu HP, Tai TY, Yu HJ, Chiang PH. Investigation of urodynamic characteristics and bladder sensory function in the early stages of diabetic bladder dysfunction in women with type 2 diabetes. J Urol. 2009;181:198-203. 21. Lu CC, Jiann BP, Sun CC, et al. Association of glycemic control with risk of erectile dysfunction in men with type 2 diabetes. J Sex Med. 2009;6:1719-1728. 22. Kupelian V, McVary KT, Barry MJ, et al. Association of C-reactive protein and lower urinary tract symptoms in men and women: results from Boston area community health survey. Urology. 2009; 73:950-957. 23. Frimodt-Moller C. Diabetic cystopathy: epidemiology and related disorders. Ann Intern Med. 1980;92:318-321. 24. Ueda T, Yoshimura N, Yoshida O. Diabetic cystopathy: relationship to autonomic neuropathy detected by sympathetic skin response. J Urol. 1997;157:580-584. 25. Kaplan SA, Te AE, Blaivas JG. Urodynamic findings in patients with diabetic cystopathy. J Urol. 1995;153:342-344. 26. Brown JS, Nyberg LM, Kusek JW, et al. Proceedings of the National Institute of Diabetes and Digestive and Kidney Diseases International Symposium on Epidemiologic Issues in Urinary Incontinence in Women. Am J Obstet Gynecol. 2003;188:S77-S88.
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RESULTS
CONCLUSION
To evaluate overactive bladder (OAB, dry and wet) and the associated risk factors of OAB wet (with incontinence) in type 2 diabetes. A self-administered questionnaire containing the OAB symptom score (OABSS, 0-15, with higher numbers indicating an increasing severity of symptoms) was obtained from subjects with type 2 diabetes at a dedicated diabetic center. The association of age, sex, duration of diabetes, body mass index, waist circumference, glycated hemoglobin level, high-sensitive C-reactive protein level, and diabetes-associated complications to the risk of OAB and OAB wet was evaluated. Of 1359 consecutive subjects, 22.5% reported having OAB, with 11.7% reporting OAB dry and 10.8% OAB wet. The difference in symptom severity was statistically significant among those without OAB and those with OAB dry and OAB wet (OABSS 2.5 ⫾ 1.4, 5.9 ⫾ 1.6, and 8.9 ⫾ 2.6, respectively). The prevalence of OAB and OAB wet was 2.4-fold and 4.2-fold greater, respectively, in patients with a diabetes duration ⬎10 years and age ⬎50 years. Age and male sex and age and waist circumference were independent risk factors for OAB and OAB wet, respectively, after multivariate analysis. Glycated hemoglobin and high-sensitivity C-reactive protein levels were similar between patients with diabetes patients with and without OAB. In the dedicated diabetic center in which all patients were screened, 22.5% had OAB, and 48.0% of those with OAB had incontinence. These findings can help guide the collaboration between urologists and diabetologists to work toward developing screening for, and early treatment of, urologic complications in higher risk patients. UROLOGY 78: 1040 –1045, 2011. © 2011 Elsevier Inc.
D
iabetes mellitus (DM), a chronic metabolic condition, is an increasing health concern across the world with significant medical and health economic issues. According to the International Diabetes Federation, the North American Region has a DM prevalence of 7.9% in the adult population.1 Using Taiwan National Health Insurance claims data, Chang et al2 reported that the prevalence of type 2 DM among those aged ⬎20 years was 6.8% in Taiwan. Studies have shown that overactive bladder (OAB) syndrome, defined as urgency (complaint of a sudden compelling desire to pass urine that is difficult to defer), with or without inconti-
Funding Support: This study was supported by grant CMRPG 860381. From the Divisions of Metabolism; and Urology and Department of Medical Research, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; and Department of Urology, William Beaumont Hospital, Royal Oak, Michigan Reprint requests: Yao-Chi Chuang, M.D., Division of Urology, Department of Surgery Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung, 123 Ta Pei Road, Niao-Sung, Hsiang, Kaohsiung Hsien, Taiwan. E-mail: [email protected] Submitted: April 2, 2011, accepted (with revisions): May 13, 2011
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© 2011 Elsevier Inc. All Rights Reserved
nence, usually with urinary frequency and nocturia,3 commonly occurs in patients with DM and have a significant effect on society.4,5 A survey of 3962 women demonstrated that OAB affects 21.4% of diabetic women compared to only 12.5% of nondiabetic women.6 However, the overall prevalence of OAB in diabetic patients, including the male population, has rarely been reported. Diabetologists and urologists practice in different fields and often treat OAB and DM as separate entities without correlation. Furthermore, the presence of OAB wet (incontinence) has a stronger effect on quality of life than OAB dry (no incontinence). It would be important to assess all diabetic patients for the presence or absence of OAB symptoms, especially with incontinence, and help determine who would be at risk and who should be screened. DM is associated with systemic inflammation, neuropathy, cardiovascular complications, and metabolic syndrome, all of which have been linked to OAB.7,8 To more clearly understand the association between OAB and DM, we conduct a cross-sectional study to examine the relationship between OAB and markers of DM, in0090-4295/11/$36.00 doi:10.1016/j.urology.2011.05.017
cluding microvascular complications of DM (eg, retinopathy, neuropathy, and nephropathy), macrovascular complications (eg, coronary artery disease and stroke), diabetic control (glycated hemoglobin [HbA1c]), inflammatory condition (high-sensitivity C-reactive protein [hs-CRP]), obesity (eg, waist circumference, body mass index), and metabolic syndrome.
MATERIAL AND METHODS Patient Enrollment A cross-sectional study was conducted among 1715 consecutive diabetic patients attending a single outpatient diabetic clinic managed by 1 diabetologist (R.T.L.) at Chang Gung Memorial Hospital-Kaohsiung Medical Center from April 2008 to November 2008. The study only included subjects who had already been enrolled in the diabetic clinic for ⬎1 year. Of all the patients, 46 were diagnosed with type 1 DM and were excluded from the present study. Of the patients, 1359 agreed to complete the self-administered questionnaires composed of demographic data and a validated Chinese version of the OAB symptom score (OABSS). Diabetic patients with new-onset neurologic disorders (eg, stroke, Parkinsonism, spinal cord injury, and multiple sclerosis), active urinary tract infections, previous major pelvic surgery, or evidence of pelvic organ prolapse were excluded from the present study. The institutional review board approved the study protocol, and all participants gave their written informed consent.
Assessment for OAB OABSS, a 4-item questionnaire developed by Homma et al,9 was used to assess the symptoms of OAB. The OABSS total score is a sum of the 4 item scores from a self-administered questionnaire of 4 symptoms: daytime frequency (score 0-2), nighttime frequency (score 0-3), urgency (score 0-5), and urgency incontinence (score 0-5). In the present study, the patients with an urgency score of ⱖ2 and sum score of ⱖ3 were considered to have OAB. Of the patients with OAB, those with an urgency incontinence score of ⱖ2 (once a week or more) were considered to have OAB wet. The sum score (0-15, with greater numbers indicating increasing severity of symptoms) was categorized as none (score 0-2), mild (score 3-5), moderate (score 6-11), or severe (score ⱖ12) OAB.9 The OABSS has been validated and adapted linguistically and psychometrically for their Chinese counterparts in Taiwan by Taiwanese Continence Society.10
Clinical Profiles and Definition Each patient participated in a detailed interview regarding their personal disease, smoking, and drinking history by 2 trained interviewers. The parameters evaluated were age, duration of DM, microvascular complications of DM (ie, retinopathy, neuropathy, and nephropathy), macrovascular complications of DM (ie, coronary artery disease and stroke), diabetic control, inflammatory condition (hs-CRP), body mass index (calculated as the body weight in kilograms divided by the square of the body height in meters), waist circumference, metabolic syndrome, and biochemical data, including total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, uric acid, serum creatinine, HbA1c, hsCRP, complete blood count, and differential count. UROLOGY 78 (5), 2011
The estimated glomerular filtration rate was calculated using the modified Diet and Renal Disease equation. The urinary albumin concentration was measured by random daytime urine samples. Albumin excretion rate was defined entirely by calculation of the albumin/creatinine ratio in urine specimen. The definition of normal albuminuria, microalbuminuria, and macroalbuminuria was an albumin/creatinine ratio ⬍0.03 mg/mg once in one collected urine sample, 0.03-0.3 mg/mg, and ⬎0.3 mg/mg in 2 collected urine samples, respectively. In the present study, proteinuria was defined as microalbuminuria or macroalbuminuria. Retinopathy was determined through fundus photography by an experienced ophthalmologist who was unaware of the study protocol. Coronary heart disease was defined as acute myocardial infarction, coronary artery disease confirmed by coronary angiography, and presentations of typical angina pectoris. Hypertension was defined as a systolic blood pressure of ⬎140 mm Hg and/or a diastolic blood pressure of ⬎90 mm Hg or if the patients were receiving antihypertensive treatment. Metabolic syndrome was defined as the fulfillment of ⱖ3 of the following 5 criteria: (a) waist circumference ⬎90 cm for men and ⬎80 cm for women (using an ethnicity-specific value for the Chinese or South Asian population); (b) serum triglycerides of ⱖ150 mg/dL or drug treatment of elevated triglycerides; (c) serum high-density lipoprotein level ⬍40 mg/dL in men and ⬍50 mg/dL in women or drug treatment of low high-density lipoprotein cholesterol; (d) elevated blood pressure (systolic blood pressure ⱖ130 mm Hg and/or diastolic blood pressure ⱖ85 mm Hg or a previous diagnosis of hypertension); and (e) increased fasting plasma glucose ⱖ100 mg/dL or a previous diagnosis of DM. Neuropathy was defined as an abnormal vibration perception of the tuning fork.11
Statistical Analysis The data are expressed as the mean ⫾ standard deviation for continuous variables or as numbers and percentages for categorical variables. For comparison, a 2-sample t test was performed to identify the differences of continuous variables between the OAB and non-OAB groups and between the OAB wet and non-OAB groups. The Pearson chi-square test was performed for categorical variables between the OAB and nonOAB groups and the OAB wet and non-OAB groups. Multiple logistic regression analysis was applied to assess the contribution of the risk factors to OAB and OAB wet groups. Multiple logistic regression analysis was also used to adjust for age in the risk factor evaluation. The level of significance was considered at P ⬍ .05. Statistical analysis was performed using Statistical Package for Social Sciences, version 15.0, statistics software (SPSS, Chicago, IL).
RESULTS Prevalence of OAB and OAB Wet Of the 1359 subjects, 22.5% reported having OAB, including 11.7% OAB dry and 10.8% OAB wet (Table 1). The prevalence of OAB was greater in the men than in the women (24.8% vs 20.1%, P ⫽ .040). Significant differences were found in the OABSS among those with no OAB, OAB dry, and OAB wet (2.5 ⫾ 1.4, 5.9 ⫾ 1.6, and 8.9 ⫾ 2.6, respectively, using 1-way analysis of variance, P ⬍ .001). The prevalence of mild, moderate, and 1041
Table 1. Prevalence of overactive bladder Prevalence of OAB Daytime frequency (ⱖ8; score ⱖ1) Nighttime frequency (ⱖ2; score ⱖ2) Urgency (ⱖ1 ⫻ week; score ⱖ2) Urge incontinence (ⱖ1 ⫻ week; score ⱖ2) OAB dry OAB wet OAB severity Mild (OABSS ⱕ5) Moderate (OABSS 6-11) Severe (OABSS ⱖ12)
Men (175 of 707 [24.8])
Women (131 of 652 [20.1])
Total (306 of 1359 [22.5])
337 (47.6) 386 (54.6) 175 (24.8) 84 (11.9) 99 (14.0) 76 (10.7)
293 (44.9) 408 (62.6) 131 (20.1) 92 (14.1) 60 (9.2) 71 (10.9)
630 (46.4) 794 (48.4) 306 (22.5) 176 (13.0) 11.7% 10.8%
54 (7.6) 110 (15.6) 11 (1.6)
24 (3.7) 89 (13.7) 18 (2.8)
78 (5.7) 199 (14.6) 29 (2.1)
OAB, overactive bladder. Data in brackets and parentheses are percentages. 45.0%
35.0%
40.0%
30.0%
35.0%
25.0%
30.0% Male Female
25.0% 20.0%
20.0%
Male
15.0%
Female Total
Total
15.0%
10.0%
10.0%
5.0%
5.0%
0.0%
0.0%
DM duration > 10 yrs & Age > 50 yrs
Љ 40 41-50 51-60 61-70 71-80 Ї 80 yrs yrs yrs yrs yrs yrs
DM duration Љ 10 yrs & Age Љ 50 yrs
Figure 2. OAB versus no OAB (DM duration ⬎10 years and age ⬎50 years).
A 45.0% 40.0%
years and age ⬎50 years compared to those with a DM duration ⱕ10 years and age ⱕ50 years (Fig. 2).
35.0% 30.0% Male Female Total
25.0% 20.0% 15.0% 10.0% 5.0% 0.0% Љ 40 yrs
41-50 51-60 61-70 71-80 Ї 80 yrs yrs yrs yrs yrs
B Figure 1. Prevalence of (A) OAB and (B) OAB wet.
severe OAB was 25.5%, 65.0%, and 9.5%, respectively, among those with OAB. The prevalence of OAB symptoms was 48.4% for nocturia, 46.4% for frequency, 22.5% for urgency, and 13.0% for urge incontinence. The prevalence of OAB and OAB wet increased with increasing age (Fig. 1). The prevalence of OAB and OAB wet was 2.4-fold (P ⫽ .000) and 4.2-fold (P ⫽ .000) greater, respectively, in patients with a DM duration ⬎10 1042
Characteristics and Risk Factors of OAB Versus No OAB The general patient characteristics are listed in Table 2. The OAB group was older (65.1 ⫾ 10.6 vs 61.6 ⫾ 10.7 years, P ⬍ .001), had had a longer duration of DM (11.6 ⫾ 7.2 vs 10.3 ⫾ 6.5 years, P ⫽ .003), more neuropathy (36.7% vs 29.0%, P ⫽ .012), and included more men (57.2% vs 50.5%, P ⫽ .040) than the non-OAB group. No difference was found between the 2 groups with respect to the DM profile, including HbA1c level, lipid profile, uric acid, blood cell count, renal function, hsCRP level, body mass index, and blood pressure. No difference was found between the 2 groups with respect to the presence of hypertension, metabolic syndrome, smoking, drinking, retinopathy, coronary heart disease, stroke, or proteinuria. On multivariate analysis, age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.02-1.05, P ⫽ .007) and male sex (OR 1.43, 95% CI 1.08-1.87, P ⫽ .011) were independent risk factors associated with OAB. The ageadjusted ORs for OAB were also examined using multivariate logistic regression models. Men were 37% more UROLOGY 78 (5), 2011
Table 2. General characteristics of diabetic patients with and without OAB
Characteristic Age (yr) Male sex (%) DM duration (yr) HbA1c (%) Total cholesterol (mg/dL) HDL (mg/dL) LDL (mg/dL) TG (mg/dL) Uric acid WBC count HGB Platelet Mean ACR Creatinine eGFR hs-CRP BMI (kg/m2) Waist circumference (cm) Waist circumference greater than standard* (%) SBP DBP HTN (%) Metabolic syndrome (%) Smoking (%) Alcohol (%) Neuropathy (%) Retinopathy (%) CHD (%) Stroke (%) Proteinuria (%)
P Value Control Control Versus Versus Total OAB OAB Wet
No OAB (Control, n ⫽ 1053)
OAB Dry (n ⫽ 159)
OAB Wet (n ⫽ 147)
Total OAB (Dry ⫹ Wet, n ⫽ 306)
61.6 ⫾ 10.7 50.5 10.3 ⫾ 6.5 7.3 ⫾ 1.2 161.0 ⫾ 30.0 48.6 ⫾ 13.0 91.3 ⫾ 24.9 130.9 ⫾ 118.0 6.2 ⫾ 1.7 6.7 ⫾ 1.4 13.3 ⫾ 2.0 240.1 ⫾ 54.6 0.2 ⫾ 0.8 1.1 ⫾ 0.7 67.8 ⫾ 23.9 1.6 ⫾ 1.9 25.9 ⫾ 3.8 88.7 ⫾ 9.5 62.1
63.0 ⫾ 10.8 62.3 11.5 ⫾ 7.5 7.3 ⫾ 1.2 158.6 ⫾ 34.3 49.0 ⫾ 12.7 89.2 ⫾ 29.9 120.8 ⫾ 81.9 6.3 ⫾ 1.8 6.6 ⫾ 1.4 13.4 ⫾ 1.8 237.1 ⫾ 51.9 0.3 ⫾ 1.0 1.2 ⫾ 0.9 69.9 ⫾ 25.6 1.7 ⫾ 1.9 25.7 ⫾ 3.6 88.6 ⫾ 8.6 56.7
67.4 ⫾ 10.1 51.7 11.8 ⫾ 6.8 7.3 ⫾ 1.1 160.8 ⫾ 29.0 49.8 ⫾ 13.3 90.7 ⫾ 24.4 127.4 ⫾ 62.0 6.2 ⫾ 1.8 6.8 ⫾ 1.5 13.1 ⫾ 1.7 235.6 ⫾ 55.4 0.3 ⫾ 1.0 1.2 ⫾ 0.5 64.0 ⫾ 24.9 1.8 ⫾ 1.9 26.5 ⫾ 4.0 90.9 ⫾ 10.0 72.6
65.1 ⫾ 10.6 57.2 11.6 ⫾ 7.2 7.3 ⫾ 1.2 159.7 ⫾ 31.8 49.4 ⫾ 13.0 89.9 ⫾ 27.3 124.0 ⫾ 73.0 6.2 ⫾ 1.8 6.7 ⫾ 1.4 13.3 ⫾ 1.8 236.4 ⫾ 53.4 0.3 ⫾ 1.0 1.2 ⫾ 0.7 67.0 ⫾ 25.4 1.7 ⫾ 1.9 26.1 ⫾ 3.8 89.7 ⫾ 9.4 64.4
⬍.001 .040 .003 .645 .495 .358 .402 .329 .527 .707 .505 .337 .132 .644 .633 .472 .523 .080 .478
.000 .789 .010 .534 .962 .288 .756 .720 .817 .859 .159 .401 .221 .610 .071 .407 .098 .007 .037
132.3 ⫾ 17.8 74.3 ⫾ 9.9 77.1 71.6 29.0 11.9 29.0 36.2 5.0 3.1 39.5
131.9 ⫾ 18.3 73.9 ⫾ 9.6 76.7 61.6 35.8 7.5 32.4 31.3 6.9 6.3 37.8
134.0 ⫾ 18.6 74.0 ⫾ 10.4 83.7 78.9 22.4 9.5 41.1 36.2 8.2 4.1 44.1
132.9 ⫾ 18.5 74.0 ⫾ 10.0 80.10 69.9 29.4 8.5 36.7 33.7 7.5 5.2 40.90
.623 .585 .226 .567 .880 .098 .012 .294 .096 .068 .666
.294 .734 .070 .064 .100 .405 .003 .992 .116 .491 .284
DM, diabetes mellitus; Hb1Ac, hemoglobin 1Ac; HDL, high-density lipoprotein; LDL, low-density lipoprotein; TG, triglycerides; HGB, hemoglobin; ACR, albumin/creatinine ratio; eGFR ⫽ estimated glomerular filtration rate; hs-CRP, high-sensitivity C-reactive protein; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; HTN, hypertension; CHD, coronary heart disease. * Male, ⬎90 cm; female, ⬎80 cm.
likely to have OAB (OR 1.37, 95% CI 1.01-1.78, P ⫽ .018). Characteristics and Risk Factors of OAB Wet Versus No OAB The OAB wet group was older (67.4 ⫾ 10.1 vs 61.6 ⫾ 10.7 years, P ⬍ .001), had had a longer duration of DM (11.8 ⫾ 6.8 vs 10.3 ⫾ 6.5 years, P ⫽ .010), larger waist circumference (90.9 ⫾ 10.0 vs 88.7 ⫾ 9.5 cm, P ⫽ .007), a greater incidence of a waist circumference greater than the standard, and neuropathy (41.1% vs 29.0%, P ⫽ .003) than the non-OAB group (Table 2). No difference was found between the 2 groups with respect to diabetic profile, including HbA1c level, lipid profile, uric acid, blood cell count, renal function, hs-CRP level, body mass index, and blood pressure. No difference was found between the 2 groups with respect to the presence of hypertension, metabolic syndrome, smoking, drinking, retinopathy, coronary heart disease, stroke, or proteinuria. On multivariate analysis, age (OR 1.04, 95% CI 1.02UROLOGY 78 (5), 2011
1.05, P ⫽ .000) and waist circumference (OR 1.02, 95% CI 1.00-1.03, P ⫽ .013) are independent risk factors associated with OAB wet. Age-adjusted ORs for OAB wet were also examined in multivariate logistic regression models. Waist circumference was still an independent risk factor for OAB wet (OR 1.03, 95% CI 1.01-1.05, P ⫽ .001).
COMMENT Using the OABSS, the results from the present study have demonstrated a high prevalence (22.5%) of OAB in patients with type 2 DM. The moderate degree of OAB was most commonly reported in 14.6% of subjects, followed by mild (5.7%) and severe (2.1%) of OAB. Patients with OAB wet (mean score 8.9 ⫾ 2.6) have more severe symptoms than OAB dry (mean score 5.9 ⫾ 1.6). In our cohort, male sex (24.8%) was more commonly associated with OAB than female sex (20.1%). Age, DM duration, and the presence of neuropathy are significantly different between the non-OAB and OAB dry or OAB 1043
wet groups. On multivariate analysis, age and male sex were independent risk factors for OAB and age and waist circumference were independent risk factors for OAB wet. Irwin et al12 showed that the overall prevalence of OAB was 11.8% in the general population; the rates were similar in men (10.8%) and women (12.8%) and increased with age. Nearly one half of the women and 28.7% of the men who reported symptoms of OAB also reported incontinence.12 A national survey conducted in Japan demonstrated that the estimated prevalence of OAB was 12.4% in the general population ⬎40 years old.13 Yu et al14 reported that the age-adjusted prevalence of OAB was 16.9%, including 4.5% with urge incontinence in a questionnaire survey from 1827 community-dwelling adults in Taiwan. Stewart et al5 reported that the prevalence of OAB symptoms was nearly 1/5, 1/3, and 1/7 for frequency, nocturia, and urgency, respectively, in the general population, and only 6% reported urge incontinence.5 However, in the present study of diabetic population, we showed that all 4 symptoms of OAB had a greater prevalence than the general population and the prevalence of urge incontinence was 13%, more than double that of the general population. The presence of nocturia in the present study was considered an indicator of OAB; however, it can also be associated with benign prostatic hyperplasia or nocturnal polyuria because of poor glycemic control, and the study was unable to control for this. Furthermore, our male group had a greater prevalence of OAB than the female group, which could have resulted because our population’s mean age is ⬎60 years. Irwin et al12 reported that women have a greater prevalence of OAB symptoms than men before ⬍60 years old and men had a greater prevalence of OAB symptoms after 60 years of age. The prostate size correlates with age,15 and the men with DM had a larger prostate than those without DM.16 Men aged ⱖ60 years had a high prevalence of benign prostatic hyperplasia, which often caused bladder outlet obstruction and contributed to the presence OAB.17 The present study further demonstrated that increasing age and DM duration had a greater prevalence of OAB and OAB wet. The prevalence of OAB and OAB wet was 2.4-fold and 4.2-fold greater, respectively, in patients with a DM duration of ⬎10 years and age ⬎50 years. We suggest that patients with DM and these 2 conditions should be screened for OAB by either the urologist and/or diabetiologist. Our study revealed that waist circumference is an independent risk factor for OAB wet. The waist circumference is a marker for central obesity. Obesity has been linked to a more severe OAB state and urinary incontinence.18 A previous study has shown that weight loss caused improvement, not only in stress incontinence, but also in urge incontinence.19 Subak et al19 suggested that excess body weight increases the abdominal pressure 1044
which, in turn, causes or exacerbates detrusor instability and results in urge incontinence. Peripheral neuropathy is a late complication of DM. Neurologic abnormality has been implicated as a major risk factor for OAB. The cause of diabetic neuropathy is multifocal and includes altered metabolism of glucose, ischemia, superoxide-induced free radical formation, impaired axonal transport, and metabolic derangement of the Schwann cell results in segmental demyelination and impairment of nerve conduction.7,20 Peripheral nerve irritation can cause detrusor overactivity or increased bladder sensation.8 The metabolic syndrome and OAB both increase with advancing age and can negatively contribute significantly to the overall quality of life.8 Dyslipidemia and hypertension can decrease blood flow and compromise bladder function. In the present study of patients with DM, the presence of the metabolic syndrome showed a trend to be greater in the group of OAB wet than in the non-OAB group. It suggests that the metabolic syndrome might contribute to more severe OAB with incontinence. Several clinical trials have demonstrated that intensive glycemic control could reduce the complications of DM, and a previous study has shown that glycemic control was associated with the risk of erectile dysfunction in men with DM.21 The present study did not demonstrate a correlation between glycemic control and the risk of OAB. This might have been affected by the standardized glycemic control protocol at a single diabetic center. It would be interesting to serially follow-up the subjects with and without adequate glycemic control to evaluate for development bladder dysfunction. Increasing levels of CRP are associated with OAB, according to a population-based study of men and women.22 We did not observe a correlation between the serum CRP and OAB symptoms in the present study. DM represents a chronic inflammatory condition that might mask the effect of a nonspecific inflammatory marker such as CRP on the presence of OAB. Again, a longitudinal assessment of subjects with DM with and without OAB symptoms over time might offer insight on inflammation, with the development and progression of urologic dysfunction. Traditionally, diabetic bladder dysfunction has been described as a triad of decreased sensation, increased capacity, and poor emptying; however, many inconsistencies with those “classic” findings have been found.23 Ueda et al24 found increased bladder volume at the first sensation to void and a decrease in detrusor contractility, with a resultant increased postvoid residual urine volume in most of the asymptomatic patients with DM, but they also found a 25% incidence of detrusor overactivity. A review by Kaplan et al25 of urodynamic findings in 182 patients with DM revealed 55% with detrusor overactivity, 23% with impaired contractility, 10% with detrusor areflexia, and 11% “indeterminate.” The mixed clinical picture of diabetic bladder dysfunction has also been confirmed in recent large-scale studies, in which DM was UROLOGY 78 (5), 2011
associated with a 30%-70% increased risk of incontinence and a 50% increased risk of urge incontinence in women.26 Taken together, we suggest that urologists and diabetologists should pay attention to the existence of OAB in diabetic population.
CONCLUSIONS In the dedicated diabetic center in which all patients were screened, 22.5% had OAB, and 48.0% of the patients with OAB had incontinence. These findings can help guide the collaboration between urologists and diabetologists to work toward developing screening methods and early treatment of urologic complications in higher risk patients. References 1. Allgot B, Gan D, King H, et al. Diabetes Atlas, Executive Summary, 2nd ed. Brussels: International Diabetes Federation; 2003:58. 2. Chang CH, Shau WY, Jiang YD, et al. Type 2 diabetes prevalence and incidence among adults in Taiwan during 1999-2004: a national health insurance data set study. Diabet Med. 2010;27:636643. 3. Abrams P, Cardozo L, Fall M, et al. The standardization of terminology of lower urinary tract function: report from the Standardization Sub-Committee of the International Continence Society. Neurourol Urodyn. 2002;21:167-178. 4. Yamaguchi C, Sakakibara R, Uchiyama T, et al. Overactive bladder in diabetes: a peripheral or central mechanism? Neurourol Urodyn. 2007;26:807-813. 5. Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003;20:327-336. 6. Lawrence JM, Lukacz ES, Liu IL, Nager CW, Luber KM. Pelvic floor disorders, diabetes, and obesity in women: Findings from the Kaiser Permanente Continence Associated Risk Epidemiology Study. Diabetes Care. 2007;30:2536-2541. 7. Yoshimura N, Chancellor MB, Andersson KE, Christ GJ. Recent advances in understanding the biology of diabetes-associated bladder complications and novel therapy. BJU Int. 2005;95:733-738. 8. Tai HC, Chung SD, Ho CH, et al. Metabolic syndrome components worsen lower urinary tract symptoms in women with type 2 diabetes. J Clin Endocrinol Metab. 2010;95:1143-1150. 9. Homma Y, Yoshida M, Seki N, et al. Symptom assessment tool for overactive bladder syndrome: overactive bladder symptom score. Urology. 2006;68:318-323. 10. Hung MJ, Chou CH, Yen TW, et al. The development and validation of Chinese overactive bladder symptom score (OABSS). Incont Pelvic Floor Dysfunct. 2011;5:17-18.
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