Wei-Chia Lee

Prevalence of Overactive Bladder and Associated Risk Factors in 1359 Patients With Type 2 Diabetes

OBJECTIVE To evaluate overactive bladder (OAB, dry and wet) and the associated risk factors of OAB wet (with incontinence) in type 2 diabetes. METHODS 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. RESULTS 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. CONCLUSION 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.

Preliminary results of prostate vaporization in the treatment of benign prostatic hyperplasia by using a 200-W high-intensity diode laser.

OBJECTIVES To evaluate the efficacy and safety of a 200-W high-intensity diode laser in the treatment of benign prostatic hyperplasia. METHODS The prostate was vaporized by using a side-firing laser fiber (diode laser: power, 150-200 W; wavelength, 980 nm; Limmer, Germany). The following parameters were assessed at baseline, and after a follow-up period of 1- and 6 months: International Prostate Symptom Score, maximum uroflow rate, postvoid residual urine volume, and quality of life score. Prostate volume and prostate-specific antigen levels were assessed at baseline and 6 months postoperatively. RESULTS This study included 55 patients diagnosed with lower urinary tract symptoms secondary to BPH, who were treated between December 2007 and July 2008. The recatheterization rate was 10.9%. None of these patients required a blood transfusion or had transurethral resection syndrome. Statistically significant improvements (P < .001) were observed in the values of International Prostate Symptom Score, Q(max), postvoid residual urine volume, and quality of life score at 1- and 6 months of follow-up as compared with the respective baseline values. Transient urge incontinence was noted in 8 patients (8/55, 14.5%).Sloughing of necrotic tissues was observed on cystoscopy in 8 patients within several weeks or months after the operation. The retreatment rate (secondary transurethral resection of the prostate) was 7.3%. CONCLUSIONS From our preliminary data, it was evident that diode laser prostatectomy can achieve excellent hemostasis, and provide immediate relief from obstructive voiding symptoms. However, the postoperative irritative symptoms and sloughing of necrotic tissues remained to be an important issue that needed to be resolved.

Melatonin prevents maternal fructose intake-induced programmed hypertension in the offspring: roles of nitric oxide and arachidonic acid metabolites

Fructose intake has increased globally and is linked to hypertension. Melatonin was reported to prevent hypertension development. In this study, we examined whether maternal high fructose (HF) intake causes programmed hypertension and whether melatonin therapy confers protection against the process, with a focus on the link to epigenetic changes in the kidney using next‐generation RNA sequencing (NGS) technology. Pregnant Sprague–Dawley rats received regular chow or chow supplemented with HF (60% diet by weight) alone or with additional 0.01% melatonin in drinking water during the whole period of pregnancy and lactation. Male offspring were assigned to four groups: control, HF, control + melatonin (M), and HF + M. Maternal HF caused increases in blood pressure (BP) in the 12‐wk‐old offspring. Melatonin therapy blunted the HF‐induced programmed hypertension and increased nitric oxide (NO) level in the kidney. The identified differential expressed gene (DEGs) that are related to regulation of BP included Ephx2, Col1a2, Gucy1a3, Npr3, Aqp2, Hba‐a2, and Ptgs1. Of which, melatonin therapy inhibited expression and activity of soluble epoxide hydrolase (SEH, Ephx2 gene encoding protein). In addition, we found genes in arachidonic acid metabolism were potentially involved in the HF‐induced programmed hypertension and were affected by melatonin therapy. Together, our data suggest that the beneficial effects of melatonin are attributed to its ability to increase NO level in the kidney, epigenetic regulation of genes related to BP control, and inhibition of SEH expression. The roles of DEGs by the NGS in long‐term epigenetic changes in the adult offspring kidney require further clarification.

Asymmetric dimethylarginine is associated with developmental programming of adult kidney disease and hypertension in offspring of streptozotocin-treated mothers.

Diabetes mellitus complicates pregnancies, leading to diseases in adult life in the offspring. Asymmetric dimethylarginine (ADMA) is increased in diabetes mellitus, kidney disease, and hypertension. We tested whether maternal diabetes causes increased ADMA in rats, resulting in kidney disease and hypertension in the adult offspring, and whether these can be prevented by maternal citrulline supplementation. Newborn female and pregnant Sprague-Dawley rats were injected with streptozotocin (STZ), which made up the nSTZ and STZ models, respectively. For the STZ model, 4 groups of male offspring were killed at age 3 months: the control, STZ, and Cit and STZ+Cit (control and STZ rats treated with 0.25% l-citrulline solution, respectively) groups. The nSTZ rats had lower nephron numbers. The renal level of ADMA was higher in the nSTZ rats than in controls. The STZ group developed kidney injury, renal hypertrophy, and elevated blood pressure at the age of 12 weeks. These conditions were found to be associated with increased ADMA levels, decreased nitric oxide (NO) production, and decreased dimethylarginine dimethylaminohydrolase (DDAH) activity in the kidney. In addition, ADMA caused a nephron deficit in cultured rat metanephroi. Maternal citrulline supplementation prevented hypertension and kidney injury, increased the renal DDAH-2 protein level, and restored the levels of ADMA and NO in the STZ+Cit group. Reduced nephron number and increased ADMA contribute to adult kidney disease and hypertension in offspring of mothers with STZ-induced diabetes. Manipulation of the ADMA-NO pathway by citrulline supplementation may be a potential approach to prevent these conditions.

Sensory dysfunction of bladder mucosa and bladder oversensitivity in a rat model of metabolic syndrome.

Purpose To study the role of sensory dysfunction of bladder mucosa in bladder oversensitivity of rats with metabolic syndrome. Materials and Methods Female Wistar rats were fed a fructose-rich diet (60%) or a normal diet for 3 months. Based on cystometry, the fructose-fed rats (FFRs) were divided into a group with normal detrusor function or detrusor overactivity (DO). Acidic adenosine triphosphate (ATP) solution (5mM, pH 3.3) was used to elicit reflex micturition. Cystometric parameters were evaluated before and after drug administration. Functional proteins of the bladder mucosa were assessed by western blotting. Results Compared to the controls, intravesical acidic ATP solution instillation induced a significant increase in provoked phasic contractions in both FFR groups and a significant decrease in the mean functional bladder capacity of group DO. Pretreatment with capsaicin for C-fiber desentization, intravesical liposome for mucosal protection, or intravenous pyridoxal 5-phosphate 6-azophenyl-2′,4′-disulfonic acid for antagonized purinergic receptors can interfere with the urodynamic effects of intravesical ATP in FFRs and controls. Over-expression of TRPV1, P2X3, and iNOS proteins, and down-regulation of eNOS proteins were observed in the bladder mucosa of both fructose-fed groups. Conclusions Alterations of sensory receptors and enzymes in the bladder mucosa, including over-expression of TRPV1, P2X3, and iNOS proteins, can precipitate the emergence of bladder phasic contractions and oversensitivity through the activation of C-afferents during acidic ATP solution stimulation in FFRs. The down-regulation of eNOS protein in the bladder mucosa of FFRs may lead to a failure to suppress bladder oversensitivity and phasic contractions. Sensory dysfunction of bladder mucosa and DO causing by metabolic syndrome are easier to elicit bladder oversensitivity to certain urothelium stimuli.

Maternal fructose-intake-induced renal programming in adult male offspring

Nutrition in pregnancy can elicit long-term effects on the health of offspring. Although fructose consumption has increased globally and is linked to metabolic syndrome, little is known about the long-term effects of maternal high-fructose (HF) exposure during gestation and lactation, especially on renal programming. We examined potential key genes and pathways that are associated with HF-induced renal programming using whole-genome RNA next-generation sequencing (NGS) to quantify the abundance of RNA transcripts in kidneys from 1-day-, 3-week-, and 3-month-old male offspring. Pregnant Sprague-Dawley rats received regular chow or chow supplemented with HF (60% diet by weight) during the entire period of pregnancy and lactation. Male offspring exhibited programmed hypertension at 3 months of age. Maternal HF intake modified over 200 renal transcripts from nephrogenesis stage to adulthood. We observed that 20 differentially expressed genes identified in 1-day-old kidney are related to regulation of blood pressure. Among them, Hmox1, Bdkrb2, Adra2b, Ptgs2, Col1a2 and Tbxa2r are associated with endothelium-derived hyperpolarizing factor (EDHF). NGS also identified genes in arachidonic acid metabolism (Cyp2c23, Hpgds, Ptgds and Ptges) that may be potential key genes/pathways contributing to renal programming and hypertension. Collectively, our NGS data suggest that maternal HF intake elicits a defective adaptation of interrelated EDHFs during nephrogenesis which may lead to renal programming and hypertension in later life. Moreover, our results highlight genes and pathways involved in renal programming as potential targets for therapeutic approaches to prevent metabolic-syndrome-related comorbidities in children with HF exposure in early life.

Albuminuria is an Independent Risk Factor of Erectile Dysfunction in Men with Type 2 Diabetes

INTRODUCTION Erectile dysfunction (ED) is a frequent comorbidity in men with diabetes and is frequently overlooked in routine clinical evaluation. Albuminuria, a marker of endothelial dysfunction, may link to ED. AIM The study evaluated the association of albuminuria with risk factors of ED in men with type 2 diabetes. METHODS The diagnosis of ED was based on a self-administered questionnaire containing Sexual Health Inventory for Men. Urinary albumin excretion rate was determined by urine albumin-to-creatinine ratio (UACR) in spot urine. MAIN OUTCOME MEASURES The clinical variables and diabetes-associated complications to risk of ED were evaluated. RESULTS Of 666 patients who received the questionnaire, 455 patients completed it. Among them, 82.0%, 28.1%, and 35.8% reported having ED, severe ED, and albuminuria, respectively. The UACR level was significantly higher in ED (0.20 ± 0.83) and severe ED (0.34 ± 1.18) groups compared with non-ED group (0.07 ± 0.33). The presence of albuminuria adjusted for age and duration of diabetes was significantly associated with ED (OR = 2.76), and macroalbuminuria has stronger impact (OR = 4.49) than microalbuminuria (OR = 2.48). The other associated risk factors included hypertension, higher level of systolic blood pressure, lower level of serum hemoglobin, and estimated glomerular filtration rate. The presence of retinopathy, neuropathy, insulin therapy, using calcium channel blocker, and higher level of HbA1c further correlated with severe ED. Men with severe ED have higher prevalence of subnormal testosterone than the no ED patients. The high sensitivity C-reactive protein level, and the presence of metabolic syndrome were not risk factors. The 211 nonrespondents to the questionnaire had similar or worse risk profiles compared with the ED patients. CONCLUSION Albuminuria is an important independent risk factor of ED in men with diabetes after adjustment of age and diabetes mellitus duration. Identification and control of albuminuria and other associated risk factors might play a role in the prevention or reversal of ED.

Functional and Molecular Characterization of Hyposensitive Underactive Bladder Tissue and Urine in Streptozotocin-Induced Diabetic Rat

Background The functional and molecular alterations of nerve growth factor (NGF) and Prostaglandin E2 (PGE2) and its receptors were studied in bladder and urine in streptozotocin (STZ)-induced diabetic rats. Methodology/Principal Findings Diabetes mellitus was induced with a single dose of 45 mg/kg STZ Intraperitoneally (i.p) in female Sprague-Dawley rats. Continuous cystometrogram were performed on control rats and STZ treated rats at week 4 or 12 under urethane anesthesia. Bladder was then harvested for histology, expression of EP receptors and NGF by western blotting, PGE2 levels by ELISA, and detection of apoptosis by TUNEL staining. In addition, 4-hr urine was collected from all groups for urine levels of PGE2, and NGF assay. DM induced progressive increase of bladder weight, urine production, intercontraction interval (ICI) and residual urine in a time dependent fashion. Upregulation of Prostaglandin E receptor (EP)1 and EP3 receptors and downregulation of NGF expression, increase in urine NGF and decrease levels of urine PGE2 at week 12 was observed. The decrease in ICI by intravesical instillation of PGE2 was by 51% in control rats and 31.4% in DM group at week 12. Conclusions/Significance DM induced hyposensitive underactive bladder which is characterized by increased inflammatory reaction, apoptosis, urine NGF levels, upregulation of EP1 and EP3 receptors and decreased bladder NGF and urine PGE2. The data suggest that EP3 receptor are potential targets in the treatment of diabetes induced underactive bladder.

The presence of overactive bladder wet increased the risk and severity of erectile dysfunction in men with type 2 diabetes.

INTRODUCTION Diabetes is a common risk factor for overactive bladder (OAB) syndrome and erectile dysfunction (ED). AIM The study evaluated the risk factors of OAB and association of OAB and ED in type 2 diabetic men. METHODS The diagnosis of ED and OAB was based on a self-administered questionnaire containing Sexual Health Inventory for Men (SHIM) and OAB symptom score (OABSS, 0-15, indicating increasing severity of symptoms), respectively. MAIN OUTCOME MEASURES The clinical variables and diabetes-associated complications, including ED, which are risk factors for OAB, were evaluated. RESULTS Of 453 consecutive subjects attending outpatient diabetic clinic with a mean age of 60.6 years, 25.4%, 10.2%, 81.9%, and 28.3% reported having OAB, OAB wet, ED, and severe ED, respectively. The OABSS is inversely associated with SHIM (correlation coefficient-0.275). The patients with OAB have significantly lower SHIM score, testosterone level, and serum albumin level, have more proportion of severe ED, were older, and have longer duration of diabetes mellitus (DM). After adjustment for age and duration of DM, the presence of severe ED was associated with OAB (odds ratio [OR] = 1.58), and severe ED (OR = 2.36), SHIM score (OR = 0.92), and serum albumin level (OR = 0.24) were risk factors for OAB wet (patients with urgency incontinence, once a week or more). The OR of ED in patients with OAB or OAB wet compared with no OAB was 1.82, and 3.61, respectively. Among the OAB components, urgency incontinence has the strongest impact on ED (OR = 4.06), followed by nocturia, urgency, and frequency. About 15.1% (N = 68) without OAB and ED are younger and have shorter DM duration, lower systolic BP, and higher serum albumin level after multivariate analysis compared with patients with OAB or ED. CONCLUSION The presence of severe ED was significantly associated with OAB, especially OAB wet. The presence of OAB wet increased the risk and severity of ED.

High-intensity diode laser in combination with bipolar transurethral resection of the prostate: A new strategy for the treatment of large prostates (>80 ml)†

The ideal treatment of large prostates with symptomatic benign prostatic hyperplasia (BPH) remains controversial. We compare the efficacy and safety of monopolar transurethral resection of the prostate (TURP) with high‐intensity diode laser in combination with bipolar TURP (DL + b‐TURP) in the treatment of large prostates.