The Role Of Polyuria And Hyperglycemia In Diabetic Bladder Dysfunction

Purpose:Diabetic bladder dysfunction (DBD), a collective description of clinical symptoms including decreased sensation, increased capacity, poor emptying, and also detrusor overactivity, is among the most common and costly complications of diabetes mellitus (DM). It is estimated that DBD occurs in approximately87%of individuals diagnosed with DM. and substantially affects quality of life. Yet. little is known about the pathogenic mechanisms of DBD. Unlike other organs, the bladder experiences not only hyperglycemia, but also an increased volume of urine in DM. To aid in our knowledge of the pathophysiology of DBD and to aid development of specific treatments, identification of individual contributions of polyuria and hyperglycemia in the DBD is essential.Materials and Methods:Seventy two female Sprague-Dawley rats were divided into6groups: age-matched controls (control), sham urinary diversion (sham), urinary diversion (UD), streptozotocin-induced diabetics after sham urinary diversion (DM), streptozotocin-induced diabetics after urinary diversion (UD+DM), and5%sucrose-induced diuretics after sham urinary diversion (DIU). UD was performed10days before diabetes induction by surgical disconnection of the ureters from the bladder and implantation to uterine cervix. Each group was subsequently evaluated20weeks after diabetes or diuresis induction. Twenty-four hour drinking and voided volumes were measured. Conscious cystometry (CMG) was examined. The bladders were harvested for histological examination and quantification of smooth muscle, urothelium, and collagen. We measured the expressions of oxidative stress-related proteins, nitrotyrosine and manganese superoxide dismutase (MnSOD), in bladder.Results:Diabetes and diuresis caused increases in drinking volume, voiding volume and bladder weight. Bladder weights decreased in the UD and UD+DM groups. Intercontractile intervals, voided volume, and compliance increased in the DIU and DM groups, decreased in the UD, and further decreased in the UD+DM group. The total cross-sectional tissue, smooth muscle and urothelium areas increased in the DIU and DM groups, and decreased in the UD and UD+DM groups. As percentages of total tissue area, collagen decreased in the DIU and DM groups, and increased in the UD and UD+DM groups, and smooth muscle and urothelium decreased in the UD and UD+DM groups. Nitrotyrosine and MnSOD increased in DM and UD+DM rats.Conclusions:The urinary diversion animal model is feasible for DBD research. Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial oxidative stress in the bladder, which may play a pathogenic role in late stage DBD.