Diabetic Cystopathy Research Articles

Diabetic cystopathy due to detrusor muscle dysfunction in a child with type Ⅰ diabetes mellitus

Diabetic cystopathy due to detrusor muscle dysfunction in a child with type Ⅰ diabetes mellitus

Circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of diabetic cystopathy

Diabetic cystopathy (DCP) is a prevalent etiology of bladder dysfunction in individuals with longstanding diabetes, frequently leading to bladder interstitial fibrosis. Research investigating the initial pathological alterations of DCP is notably scarce. To comprehend the development of fibrosis and find effective biomarkers for its diagnosis, we prepared streptozotocin-induced long-term diabetic SD rats exhibiting a type 1 diabetes phenotype and bladder fibrosis in histology detection. After observing myofibroblast differentiation from rats’ primary bladder fibroblasts with immunofluorescence, we isolated fibroblasts derived exosomes and performed exosomal miRNA sequencing. The co-differentially expressed miRNAs (DEMis) (miR-16-5p and let-7e-5p) were screened through a joint analysis of diabetic rats and long-term patients’ plasma data (GES97123) downloaded from the GEO database. Then two co-DEMis were validated by quantitative PCR on exosomes derived from diabetic rats’ plasma. Following with a series of analysis, including target mRNAs and transcription factors (TFs) prediction, hubgenes identification, protein–protein interaction (PPI) network construction and gene enrichment analysis, a miRNA-mediated genetic regulatory network consisting of two miRNAs, nine TFs, and thirty target mRNAs were identified in relation to fibrotic processes. Thus, circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of DCP, and the crucial genes in regulatory network might hold immense significance in studying the pathogenesis and molecular mechanisms of fibrosis, which deserves further exploration.

Detection of antimicrobial susceptibility and virulence factors for some bacterial species caused urinary tract infection among type 1 and type 2 diabetes mellitus patients

Abstract Background: Diabetes mellitus (DM), is a metabolic illness caused by a deficiency in insulin production, action, or both, it is characterized by hyperglycemia and disruptions of the metabolism of carbohydrates, proteins, and fats. Urinary tracts infections (UTIs) are conditions when one or more urinary tract structures become contaminated after germs get past the body’s robust natural defenses. The most prevalent illness, UTIs can happen at any moment during a person’s lifetime. UTIs and DM have been linked for many years. Owing to a shift in the host defense mechanism, a micro-vascular illness in the kidney, and the existence of diabetic cystopathy, the incidence of UTIs is significant in DM. Urinary colonization by bacteria is made possible by high glucose concentrations in urine flow. Objective: Detection of antimicrobial susceptibility and virulence factors among bacteria causing UTIs isolated from type 1 and type 2 diabetic patients. Materials and Methods: Between April and July 2022, 178 patients with diabetes who had signs of a UTI had their urine samples taken. Midstream urine samples from DM patients were inoculated into blood agar and MacConkey agar using a calibrated loop (0.001 mL). For 24 h, cultures were incubated at 37°C in an aerobic environment. To determine whether there had been any considerable growth, colonies were counted. Diagnostic microorganisms were tested for their susceptibility to various antibiotics, and virulence factors were found. Results: Significant bacteriuria was observed in 28 of 69 (40.5%) and 52 of 109 (47.7%) urine samples cultured from patients with type 1 and 2 diabetes, respectively. Sensitivity to isolates which isolated from patients with type 1 and type 2 diabetes was highest for meropenem as 90% and 100%, respectively. With regard to virulence factor, it was investigated of biofilm formation, hemolysin production, protease production, urease production, and β-lactamase production. The highest ratio of these factors production in bacteria which isolated from patients with type 1 diabetes was β-lactamase (75.8%). As for patients with type 2 diabetes, the highest ratio was for biofilm formation (79.0%). Conclusion: According to this study, common antimicrobials are very resistant to many different drugs. UTIs are more common than previously thought, and type of diabetes was discovered to be one of the key contributing factors. We found an association between virulence factors of pathogens and type of diabetes.

Allograft inflammatory factor-1 enhances inflammation and oxidative stress via the NF-κB pathway of bladder urothelium in diabetic rat model

ObjectivesTo explore the role of allograft inflammatory factor-1 (AIF-1) both in diabetic rat bladder urothelium and in high-glucose-treated human urothelial cell line (SV-HUC-1). MethodsInflammation and oxidative stress (OS) promote diabetic cystopathy (DCP), but the mechanisms are not fully understood. The expression level of AIF-1 in diabetic rat bladder urothelium and in the SV-HUC-1 cells treated with high glucose was detected using tissue immunofluorescence, immunohistochemistry and western blot assays. AIF-1 was knocked down and NF-κB was suppressed with the specific inhibitor BAY 11–7082 in high-glucose-treated SV-HUC-1 cells. ResultsHigh-glucose condition induced AIF-1 upregulation in vivo and in vitro. The up-regulated AIF-1 induced the production of inflammatory factors IL-6 and TNF-α and elevation of ROS. Informatics analysis suggested that NF-κB pathway is implicated in DCP. Through knockdown of AIF-1, we confirmed that AIF-1 simulated NF-κB pathway by enhancing the phosphorylation of IκB (p-IκB) and promoting the translocation of NF-κB p65 from cytoplasm into nucleus. Additionally, High-glucose-induced inflammation in SV-HUC-1 cells was attenuated by the addition of NF-κB inhibitor. ConclusionsThis study provides novel information to understand the molecular regulation mechanisms of AIF-1 in DCP.

Differentially Expressed mRNA in Streptozotocin-Induced Diabetic Bladder Using RNA Sequencing Analysis.

To detect elements governing the pathogenesis of diabetic cystopathy (DC), mRNA sequencing was carried out for bladder tissues from normal rats and those with induced diabetes mellitus (DM). This research therefore offers possible underlying molecular pathways for the advancement of DC in relation to differential mRNA expression, together with visceral functional and architectural alterations noted in individuals with this condition. An intraperitoneal injection of streptozotocin (STZ) was utilized to provoke DM in male Sprague-Dawley rats. Dysregulation and significant variations between normal rats and those with induced DM were then identified by a fold change of ≥ 1.5 with a false discovery rate P < 0.05. Hierarchical clustering/heat map and Gene Ontology/DAVID reference sources were generated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction analysis were then performed. The diabetic rodent group exhibited a greater residual urine volume (4.0 ± 0.4 mL) than their control counterparts (0.7 ± 0.2 mL, P < 0.01) at 12 weeks after diagnosis of diabetes. Expression analysis revealed 16 upregulated and 4 downregulated genes in STZDM bladder samples. A notable increase in expression was seen in PTHLH, TNFAIP6, PRC1, MAPK10, LOC686120, CASQ2, ACTG2, PDLIM3, FCHSD1, DBN1, NKD2, PDLIM7, ATF4, RBPMS2, ITGB1 and HSPB8. A notable decrease in expression was seen in SREBLF1, PBGFR1, PBLD1 and CELF1. Major genetic themes associated with mRNA upregulation and downregulation ware identified via Gene Ontology analysis and KEGG pathways. Protein to protein interaction analysis detected PDLIM3, PDLIM7, ITGB1, ACTG2 as core high frequency nodes within the network. Changes in mRNA expression together with biological process and pathways that contribute to the etiologies underlying visceral impairment of the bladder in DM are evident. Our strategy is promising for recognizing mRNAs exclusive to the bladder in DM that might offer useful targets for diagnosis and treatment.

Long-term aspirin administration suppresses inflammation in diabetic cystopathy.

Diabetic cystopathy (DCP) is one of the most common and troublesome urologic complications of diabetes mellitus, characterized by chronic low-grade inflammatory response. However, the correlation between inflammation and disease progression remains ambiguous and effective drugs interventions remain deficient. Herein, during 12-week study, 48 male Sprague-Dawley rats were randomly assigned to four groups: negative control (NC), NC treated with aspirin (NC+Aspirin), DCP, and DCP treated with aspirin (DCP+Aspirin). Type 1 diabetes mellitus was established by intraperitoneal injection of streptozotocin (65 mg/kg). After 2 weeks modeling, the rats in treatment groups received daily oral aspirin (100 mg/kg/d). After 10 weeks of treatment, aspirin ameliorated pathological weight loss and bladder weight increase in diabetic rats, accompanied by a 16.5% decrease in blood glucose concentrations. H&E, Masson, immunohistochemistry and transmission electron microscopy revealed that a dilated bladder with thickened detrusor smooth muscle (DSM) layer, inflammatory infiltration, fibrosis and ultrastructural damage were observed in diabetic rats, which were obviously ameliorated by aspirin. The dynamic investigations at 4, 7 and 10 weeks revealed inflammation gradually increased as the disease progresses. After 10 weeks of treatment, the expression of TNF-α, IL-1β, IL-6, and NF-κB has been decreased to 78%, 39.7%, 44.1%, 33.3% at mRNA level and 67.6%, 76.7%, 71.4%, 67.1% at protein level, respectively (DCP+Aspirin vs. DCP, p < 0.01). Aspirin partially restored the increased expression of inflammatory mediators in bladder DSM of diabetic rats. The study provided insight into long-term medication therapies, indicating that aspirin might serve as a potential strategy for DCP treatment.

STRUCTURE OF INTRAMURAL NERVE ELEMENTS OF THE URINARY BLADDER IN PATIENTS WITH DIABETIC CYSTOPATHY

Using histological, and histochemical methods, morphological changes in the intramural nerve elements of the urinary bladder were studied in 6 patients suffering from diabetic cystopathy and who died from various complications of diabetes mellitus. The control group consisted of 4 practically healthy persons who died as a result of a car accident. For histological examination, tissue pieces of the nerve elements of the bladder were fixed with 12% formalin and impregnated according to the method of Bilshchovsky-Gross and Rasskazov. Adrenergic nerve structures were detected by incubation of sections in a 2% solution of glyoxylic acid, and cholinergic elements by the Karnovsky-Roots method. It was revealed that along with degenerative changes, reactive-compensatory processes also occur in the intramural nerve elements of the bladder in diabetic cystopathy. It was found that the activity of mediators in adrenergic and cholinergic structures decreases.

REPRODUCTIVE HORMONE LEVELS IN WOMEN WITH THALASSEMIA

Using histological, and histochemical methods, morphological changes in the intramural nerve elements of the urinary bladder were studied in 6 patients suffering from diabetic cystopathy and who died from various complications of diabetes mellitus. The control group consisted of 4 practically healthy persons who died as a result of a car accident. For histological examination, tissue pieces of the nerve elements of the bladder were fixed with 12% formalin and impregnated according to the method of Bilshchovsky-Gross and Rasskazov. Adrenergic nerve structures were detected by incubation of sections in a 2% solution of glyoxylic acid, and cholinergic elements by the Karnovsky-Roots method. It was revealed that along with degenerative changes, reactive-compensatory processes also occur in the intramural nerve elements of the bladder in diabetic cystopathy. It was found that the activity of mediators in adrenergic and cholinergic structures decreases.

Distended Bladder beyond the Umbilicus: Asymptomatic Diabetic Cystopathy.

Distended Bladder beyond the Umbilicus: Asymptomatic Diabetic Cystopathy.

Therapeutic effects of silodosin and urapidil on underactive bladder associated with diabetic cystopathy.

Pharmacological treatment options for underactive bladder (UAB) syndrome are limited. Urapidil is the only alpha1 -adrenoceptor (AR) antagonist that can be used for urinary disorders in women in some countries. However, no studies have directly verified the effects of alpha1 -AR antagonists on the female urethra and UAB-like dysfunctions. We investigated the effects of silodosin (alpha1A -AR antagonist) and urapidil (nonselective alpha1 -AR antagonist) on the voiding function in female rats with diabetes mellitus (DM). Changes in intraurethral pressure (IUP) induced by midodrine (alpha1 -AR agonist) and mean blood pressure (MBP) were continuously measured in normal female rats to verify the pharmacological profiles of the drugs. To establish a DM model, rats were administered streptozotocin (STZ; 50 mg/kg, intravenous). Eight weeks after STZ administration, drugs were subcutaneously delivered through an osmotic pump. Four weeks after drug administration, emptied bladder blood flow (BBF), intravesical pressure, and the micturition volume were measured. Both silodosin and urapidil inhibited the midodrine-induced increase in IUP and decreased MBP in a dose-dependent manner. Silodosin had a more substantial effect on the lower urinary tract than on MBP. Twelve weeks after STZ administration, DM rats exhibited UAB-like dysfunction (increased bladder capacity/bladder weight and residual volume and decreased bladder voided efficiency) and decreased BBF. Both drug treatments controlled this dysfunction. Alpha1 -AR antagonists induced dose-dependent urethral relaxation in female rats. These drugs ameliorated UAB-like dysfunction in STZ-induced DM rats. In addition, alpha1A -AR antagonists such as silodosin, which have limited effects on blood pressure, appear to be useful for treating UAB.

Anti-inflammation properties of resveratrol in the detrusor smooth muscle of the diabetic rat.

In this paper, we aimed to prove that resveratrol can inhibit inflammation in the detrusor smooth muscle of diabetic rats, which may provide a new direction for diabetic cystopathy (DCP) treatment. We induced a Sprague-Dawley (SD) rat model of type 1 diabetes by intraperitoneal injections of streptozotocin (STZ). Then, we separated the SD rats into four groups: (1) an excipient-treated control group; (2) a resveratrol-treated control group; (3) an excipient-treated streptozotocin (STZ)-injected group; and (4) a resveratrol-treated STZ-injected group. We administered the resveratrol or excipient by intragastric administration. After 12weeks of diabetes induction, we measured the blood-sugar concentrations and bladder weights, and we took the bladder tissues of each group of rats for hematoxylin-eosin staining to observe the histological changes. We used real-time quantitative polymerase chain reaction (qPCR) and Western blotting to analyze the expression levels of tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), interleukin (IL)-6, and IL-1β. The bodyweights of the diabetic rats were appreciably reduced, while the bladder weights and blood-glucose concentrations were substantially increased. Oral resveratrol could not improve the changes in the bodyweights and blood-glucose concentrations, but it had a certain effect on the bladder weights. In a macroscopic evaluation, the bladder walls of the STZ-induced diabetes rats were thickened, and, from the H&E staining, we could see that the bladder tissues of the diabetic rats had inflammatory cell infiltration, edema, and the capillary congestion of the mucosa and lamina propria. After resveratrol treatment, the bladder-wall thickening was reduced, and the tissue damage and inflammation were significantly ameliorated. We could associate all these changes with markedly heightened expressions of TNF-α, IL-1β, IL-6, and NF-κB in the detrusor smooth muscle (DSM) tissues of the diabetic rats. Oral treatment with resveratrol alleviated the expressivity of the inflammatory cytokines in the DSM tissues. Resveratrol treatment ameliorated the histological changes in the bladder and inhibited the expressions of DSM-tissue inflammatory factors in diabetes rats. Resveratrol may provide a new direction of research for the treatment of diabetic cystopathy.

The incidence of Diabetic Cystopathy among Iraqi Diabetic Patients with lower Urinary Tract Symptoms

Background: Diabetic cystopathy disease is one of the most important problems facing diabetics. Determining theprevalence rate is one of the basics to know the effect of hyperglycemia on bladder patients to provide them withthe best treatment services. And reduce the percentage of damage that occurs to the functioning of the bladderover a duration of disease.Aim of study: identify the prevalence of diabetic cystopathy among diabetic patients.Patients and methods: A cross sectional study were conducted from the first of Jun 2019 to end of December 2020.We selected convenient sample includes all Diabetic patients presenting with voiding dysfunction attending toprivate clinic of Dr. Saif al-haideri for urodynamic study and and who that meeting the eligibility criteria, datacollection by A structured questionnaire is developed to collect information from the participation after physicalexamination and Urodynamic evaluation was done.Result: The total study sample were 550 diabetic patients, out of them 112 (20.4%) were diabetic cystopathy.(56% male and 44% female) with mean age was 56.50±15.50 years. The mean duration of diabetic diagnosis was(13.7±8.25) years with 75% were more than 10 years, while (742.70±158.29 ml) the mean volume of bladder capacityand (87.35±81.82 ml/cm H2O) mean of compliance and without any statically significant association (p=0.120 and0.989 respectively).Conclusion: 20.4% of Iraqi diabetic patients have diabetic cystopathy, and without any statically significantassociation between urodynamic finding and duration of diabetic disease.

The effect of type 2 diabetes mellitus (DM) on bladder contractility in diabetic men

Aims: To clarify the effect of DM type 2 on bladder contractility in type 2 diabetic patients. Methods: Patients (60 adult male patients) with lower urinary tract symptoms (LUTS) underwent a detailed urodynamic investigation. Urodynamic findings were classified as diabetic cystopathy [DC, characterized by impaired bladder sensation, increased post-void residual urine (PVR) and increased bladder capacity and decreased bladder contractility], detrusor overactivity. Results: All the patients in the diabetic group had type 2 diabetes mellitus for average 14 years and only 9/60 patients(15% of the diabetic group) has weak detrusor contractility their BCI less than 100. The rest of diabetic group 51/60 (85%) had good detrusor contractility. This means that diabetes (even with long duration&gt;10 years) does not affect the detrusor contractility in our diabetic patients. 30 patients of the group (50%) had increased cystometric capacity (&gt;450 CC),12 patients (20%) had reduced cystometric capacity (&lt;250CC) while the rest of the patients(18 patients i.e. 30%) had average cystometric capacity(300 :450CC). 30 patients of the group (50%) had increased post voiding residual urine volume (PVR)(PVR up to 500 CC),while 30 patients of the group (50%)had normal PVR(&lt;100CC).

Daidzein attenuates urinary bladder dysfunction in streptozotocin-induced diabetes in rats by NOX-4 and RAC-1 inhibition.

Reactive oxygen species via NADPH oxidase (NOX) activation are involved in the pathogenesis of many disease conditions such as diabetes and its complications. In the present study, we have examined the effect of daidzein in the management of diabetic cystopathy. Diabetes was induced in male Sprague Dawley rats via intraperitoneal injection of streptozotocin (STZ) at a dose of 55mg/kg. After 6weeks of diabetes induction, animals were treated with daidzein orally at a dose of 25, 50, and 100mg/kg for 4weeks. Diabetic animals showed increase (p < 0.001) in bladder capacity (4.32 ± 0.43mL) and residual volume (2.53 ± 0.19mL) when compared with normal control animals (2.10 ± 0.40mL and 0.51 ± 0.12mL res). Treatment with daidzein at dose of 50 and 100mg/kg significantly reduced the elevated bladder capacity (2.91 ± 0.11mL, p < 0.01 and 2.65 ± 1.13mL, p < 0.001) and residual volume (1.40 ± 0.15mL, p < 0.001 and 1.15 ± 0.05mL, p < 0.001). Daidzein-treated animals also showed improvement in voiding efficiency. Elevated threshold and baseline pressure were also found to be reduced in diabetic animals after 4weeks of daidzein treatment. Daidzein treatment also prevented the loss of antioxidant enzymes in the urinary bladder and also reduced the expression of NOX-4 and RAC-1 in the bladder. From the results, it can be concluded that daidzein showed a beneficial effect on urinary bladder dysfunction in diabetic animals.

Diabetic cystopathy preceding renal microabscess with papillary necrosis.

Diabetic cystopathy preceding renal microabscess with papillary necrosis.

Lower urinary tract dysfunction in diabetes mellitus: the forgotten disease

Diabetic cystopathy is a common complication in patients with diabetes mellitus. It may cause a variety of manifestations ranging from bladder hyperactivity to decreased bladder contractibility. However, the presence of bladder dysfunction in diabetic patients is often underdiagnosed by clinicians. We present a case report of a 54-year-old woman with a medical history of diabetes with recurrent lower urinary tract infections and pyelonephritis. Her bladder dysfunction was never assessed until she was admitted to our department. We identified an impaired sensation of bladder filling and an inability to voluntarily contract the detrusor. We provided pharmacological treatment to enhance bladder emptying and proposed a new bladder-emptying regimen. The patient remains with this therapeutic strategy with no evidence of further complications. This case aims to raise awareness among clinicians about diabetic bladder dysfunction.

Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder

Diabetes mellitus (DM) is the leading cause of chronic kidney disease and diabetic nephropathy is widely studied. In contrast, the pathobiology of diabetic urinary bladder disease is less understood despite dysfunctional voiding being common in DM. We hypothesised that diabetic cystopathy has a characteristic molecular signature. We therefore studied bladders of hyperglycaemic and polyuric rats with streptozotocin (STZ)-induced DM. Sixteen weeks after induction of DM, as assessed by RNA arrays, wide-ranging changes of gene expression occurred in DM bladders over and above those induced in bladders of non-hyperglycaemic rats with sucrose-induced polyuria. The altered transcripts included those coding for extracellular matrix regulators and neural molecules. Changes in key genes deregulated in DM rat bladders were also detected in db/db mouse bladders. In DM rat bladders there was reduced birefringent collagen between detrusor muscle bundles, and atomic force microscopy showed a significant reduction in tissue stiffness; neither change was found in bladders of sucrose-treated rats. Thus, altered extracellular matrix with reduced tissue rigidity may contribute to voiding dysfunction in people with long-term DM. These results serve as an informative stepping stone towards understanding the complex pathobiology of diabetic cystopathy.

50week ultrasound imaging and ultrastructural abnormalities of bladder after sugar diuresis and diabetes mellitus in rats.

PurposeTo investigate 50 week ultrasound imaging and ultrastructure changes of bladder in diuresis and diabetes rats.MethodsForty-two healthy male Sprague–Dawley rats were randomly divided into control group, sugar-induced diuresis group and streptozotocin-induced diabetes group. The 24 h drinking and urine volume were calculated from 21 to 31 weeks. Using ultrasound to assess bladders after 49 weeks. Bladders were examined by transmission electron microscope after 50 weeks.ResultsThe drinking and urine volume significantly increased in the diuresis and diabetes groups. The bladder morphology and bladder wall thickness increased in the diuresis and diabetes groups. Bladder stones, bladder overdistension and urinary retention were seen in the diuresis and diabetes groups. Urothelium manifested degeneration, denudation and necrosis in the diuresis and diabetes groups. The mitochondrial vacuolar degeneration in the urothelial cells was seen in the diabetes group. The subepithelial vascular endothelial cells hyperplasia with a narrowed lumen were observed in the diabetes group. Abnormal mitochondria were rarely seen in the control group. The mitochondrial vacuolar degeneration in the detrusor was more severe in the diabetes group than in the diuresis group. The detrusor muscle and axon degeneration were observed in the diuresis and diabetes groups. Two rats in the diuresis group share similarities with diabetes group (2/6).ConclusionLong-term diabetes mellitus can cause increments of urinary bladder morphology and bladder wall thickness, urinary retention and bladder stones. Ultrastructural degeneration of the bladder might be the morphological bases of diabetic cystopathy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11255-021-02911-w.

Abstract #999711: The Burden of A Complication without Too Many Alternatives, Diabetic Cystopathy

Abstract #999711: The Burden of A Complication without Too Many Alternatives, Diabetic Cystopathy

The current paradigm of diabetic cystopathy in Mexico

The term diabetic cystopathy describes the increase in bladder capacity and post-void residual volumes in diabetic patients, accompanied by decreased bladder sensation and contraction, attributed to diabetic neuropathy. Diabetic cystopathy is mainly one originated by a neuropathy, of sensory and autonomic origin due to the alterations suffered in the nerve fibers; in this article we will review the multiple theories about physiopathology. Patients present with an insidious symptomatology and when it is detectable is in an advanced stage, the main symptom is urinary incontinence. Its diagnosis is established through clinical presentation associated with neurological symptoms and confirmed by urodynamic studies. Strict control and adherence to DM2 treatment is the cornerstone to avoid long-term complications, including "Diabetic Cystopathy". If the disease is already established, pharmacological treatment is indicated, with a wide range of drugs to choose from; if it is not a candidate for pharmacological therapy or has severe symptoms, surgical management is possible with several surgical options such as bladder denervation or myomectomy.