Background: Urinary bladder dysfunction is a major complication of diabetes mellitus and its mechanism has been attributed to autonomic and/or peripheral neuropathy. Objectives: Evaluation of diabetes mellitus and neu...Background: Urinary bladder dysfunction is a major complication of diabetes mellitus and its mechanism has been attributed to autonomic and/or peripheral neuropathy. Objectives: Evaluation of diabetes mellitus and neuropathy effect on the urinary bladder dynamics in children and adolescents with Type 1 diabetes mellitus. Patients and Methods: The study included 80 children and adolescents with Type 1 diabetes for at least 5 years;60 patients were with manifestations of autonomic and/or peripheral neuropathy and 20 patients were free of either. We assessed both groups for presence of cystopathy by means of uroflowmetry and cystometry. Results: All patients with diabetic neuropathy had abnormal urodynamic test results of variable types and degrees with bladder hypercompliance as the most frequent abnormality. Other urodynamic abnormalities were found in both diabetic patients’ groups with no significant difference in frequency. Conclusions: Diabetic neuropathy might be strongly related to urodynamic abnormalities particularly the bladder hypercompliance. Some diabetic patients may have cystopathy in absence of evident neuropathy. This may be due to undetected neuropathy or diabetes induced myopathy of the detrusor muscle.展开更多
BACKGROUND Diabetic cystopathy(DCP)is a complication affecting the lives of people with diabetes.However,the pathogenesis of DCP is not well known.AIM To investigate the potential mechanisms by which cAMP-responsive e...BACKGROUND Diabetic cystopathy(DCP)is a complication affecting the lives of people with diabetes.However,the pathogenesis of DCP is not well known.AIM To investigate the potential mechanisms by which cAMP-responsive elementbinding protein 3 like 3(CREB3 L3)promotes the occurrence and development of DCP.METHODS High-throughput sequencing was used to analyze differentially expressed genes(DEGs)in bladder urothelium from patients with DCP and healthy controls.Gene enrichment analysis was conducted to assess the biological functions of DEG.Small interfering RNA technology was performed to silence the CREB3 L3 gene in both in vitro and in vivo experiments.Morphological changes in bladder urothelium from a DCP rat model were observed.Immunofluorescence and western blotting assay were performed to determine associated protein expression.RESULTS We identified significant DEGs through high-throughput sequencing.These genes were primarily enriched in inflammatory activation,epithelial-mesenchymal transition(EMT)and tight junction organization.Upregulated expression of both CREB3 L3 and C-reactive protein(CRP)in bladder urothelium from patients with DCP was accompanied by upregulated EMT markers including N-cadherin and vimentin proteins,but downregulated E-cadherin.Silencing CREB3 L3 attenuated the protein expression of CRP and EMT in SV-HUC-1 urothelial cells under hyperglycemic conditions and in the diabetes mellitus rat model at 4,8,and 12 weeks.CREB3 L3 knockdown also reversed downregulation of the tight junction proteins occludin and claudin 1.CONCLUSION Hyperglycemia induces the upregulation of CREB3 L3 expression,thereby promoting the EMT and impairing tight junctions in bladder urothelial cells.Targeting CREB3 L3 in bladder urothelial cells is likely to be a key approach in preventing and treating DCP.展开更多
Objective To review studies on diabetic bladder dysfunction （DBD）,a common and bothersome complication of diabetes mellitus.Data sources We performed a search of the English literature through PubMed.The key words u...Objective To review studies on diabetic bladder dysfunction （DBD）,a common and bothersome complication of diabetes mellitus.Data sources We performed a search of the English literature through PubMed.The key words used were ＂diabetes＂ and ＂bladder dysfunction＂ or ＂cystopathy＂.Our own data and perspective are included in the discussion.Study selection Studies containing data relevant to DBD were selected.Because of the limited length of this article,we also referenced reviews that contain comprehensive amalgamations of relevant literature.Results The classic symptoms of DBD are decreased bladder sensation,increased bladder capacity,and impaired bladder emptying with resultant elevated post-void residual urine.However,recent clinical and experimental evidence indicate a strong presence of storage problems such as urge incontinence in diabetes.Recent studies of DBD in animal models of type 1 diabetes have revealed temporal effects of diabetes,causing an early phase of compensatory bladder function and a later phase of decompensated bladder function.The pathophysiology of DBD is multifactorial,including disturbances of the detrusor,urothelium,autonomic nerves,and urethra.Polyuria and hyperglycemia play important but distinctive roles in induction of bladder dysfunction in type 1 diabetes.Polyuria causes significant bladder hypertrophy in the early stage of diabetes,whereas oxidative stress in the bladder caused by chronic hyperglycemia may play an important role in the late stage failure of bladder function.Conclusions DBD includes time-dependent and mixed manifestations.The pathological alterations include muscle,nerve,and urothelium.Polyuria and hyperglycemia independently contribute to the pathogenesis of DBD.Treatments for DBD are limited.Future clinical studies on DBD in type 1 and type 2 diabetes should be investigated separately.Animal studies of DBD in type 2 diabetes are needed,from the natural history to mechanisms.Further understanding of the molecular mechanisms of DBD will provide multiple potential targets for therapeutic intervention.展开更多
文摘Background: Urinary bladder dysfunction is a major complication of diabetes mellitus and its mechanism has been attributed to autonomic and/or peripheral neuropathy. Objectives: Evaluation of diabetes mellitus and neuropathy effect on the urinary bladder dynamics in children and adolescents with Type 1 diabetes mellitus. Patients and Methods: The study included 80 children and adolescents with Type 1 diabetes for at least 5 years;60 patients were with manifestations of autonomic and/or peripheral neuropathy and 20 patients were free of either. We assessed both groups for presence of cystopathy by means of uroflowmetry and cystometry. Results: All patients with diabetic neuropathy had abnormal urodynamic test results of variable types and degrees with bladder hypercompliance as the most frequent abnormality. Other urodynamic abnormalities were found in both diabetic patients’ groups with no significant difference in frequency. Conclusions: Diabetic neuropathy might be strongly related to urodynamic abnormalities particularly the bladder hypercompliance. Some diabetic patients may have cystopathy in absence of evident neuropathy. This may be due to undetected neuropathy or diabetes induced myopathy of the detrusor muscle.
基金Supported by Guangxi Natural Science Foundation,No.2024GXNSFAA010031.
文摘BACKGROUND Diabetic cystopathy(DCP)is a complication affecting the lives of people with diabetes.However,the pathogenesis of DCP is not well known.AIM To investigate the potential mechanisms by which cAMP-responsive elementbinding protein 3 like 3(CREB3 L3)promotes the occurrence and development of DCP.METHODS High-throughput sequencing was used to analyze differentially expressed genes(DEGs)in bladder urothelium from patients with DCP and healthy controls.Gene enrichment analysis was conducted to assess the biological functions of DEG.Small interfering RNA technology was performed to silence the CREB3 L3 gene in both in vitro and in vivo experiments.Morphological changes in bladder urothelium from a DCP rat model were observed.Immunofluorescence and western blotting assay were performed to determine associated protein expression.RESULTS We identified significant DEGs through high-throughput sequencing.These genes were primarily enriched in inflammatory activation,epithelial-mesenchymal transition(EMT)and tight junction organization.Upregulated expression of both CREB3 L3 and C-reactive protein(CRP)in bladder urothelium from patients with DCP was accompanied by upregulated EMT markers including N-cadherin and vimentin proteins,but downregulated E-cadherin.Silencing CREB3 L3 attenuated the protein expression of CRP and EMT in SV-HUC-1 urothelial cells under hyperglycemic conditions and in the diabetes mellitus rat model at 4,8,and 12 weeks.CREB3 L3 knockdown also reversed downregulation of the tight junction proteins occludin and claudin 1.CONCLUSION Hyperglycemia induces the upregulation of CREB3 L3 expression,thereby promoting the EMT and impairing tight junctions in bladder urothelial cells.Targeting CREB3 L3 in bladder urothelial cells is likely to be a key approach in preventing and treating DCP.
文摘Objective To review studies on diabetic bladder dysfunction （DBD）,a common and bothersome complication of diabetes mellitus.Data sources We performed a search of the English literature through PubMed.The key words used were ＂diabetes＂ and ＂bladder dysfunction＂ or ＂cystopathy＂.Our own data and perspective are included in the discussion.Study selection Studies containing data relevant to DBD were selected.Because of the limited length of this article,we also referenced reviews that contain comprehensive amalgamations of relevant literature.Results The classic symptoms of DBD are decreased bladder sensation,increased bladder capacity,and impaired bladder emptying with resultant elevated post-void residual urine.However,recent clinical and experimental evidence indicate a strong presence of storage problems such as urge incontinence in diabetes.Recent studies of DBD in animal models of type 1 diabetes have revealed temporal effects of diabetes,causing an early phase of compensatory bladder function and a later phase of decompensated bladder function.The pathophysiology of DBD is multifactorial,including disturbances of the detrusor,urothelium,autonomic nerves,and urethra.Polyuria and hyperglycemia play important but distinctive roles in induction of bladder dysfunction in type 1 diabetes.Polyuria causes significant bladder hypertrophy in the early stage of diabetes,whereas oxidative stress in the bladder caused by chronic hyperglycemia may play an important role in the late stage failure of bladder function.Conclusions DBD includes time-dependent and mixed manifestations.The pathological alterations include muscle,nerve,and urothelium.Polyuria and hyperglycemia independently contribute to the pathogenesis of DBD.Treatments for DBD are limited.Future clinical studies on DBD in type 1 and type 2 diabetes should be investigated separately.Animal studies of DBD in type 2 diabetes are needed,from the natural history to mechanisms.Further understanding of the molecular mechanisms of DBD will provide multiple potential targets for therapeutic intervention.
