Diabetic bladder dysfunction (DBD) is a common complication of diabetes with limited treatment options. While strict glucose regulation is theoretically beneficial, previous studies, like the Epidemiology of Diabetes Interventions and Complications study, suggest it may not reverse established dysfunction. This study evaluates whether early, strict glycemic control combined with NLRP3 inflammasome elimination can prevent DBD in female Akita mice, a Type 1 diabetes model. Female Akita mice exhibit overactive bladder (OAB) symptoms, driven by NLRP3-mediated inflammation. Using MRI-ultrasound (MRI-US) fusion imaging, researchers assessed the impact of glucose regulation and NLRP3 elimination on bladder function.
Female Akita mice, with NLRP3+/+ or NLRP3-/-, were subjected to varying glucose control levels starting at six weeks of age. Diabetic mice received insulin pellets for poor (0.05 U/day) or strict (0.125 U/day) glucose control, while bladder inflammation and urodynamics were analyzed at week 15. Blood glucose levels in the strictly controlled group (131±16 mg/dl) closely matched nondiabetics (113±5 mg/dl), while uncontrolled diabetics showed significantly higher levels (244±20 mg/dl). Poor glucose control reduced bladder inflammation and partially improved bladder overactivity, but strict control eliminated these issues entirely. Interestingly, NLRP3-/- mice, regardless of glucose levels, showed no bladder dysfunction, highlighting the critical role of NLRP3-induced inflammation.
These findings suggest that early and strict glycemic control, coupled with NLRP3 inhibition, effectively prevents DBD. The study underscores the potential of targeting NLRP3-mediated inflammation as an adjunct to glucose management. The integration of advanced imaging techniques, like ultrasound-guided urodynamics, enhances the accuracy of diagnosing and tracking bladder dysfunction, paving the way for innovative therapeutic strategies.
