MP59-07 STRICT GLUCOSE CONTROL AND ELIMINATION OF NLRP3-INDUCED INFLAMMATION PREVENTS DIABETIC BLADDER DYSFUNCTION IN THE FEMALE AKITA MOUSE MODEL
Bibliographic record
Abstract
You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology (MP59)1 May 2024MP59-07 STRICT GLUCOSE CONTROL AND ELIMINATION OF NLRP3-INDUCED INFLAMMATION PREVENTS DIABETIC BLADDER DYSFUNCTION IN THE FEMALE AKITA MOUSE MODEL Shelby N. Harper, Michael Odom, Francis M. Hughes, Huixia Jin, and Todd Purves Shelby N. HarperShelby N. Harper , Michael OdomMichael Odom , Francis M. HughesFrancis M. Hughes , Huixia JinHuixia Jin , and Todd PurvesTodd Purves View All Author Informationhttps://doi.org/10.1097/01.JU.0001009476.18935.3b.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Diabetic bladder dysfunction (DBD) is a prevalent complication with no specific treatment option. Logically, strict regulation of blood glucose should reverse dysfunction, but the Epidemiology of Diabetes Interventions and Complications study found strict control ineffective. However, it is possible that strict glucose control, initiated early, may prevent DBD. In this study, we examine the effect of early glucose control (strict and poor) on the development of DBD in the female Akita mouse, a Type 1 diabetic model. Female Akitas develop signs of overactive bladder (OAB) due to inflammation mediated by the NLRP3 inflammasome. Given the NLRP3-dependency of this model, we have expanded this study to evaluate eliminating NLRP3 as adjunct therapy to glucose control. METHODS: Akita mice were bred NLRP3+/+ or NLRP3-/-. Only females were used. At 6 weeks of age, diabetics received either no glucose control or insulin pellets (s.c., Linshin, Toronto) designed to poorly (0.05 U/day) or strictly (0.125 U/day) control blood glucose. At week 15, blood glucose (glucometer), HbA1c levels (ELISA), bladder inflammation (Evans blue) and bladder function (urodynamics) was assessed. RESULTS: Blood glucose (A) of uncontrolled diabetics was 244±20 mg/dl, which was reduced in the poorly controlled diabetics (186±13 mg/dl) and strongly reduced in the strictly controlled group (131±16 mg/dl). Nondiabetics averaged 113±5 mg/dl. These levels were not affected by deletion of NLRP3 and were reflected by HbA1c levels. Bladder inflammation (B) directly correlated with glucose control and was eliminated in the NLRP3-/- groups. Urodynamics found markers of overactivity (reduced void volume, etc.) in uncontrolled diabetics which improved in the poorly controlled group. Strict control eliminated dysfunction, showing that effective regulation of blood glucose, initiated early, can prevent DBD. In the NLRP3-/- mice, no bladder dysfunction developed. This suggests that elimination of NLRP3-induced inflammation will prevent DBD, an approach that may be an important adjunct to glucose control. CONCLUSIONS: Both early-initiated strict glycemic control and NLRP3 elimination can effectively prevent DBD, suggesting hyperglycemia acts through NLRP3-induced inflammation to trigger DBD. Download PPT Source of Funding: NIH-RO1 DK117890, NIH-K12 DK100024 © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e959 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Shelby N. Harper More articles by this author Michael Odom More articles by this author Francis M. Hughes More articles by this author Huixia Jin More articles by this author Todd Purves More articles by this author Expand All Advertisement PDF downloadLoading ...
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.041 | 0.007 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".