High-affinity islet autoantibodies predict type 1 diabetes in mice and humans and implicate germinal centers (GCs) in type 1 diabetes pathogenesis. T follicular helper (Tfh) cells are increased in type 1 diabetic individuals and alterations in Tfh-like cells in the peripheral blood predicted individual responses to abatacept. Tfh cells support GC responses and depend on the transcriptional repressor BCL6 for their maturation. We therefore hypothesized that CD4-driven deletion of Bcl6 would disrupt essential T-B lymphocyte interactions in GCs to prevent type 1 diabetes. To test this hypothesis, we generated Bcl6fl/fl-CD4.Cre.NOD mice and found they were completely protected against diabetes. Insulitis severity and tertiary lymphoid structure organization were preserved in the pancreas of Bcl6fl/fl-CD4.Cre.NOD mice, which did not show decreases in CD4+, CD8+, and B cell numbers in the pancreas and draining lymph nodes, relative to control Bcl6fl/fl.NOD mice. CD4-driven loss of functional BCL6 resulted in significantly reduced GC B cell and Tfh cell numbers in the pancreatic lymph nodes and pancreas at late prediabetic intervals. Spontaneous anti-insulin autoantibody was blunted in Bcl6fl/fl-CD4.Cre.NOD mice. These data highlight BCL6 as a novel therapeutic target in type 1 diabetes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2337/db23-0709 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
"Now I can see it works!" Perspectives on Using a Nutrition-Focused Approach When Initiating Continuous Glucose Monitoring in People with Type 2 Diabetes: Qualitative Interview Study.
JMIR Diabetes
January 2025
Center for Evaluation and Survey Research, HealthPartners Institute, Bloomington, MN, United States.
Background: Food choices play a significant role in achieving glycemic goals and optimizing overall health for people with type 2 diabetes (T2D). Continuous glucose monitoring (CGM) can provide a comprehensive look at the impact of foods and other behaviors on glucose in real time and over the course of time. The impact of using a nutrition-focused approach (NFA) when initiating CGM in people with T2D is unknown.
View Article and Find Full Text PDFComparative efficacy and safety of sitagliptin or gliclazide combined with metformin in treatment-naive patients with type 2 diabetes: A single-center, prospective, randomized, controlled, noninferiority study with genetic polymorphism analysis.
Medicine (Baltimore)
January 2025
Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Background: This study evaluates the efficacy and safety of sitagliptin versus gliclazide, combined with metformin, in treatment-naive patients with type 2 diabetes mellitus (T2DM) and glucotoxicity.
Methods: In this single-center, randomized, controlled noninferiority trial, 129 treatment-naive patients with T2DM with glucotoxicity (fasting plasma glucose [FPG] ≥ 200 mg/dL and glycated hemoglobin ≥ 9.0%) were randomized to receive sitagliptin plus metformin (n = 66) or gliclazide plus metformin (n = 63) for 12 weeks.
Gitelman syndrome with diabetes and kidney stones: A case report.
Medicine (Baltimore)
January 2025
The Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou, China.
Rationale: Gitelman syndrome (GS) is a rare hereditary electrolyte disorder caused by mutations in the SLC12A3 gene. There is limited literature on the role of hydrochlorothiazide (HCT) testing and the SLC12A3 single heterozygous mutation in the diagnosis and management of patients with GS. In addition, cases of GS with concomitant kidney stones are rare.
View Article and Find Full Text PDFReduced circulating sphingolipids and activity are linked to T2D risk and impaired insulin secretion.
Sci Adv
January 2025
Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
Gestational diabetes mellitus (GDM), a transient form of diabetes that resolves postpartum, is a major risk factor for type 2 diabetes (T2D) in women. While the progression from GDM to T2D is not fully understood, it involves both genetic and environmental components. By integrating clinical, metabolomic, and genome-wide association study (GWAS) data, we identified associations between decreased sphingolipid biosynthesis and future T2D, in part through the allele of the gene in Hispanic women shortly after a GDM pregnancy.
View Article and Find Full Text PDFInfluence of Digital Health Literacy on Blood Pressure and Hemoglobin A1c in Patients With Comorbid Type 2 Diabetes and Hypertension.
Comput Inform Nurs
January 2025
Author Affiliations: Duke University School of Nursing (Drs Lee, Silva, Yang, Hatch, and Shaw and Mss Pennington, Matters, and Urlichich); and Duke University School of Medicine (Dr Crowley), Durham, NC.
Digital health literacy is emerging as an important element in chronic illness management, yet its relationship with clinical outcomes remains unclear. Utilizing data from the ongoing EXpanding Technology-Enabled, Nurse-Delivered Chronic Disease Care trial, this cross-sectional, correlational study explored the association between digital health literacy, health literacy, and patient outcomes, specifically blood pressure and hemoglobin A1c levels in 76 patients managing comorbid type 2 diabetes and hypertension. Results indicate patients had moderate digital health literacy, which was not significantly correlated with health literacy (r = 0.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!