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Markers Predicting Cure With Combinatorial Treatment in a Mouse Model of Latent Autoimmune Diabetes in Adults
Wisal Sawaed1, Ahmad Dallasheh1, Sivan Eliyahu1
1The Regenerative Medicine and Diabetes Laboratory The Azrieli Faculty of Medicine Bar-Ilan University Safed Israel.
Abstract:
Diabetes encompasses a range of diseases characterized by chronic hyperglycemia and serious health complications. However, predicting therapeutic response in latent autoimmune diabetes in adults (LADA) remains a major challenge, limiting the development of personalized treatment strategies. LADA is a relatively newly defined diabetes type that shares features of Type 1 diabetes (T1D) and Type 2 diabetes and is estimated to be more prevalent than T1D. We developed a LADA model in NOD mice and assessed combination treatment (CT) comprising GABA, sitagliptin, and omeprazole. Surprisingly, ∼30% of the CT-treated mice completely recovered, exhibiting normoglycemia and insulin independence. We identified two cell-free RNA markers, Adgrb1 and Chd5, that distinguish responders from nonresponders, indicating promising predictive ability. These discoveries offer a potential diagnostic tool for identifying LADA patients who could benefit from CT, representing an advance in personalized diabetes treatment. CT-induced β-cell neogenesis involved replication, providing valuable insights into β-cell regeneration mechanisms. Furthermore, the cured mice exhibited insulitis primarily populated by T regulatory Type 1 cells, potentially suppressing autoimmunity and facilitating β-cell survival and regeneration. This study opens new avenues for targeted LADA therapies and paves the way for precision medicine in diabetes management.
Insights
Researchers identified potential biomarkers (Adgrb1 and Chd5) to predict treatment response in latent autoimmune diabetes in adults (LADA). A combination therapy (CT) surprisingly led to remission in 30% of mice, offering hope for personalized diabetes care.
Area of Science:
- Immunology
- Endocrinology
- Genetics
Background:
- Latent autoimmune diabetes in adults (LADA) presents a diagnostic and therapeutic challenge due to its hybrid features of Type 1 and Type 2 diabetes.
- Predicting treatment response in LADA is crucial for developing personalized medicine strategies.
Purpose of the Study:
- To develop a LADA mouse model and evaluate a combination therapy (CT) comprising GABA, sitagliptin, and omeprazole.
- To identify biomarkers for predicting therapeutic response in LADA.
Main Methods:
- Development of a LADA model in NOD mice.
- Administration of a combination therapy (CT) including GABA, sitagliptin, and omeprazole.
- Identification of cell-free RNA markers (Adgrb1 and Chd5) to distinguish responders from nonresponders.
Main Results:
- Approximately 30% of CT-treated mice achieved complete remission, characterized by normoglycemia and insulin independence.
- Adgrb1 and Chd5 were identified as predictive markers for treatment response.
- CT induced beta-cell neogenesis and regeneration, with 'cured' mice showing insulitis populated by T regulatory Type 1 cells.
Conclusions:
- The study presents a promising combination therapy and predictive biomarkers for LADA, advancing personalized diabetes treatment.
- The findings offer insights into beta-cell regeneration mechanisms and the role of T regulatory Type 1 cells in LADA remission.
- This research paves the way for targeted LADA therapies and precision medicine in diabetes management.
