Researchers at Bar-Ilan University’s Azrieli Faculty of Medicine have identified blood biomarkers that accurately predict which mice would respond to an experimental combination therapy for latent autoimmune diabetes in adults (LADA), a form of autoimmune diabetes that is frequently mistaken for type 2 diabetes. The findings, published in MedComm , also show that the treatment restored normal blood sugar levels in about one-third of treated mice and stimulated the regeneration of insulin-producing cells in the pancreas.
LADA is often described as a slow-progressing form of type 1 diabetes. Because patients continue producing insulin during the early stages of the disease, they are commonly diagnosed with type 2 diabetes before the underlying autoimmune process is recognized. As a result, many patients initially receive treatments that are not optimally suited to their condition.
"There is tremendous variation in how patients respond to treatment for autoimmune diseases," said Dr. Ron Piran, of Bar-Ilan University's Azrieli Faculty of Medicine, the corresponding author of the study. "My Ph.D. student and the study’s lead author, Wisal Sawaed, developed this work as the basis of her doctoral dissertation. Her goal was not only to develop a more effective therapy, but also to determine whether we could predict in advance who would benefit from it."
The researchers tested a combination of three well-known drugs: gamma-aminobutyric acid (GABA), sitagliptin, and omeprazole in a mouse model that closely resembles human LADA. Although each medication has been studied individually, the team investigated whether combining them could simultaneously reduce the autoimmune attack on the pancreas while encouraging insulin-producing beta cells to recover.
The results were striking. Approximately 30% of the treated mice achieved complete remission. Their blood glucose levels returned to normal, they no longer required insulin, and they remained diabetes-free for weeks after treatment had ended. The remaining mice, however, showed little or no response to the therapy.
The researchers then sought to discover whether they could predict beforehand which animals would respond. Dr. Shira Perez, head of the faculty’s genomic center and her team analyzed blood samples collected before treatment and identified two cell-free RNA (cfRNA) biomarkers: Adgrb1 and Chd5, that distinguished future responders from non-responders. If validated in humans, these biomarkers could eventually help physicians tailor treatment to individual patients rather than relying on a one-size-fits-all approach.
"This is an important step toward precision medicine for autoimmune diabetes," said Dr. Piran. "Instead of exposing every patient to the same therapy, we may one day be able to identify those most likely to benefit before treatment even begins."
The study also provided new insights into how recovery occurred. Examination of the pancreases of cured mice revealed evidence that new insulin-producing beta cells had formed, suggesting that the pancreas had regained part of its lost function. The researchers found that this regeneration occurred predominantly through the replication of existing beta cells rather than simply preserving the cells that remained. They also found that the immune system became less likely to attack the pancreas, allowing the newly formed insulin-producing cells to survive and function.
Together, the findings suggest that successful treatment may require both calming the autoimmune response and promoting the pancreas's ability to regenerate.
"While these findings are encouraging, substantial additional research will be needed before this approach can be tested clinically," says Piran. "Nevertheless, our results demonstrate that it may be possible not only to predict who will respond to therapy, but also to restore insulin production even after autoimmune diabetes has begun."
LADA accounts for an estimated 2–12% of adult diabetes cases and is often underdiagnosed because its symptoms initially resemble those of type 2 diabetes. The researchers believe that combining predictive biomarkers with personalized therapies could ultimately improve treatment and preserve pancreatic function in patients with this form of diabetes.
World Diabetes Day is observed annually on November 14 to raise awareness of diabetes and its impact worldwide.
MedComm
Markers Predicting Cure With Combinatorial Treatment in a Mouse Model of Latent Autoimmune Diabetes in Adults
12-Jul-2026