To mark World Diabetes Day on November 14, Israeli researchers say they have found a treatment that can restore normal blood sugar levels in about 30% of mice with latent autoimmune diabetes in adults, or LADA.
LADA is similar to type 1 diabetes because the body’s immune system attacks its own insulin-producing cells. Yet it is also similar to type 2 diabetes, which occurs in adulthood without the immediate need for daily insulin. Therefore, LADA, colloquially known as “type 1.5 diabetes,” presents a diagnostic and therapeutic challenge.
Now, scientists from the Azrieli Faculty of Medicine at Bar-Ilan University have demonstrated a potential breakthrough using an experimental combination of three drugs tested in mice engineered to exhibit conditions mimicking LADA.
Dr. Ron Piran, who led the study, and Wisal Sawaed, the lead author, told The Times of Israel in a video call that a third of the treated animals achieved complete remission after receiving the drug cocktail of GABA, a neurotransmitter that supports beta cell function and relieves inflammation; sitagliptin, a standard diabetes medication that helps regulate insulin; and omeprazole, a widely prescribed acid reflux inhibitor.
Additionally, the research team led by Dr. Shira Perez, director of the faculty’s Genomics Center, identified specific RNA biomarkers in blood samples that accurately predicted which of the mice would respond to the protocol.
The study, published in MedComm, could lead to improved targeted treatment for humans.
“My 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,” Sawaed said.
Diabetes on the rise worldwide
In healthy individuals, the human body breaks down food into glucose and relies on the hormone insulin to move sugar from the bloodstream into cells for energy.
People with type 1 diabetes have an autoimmune disease in which the immune system destroys the pancreas’ ability to produce insulin. People with type 2 diabetes initially continue to produce insulin, but their blood sugar levels continue to rise. Unlike type 2 diabetes, LADA develops primarily because the immune system attacks insulin-producing cells, rather than because of insulin resistance or obesity.
Nearly 600 million adults (20 to 79 years) live with diabetes worldwide, and this number is expected to reach 853 million by 2050.
In Israel, approximately 548,000 people aged 18 and older had diabetes in 2021, or nearly 10% of the adult population, according to data from the National Program for Community Health Care Quality Indicators.
This figure is higher than the OECD average of 6.7% of the adult population. Data also shows that individuals in the lowest socioeconomic bracket face a higher risk of developing this disease, largely due to reduced access to nutritious foods, higher rates of obesity and chronic stress.
LADA is often misdiagnosed
“LADA accounts for 9.1% of all diabetes cases (worldwide),” Sawaed said.
“It’s a very common form of diabetes,” Piran added. “It’s a lot more common than you think.”
Piran said he began the research after someone asked him about a 60-year-old patient who had been diagnosed with high blood sugar, a hallmark of type 2 diabetes, but whose condition was getting worse.
A C-peptide test revealed that the patient had surprisingly low insulin production, which is not characteristic of early-onset type 2 diabetes.
“So we started thinking about LADA, which is not as well-known a diabetes as the other two,” Piran said.
Sawaed joined research for her master’s degree, then pursued her doctorate, becoming the first person from Salama, the Bedouin village in Galilee where she grew up, to receive a doctorate.
Giving the drug combination to mice
Although each of the three drugs was studied individually, the research team sought to see whether their combination could achieve two goals: reducing the autoimmune attack on the pancreas while encouraging the recovery of insulin-producing cells.
Sawaed said that during the study, when she treated adult mice with the three drugs, “a third of them were cured.”
Their blood sugar levels returned to normal, they no longer needed insulin, and they remained diabetes-free for weeks after treatment ended, she said.
The mice had developed new insulin-producing cells, mainly through the active replication of existing cells in the pancreas.
“The remaining mice, however, showed little or no response to the therapy,” Piran said.
In search of biomarkers
The researchers then looked to see if they could predict which mice would respond to the treatment and brought in Perez, who analyzed blood samples taken before the treatment.
Perez’s team identified two cell-free RNA (cfRNA) biomarkers, Adgrb1 and Chd5, that distinguished mice that would recover from those that would not.
“These RNA markers suggested to us that the animals with these specific markers were the ones responding to treatment,” Piran said. “This is an important step toward precision medicine for autoimmune diabetes. »
Instead of “exposing every patient to the same therapy,” he said, “we may one day be able to identify those who are most likely to benefit before treatment even begins.”
Piran added that the research paper’s second author, Ahmad Dallasheh, was studying whether human patients had similar RNA signatures.
“It’s an ongoing project,” Piran said, adding that the next step would be to conduct a human clinical trial with the three drugs.
“The reason we can go straight to a clinical trial is because these three drugs are already on the market and approved by the FDA,” he said. “We don’t need to prove their safety, and people are already taking them.”
For now, Sawaed said it’s important for individuals to know the type of diabetes they have.
“People go to the doctor, and if they’re over 30, they automatically assume they have type 2 diabetes,” she said. “But people should do the C-peptide test to get the right diagnosis and treatment. I think that’s the important thing.”
Gn Health
