Long-Term Study Shows GAD-alum May Delay Type 1 Diabetes in Some Children

The DiAPREV-IT trial tested whether GAD-alum—a form of the protein GAD65 combined with alum—could help prevent or delay type 1 diabetes in children at high risk. Researchers recruited children ages 4 to 18 who had antibodies against GAD (GADA) and at least one additional islet autoantibody, meaning their immune systems were already attacking the insulin-producing cells in their pancreas. About 50 children received two injections of GAD-alum spaced 30 days apart, while another 50 received placebo injections. All participants were followed for five years.

When the original trial ended in 2017, researchers did not find a statistically significant difference between the treatment and placebo groups in preventing stage 3 type 1 diabetes—the stage when blood sugar control becomes noticeably abnormal. However, a new analysis has now examined what happened to these children over a longer time period by checking the Swedish National Diabetes Registry and contacting participants directly.

The extended follow-up revealed that GAD-alum did delay the time to stage 3 type 1 diabetes diagnosis in children who carried a specific genetic variation: the HLA-DR3-DQ2 haplotype. This genetic marker influences how a person's immune system recognizes and responds to foreign substances. Children with this genetic profile who received GAD-alum developed stage 3 type 1 diabetes later than those who received placebo.

This finding suggests that genetic factors may play an important role in determining whether immune tolerance treatments work. Not all children with autoimmune diabetes may benefit equally from the same intervention, and identifying genetic markers could help researchers predict who might respond best to these approaches.

Immune tolerance trials like DiAPREV-IT are exploring whether carefully designed treatments can teach the immune system to stop attacking insulin-producing cells. GAD-alum represents one approach—introducing a small amount of a protein the immune system is already attacking, combined with alum (a substance that can modulate immune responses), in hopes of retraining the immune system.

The DiAPREV-IT follow-up demonstrates that even when a trial's main analysis doesn't show a treatment effect, longer-term data and analysis in specific subgroups can reveal important patterns. It also highlights why understanding individual differences—especially genetic ones—matters in developing more effective prevention strategies.

While delaying the onset of type 1 diabetes is not the same as preventing or curing it, a delay could mean additional years before people need insulin therapy and could allow more time for other treatments to be developed.

This was a small study involving children in Sweden who already showed signs of autoimmune attack on their pancreas. The findings apply specifically to children with the HLA-DR3-DQ2 genetic marker and do not necessarily predict outcomes for all children at risk for type 1 diabetes. More research is needed to confirm these results and understand how to identify which children might benefit from this or similar approaches.

Anyone interested in learning whether they or their child might be eligible for current immune tolerance trials should speak with their healthcare team or visit ClinicalTrials.gov to find studies recruiting in their area.

Source: Diabetologia. Evidence type: PubMed indexed literature. Type1Cure is an information and intelligence hub, not a medical advice service. This article summarizes published research and does not provide diagnosis, treatment, or personal medical guidance. Always talk to your own care team before changing anything about your Type 1 diabetes management.