The POInT study has investigated whether treatment with oral insulin can prevent diabetes-related autoantibodies and type 1 diabetes in children with an increased genetic risk of developing the disease. These autoantibodies are used as biomarkers for type 1 diabetes and the presence of two or more autoantibodies is called early-stage type 1 diabetes. The international study includes 1,050 children from Sweden, Germany, Poland, Belgium and the United Kingdom. Half of the participants received daily treatment with oral insulin, and the other half received placebo during their first three years of life. In type 1 diabetes, the body鈥檚 immune system attacks the insulin-producing beta cells in the pancreas and destroys them.
鈥淭he children who have participated in the study have made a huge effort together with their parents. Oral insulin is absorbed by the oral cavity and digestive tract and we have investigated whether treatment of children with an increased risk of the disease can train the immune system to tolerate the body鈥檚 own insulin,鈥 says Helena Elding Larsson, principal investigator for the Swedish part of POInT and coauthor of the article in The Lancet.
Delayed the rate of disease progression
There was no evidence that high-dose of daily oral insulin can prevent the development of diabetes-related autoantibodies. However, oral insulin delayed the progression rate of disease in children who developed diabetes-related autoantibodies. The researchers compared the rate of progression from occurrence of two or more diabetes-related autoantibodies to clinical diabetes and found that the rate was reduced by almost 50 per cent in oral insulin-treated participants.
鈥淲e had hoped to see that oral insulin could prevent the development of diabetes-related autoantibodies. However, it is encouraging that oral insulin seems to delay the progression rate of the disease in children with diabetes-related autoantibodies, and we need to confirm these results in new studies. Type 1 diabetes is a difficult disease to live with, and it can mean a lot if it is possible to delay disease progression by a few years. This means fewer years of insulin treatment and a reduced risk of complications,鈥 says Helena Elding Larsson, professor of autoimmune diseases at Lund University Diabetes Centre and paediatrician at Sk氓ne University Hospital.
Genetic mapping of children鈥檚 risk of developing type 1 diabetes has helped the researchers to identify a group that could particularly benefit from the treatment. Oral insulin was associated with substantial protection against the development of diabetes in participants with a specific genotype, which was present in over half of the participants, and is found in about 60 per cent of people with type 1 diabetes.
鈥淚t is far too early to draw firm conclusions as it is a small group of children. It would be very interesting to see follow-up studies by the research sites on a careful selection of children. The study shows that high-dose oral insulin immunotherapy is a safe treatment that does not cause serious side effects,鈥 says Markus Lundgren, researcher in paediatric endocrinology at Lund University Diabetes Centre and co-principal investigator for the Swedish part of the study.
Protect insulin-producing cells
Teplizumab is currently the only approved drug in some countries that can be given to children who have developed diabetes-related autoantibodies. At Lund University Diabetes Centre, several studies are investigating whether it is possible to prevent or delay the onset of type 1 diabetes in children with an increased risk of developing the disease at an even earlier stage.
鈥淲e are at an interesting point in [BR1] diabetes research and an important goal for us is to identify safe treatments that can be given to children at an early stage. The results from POInT suggest that preventive treatments may have to be tailored to genetic risk variants. We have good insulin pumps and diabetes products for people affected by type 1 diabetes, but we need to develop new treatments that can protect the insulin-producing cells at different stages of life,鈥 says Helena Elding Larsson.
Anette-Gabriele Ziegler is the lead researcher of the international POInT study. She agrees that the study is pointing towards new possibilities for genetically tailored prevention strategies.
鈥淭he POInT study will change how we approach antigen-based therapies in type 1 diabetes. While the oral insulin therapy could not prevent the development of islet autoantibodies as we had hoped, the trial data suggest that this therapy may positively influence the course of the disease,鈥 says Anette-Gabriele Ziegler, chair of Diabetes and Gestational Diabetes at the TUM University Hospital and professor and director of the Helmholtz Munich Institute of Diabetes Research in Germany.
