In a pilot study that included children at high risk for type 1 diabetes, daily high-dose oral insulin, compared with placebo, resulted in an immune response to insulin without hypoglycemia. According to the researchers, the findings that support the need for a phase 3 trial to determine whether oral insulin can prevent islet autoimmunity and diabetes in high-risk children, according to a study in the April 21 issue of JAMA.

A few specific proteins are often the trigger for immune responses that cause autoimmune diseases. This has led to the experimental use of antigen­specific therapies (using a substance to initiate an immune response) to prevent, stabilize, or reverse immune­related diseases, such as allergies and multiple sclerosis.

Type 1 diabetes is an autoimmune disease that can be detected in asymptomatic individuals by the presence of islet autoantibodies that develop in children. Antigen-specific therapy using insulin before the development of autoantibodies may induce protective immune responses that prevent the emergence of autoimmunity and subsequent type 1 diabetes in genetically at-risk children, according to background information in the article.

Ezio Bonifacio, PhD, of the DFG Center for Regenerative Therapies Dresden, Technische Universitat Dresden, Germany and colleagues randomly assigned autoantibody-negative, genetically at-risk children to receive oral insulin at varying doses (n = 15) or placebo (n = 10) once daily for 3 to 18 months to assess whether oral insulin can induce a potentially protective immune response without causing adverse effects. The study (Pre-POINT) was performed between 2009 and 2013 in Germany, Austria, the United States, and the United Kingdom and enrolled children age 2 to 7 years with a family history of type 1 diabetes.

Immune responses to insulin were observed in 2 of 10 (20%) placebo-treated children, in 1 of 6 (16.7 percent) children treated with 2.5 mg of insulin, 1 of 6 (16.7%) treated with 7.5 mg, 2 of 6 (33.3%) treated with 22.5 mg, and 5 of 6 (83.3%) treated with 67.5 mg of insulin.

The incidence and type of adverse events were not different between children who received placebo and children who received oral insulin, regardless of the insulin dose. Hypoglycemia was not observed at any of the tested doses.

“The Pre-POINT pilot study demonstrated that daily oral administration of 67.5 mg of insulin to genetically at-risk healthy children without signs of islet autoimmunity resulted in an immune response without hypoglycemia. The immune response observed in insulin-treated children did not display the features typically associated with type 1diabetes,” the authors wrote.

 “It is now possible to identify children at increased risk for type 1 diabetes at birth, and there is an identifiable sequence of events that culminates in impaired insulin secretion and overt type 1 diabetes,” writes Jay S. Skyler, M.D., of the University of Miami Miller School of Medicine, in an accompanying editorial.

“What is missing are interventions to arrest this process prior to irreversible damage to the pancreatic beta cell. The promise of autoantigen-specific therapy for prevention of type 1 diabetes in humans has yet to be realized. The Pre-POINT study provides additional evidence to inform trial design and increases enthusiasm for cautiously moving forward with a study of primary prevention in genetically screened children.”