Daily high-dose oral insulin compared with placebo resulted in an immune response to insulin without hypoglycemia among children at high risk for type 1 diabetes, according to study findings published in JAMA.
“Antigen-specific therapy with insulin before the development of autoantibodies may induce protective immune responses that prevent the emergence of autoimmunity and type 1 diabetes in genetically at-risk children,” the researchers wrote. “Therefore, we assessed whether oral insulin in children without prior overt autoimmunity can induce a potentially protective immune response to an autoantigen without causing adverse effects.”
Ezio Bonifacio, PhD, of the DFG Center for Regenerative Therapies in Dresden, Germany, and colleagues evaluated 25 islet autoantibody-negative children aged 2 to 7 years from the Pre-POINT study to determine the immune responses and adverse events association with orally administered insulin. Participants had a family history of type 1 diabetes and were susceptible to human leukocyte antigen class II genotypes.
Participants were randomly assigned to oral insulin (n = 15) or placebo (n = 10) once daily for 3 to 18 months. Dose escalations from 2.5 mg to 7.5 mg (n = 3), 2.5 mg to 22.5 mg (n = 3) or 7.5 mg to 67.5 mg (n = 3) were administered to nine participants after 6 months and six participants received only 22.5 mg (n = 3) or 67.5 mg (n = 3).
Study researcher Anette-Gabriele Ziegler, MD, from the Institut für Diabetesforschung in Germany, said in a press release that the unique aspect of the study is that the insulin was administered as a prophylactic before the participants developed an autoimmune response.
“This is a revolutionary way to prevent type 1 diabetes, but it is quite logical that if the body’s immune system doesn’t learn how to make the protective responses by itself, we need to give it a little help,” Ziegler said.
Sixty percent of participants in the insulin group and 20% in the placebo group had antibody or T-cell responses (P = .02 for trend).
Immune responses to insulin also were revealed for one participant treated with 2.5 mg, one participant treated with 7.5 mg, two treated with 22.5 mg, five treated with 67.5 mg and one treated with placebo (P = .051).
“In this pilot study of children at high risk for type 1 diabetes, daily oral administration of 67.5 mg of insulin, compared with placebo, results in an immune response without hypoglycemia,” the researchers wrote. “These findings support the need for a phase 3 trial to determine whether oral insulin can prevent islet autoimmunity and diabetes in such children.”
In an accompanying editorial, Jay S. Skyler, MD, of the University of Miami Miller School of Medicine, wrote that the identification of children at increased risk for type 1 diabetes at birth is now possible.
“What is missing are interventions to arrest this process prior to irreversible damage to the pancreatic beta cell,” he wrote. “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.” – by Amber Cox
Disclosure: The researchers report no relevant financial disclosures.