High-dose oral insulin induces an immune response in children at high risk of developing type 1 diabetes but without causing hypoglycemia or triggering immune responses typical of type 1 diabetes, a pilot study showed.

Children aged 2-7 with a family history of type 1 diabetes and susceptible human leukocyte antigen class II genotypes – but without signs of islet autoimmunity – were randomized to either an escalating daily dose of oral insulin (n = 15) from 2.5 mg up to 67.5 mg for 3-18 months, or to placebo, according to a paper published April 21 in JAMA.

Five of the six children treated with 67.5 mg insulin showed increases in IgG binding, saliva IgA binding, and CD4+ T-cell proliferative responses to insulin, but there were no incidents of hypoglycemia, IgE responses to insulin, autoantibodies to glutamic acid decarboxylase, or insulinoma-associated antigen 2 (JAMA 2015; 313:1541-9 [ doi:10.1001/jama.2015.2928 ]).

“The immune response observed in insulin-treated children did not display the features typically associated with type 1 diabetes, such as a dominant proinflammatory IFNG CD4+ T-cell response,” wrote Dr. Ezio Bonifacio of the DFG Center for Regenerative Therapies, Dresden, Germany, and coauthors.

The study was supported by the Juvenile Diabetes Research Foundation, the Bundesministerium für Bildung und Forschung in Germany, the Deutsche Forschungs Gemeinschaft, and the German Center for Diabetes Research. Insulin crystals were provided by Lilly Pharmaceuticals. There were no other conflicts of interest declared.