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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.
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Dr. Jay Skylar |
One hope for preventing the onset of type 1 diabetes in high-risk individuals has been that therapy with a diabetes-related antigen, administered in a manner that favors immune regulation rather than immune aggression (activation of effector T lymphocytes directed against beta cells), could achieve protection without compromising general immune response – basically antigen-based vaccination.
So far, attempts at both primary prevention – before seroconversion – and secondary prevention in individuals with diabetes-related autoantibodies, have not been successful.
However, this 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.
Dr. Jay A. Skyleris at the University of Miami. These comments are taken from an accompanying editorial (JAMA 2015, April 21 [doi:10.1001/jama.2015.2054]. Dr Skyler disclosed personal fees, stock options, and grants from a range of pharmaceutical companies.
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|
Dr. Jay Skylar |
One hope for preventing the onset of type 1 diabetes in high-risk individuals has been that therapy with a diabetes-related antigen, administered in a manner that favors immune regulation rather than immune aggression (activation of effector T lymphocytes directed against beta cells), could achieve protection without compromising general immune response – basically antigen-based vaccination.
So far, attempts at both primary prevention – before seroconversion – and secondary prevention in individuals with diabetes-related autoantibodies, have not been successful.
However, this 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.
Dr. Jay A. Skyleris at the University of Miami. These comments are taken from an accompanying editorial (JAMA 2015, April 21 [doi:10.1001/jama.2015.2054]. Dr Skyler disclosed personal fees, stock options, and grants from a range of pharmaceutical companies.
|
|
Dr. Jay Skylar |
One hope for preventing the onset of type 1 diabetes in high-risk individuals has been that therapy with a diabetes-related antigen, administered in a manner that favors immune regulation rather than immune aggression (activation of effector T lymphocytes directed against beta cells), could achieve protection without compromising general immune response – basically antigen-based vaccination.
So far, attempts at both primary prevention – before seroconversion – and secondary prevention in individuals with diabetes-related autoantibodies, have not been successful.
However, this 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.
Dr. Jay A. Skyleris at the University of Miami. These comments are taken from an accompanying editorial (JAMA 2015, April 21 [doi:10.1001/jama.2015.2054]. Dr Skyler disclosed personal fees, stock options, and grants from a range of pharmaceutical companies.
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.
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.
Key clinical point: High-dose oral insulin induced an immune response in children at high risk of developing type 1 diabetes without causing hypoglycemia.
Major finding: 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.
Data source: A prospective, randomized pilot study in 25 children with a family history of type 1 diabetes.
Disclosures: 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.
