Impact of Intranasal Insulin on Insulin Antibody Affinity and Isotypes in Young Children With HLA-Conferred Susceptibility to Type 1 Diabetes
- Samppa J. Ryhänen, MD, PHD1,
- Taina Härkönen, PHD1,
- Heli Siljander, MD, PHD1,2,
- Kirsti Näntö-salonen, MD, PHD3,
- Tuula Simell, PHD3,
- Heikki Hyöty, MD, PHD4,5,
- Jorma Ilonen, MD, PHD6,7,
- Riitta Veijola, MD, PHD8,
- Olli Simell, MD, PHD3 and
- Mikael Knip, MD, PHD1,2⇓
- 1Scientific Laboratory, Hospital for Children and Adolescents and Folkhälsan Research Center, University of Helsinki, Helsinki, Finland
- 2Department of Pediatrics, Tampere University Hospital, Tampere, Finland
- 3Department of Pediatrics, University of Turku, Turku, Finland
- 4Department of Virology, University of Tampere, Medical School, Tampere, Finland
- 5Center for Laboratory Medicine, Tampere University Hospital, Tampere, Finland
- 6Immunogenetics Laboratory, University of Turku, Turku, Finland
- 7Department of Clinical Microbiology, University of Kuopio, Kuopio, Finland
- 8Department of Pediatrics, University of Oulu, Oulu, Finland
- ↵Corresponding author: Mikael Knip, .
OBJECTIVE Despite promising results from studies on mouse models, intranasal insulin failed to prevent or delay the development of type 1 diabetes in autoantibody-positive children with HLA-conferred disease susceptibility. To analyze whether the insulin dose was inadequate to elicit an immunomodulatory response, we compared the changes observed in insulin antibody (IA) affinity and isotypes after treatment with nasal insulin or placebo.
RESEARCH DESIGN AND METHODS Ninety-five children (47 in the placebo group and 48 in the insulin group of the total of 224 children randomized for the trial) with HLA-conferred susceptibility to type 1 diabetes derived from the intervention arm of the Finnish Type 1 Diabetes Prediction and Prevention study were included in these analyses. Blood samples drawn before or at the beginning of the treatment and after treatment for 3 and 6 months were analyzed for IA affinity and isotype-specific IAs (IgG1–4, IgA, IgM, and IgE).
RESULTS IgG3- and IgA-IA levels (P = 0.031 and 0.015, respectively) and the number of IgG3-IA–positive subjects (P = 0.022) were significantly higher at 6 months after the initiation of the treatment in the insulin group. No significant differences were observed between the two groups in IA affinity or other IA isotypes.
CONCLUSIONS The insulin dose administered induced a modest change in the IA isotype profile. The lack of impact of nasal insulin on IA affinity implies that the immune response of study subjects was already mature at the beginning of the intervention.
- Received July 27, 2010.
- Accepted March 18, 2011.
- © 2011 by the American Diabetes Association.
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