Dietary intervention in infancy and later signs of beta-cell autoimmunity
Mikael Knip, Suvi M Virtanen, Karri Seppä, Jorma Ilonen, Erkki Savilahti, Outi Vaarala, Antti Reunanen, Kari Teramo, Anu-Maaria Hämäläinen, Johanna Paronen, Hans-Michael Dosch, Timo Hakulinen, Hans K Akerblom, Finnish TRIGR Study Group, H K Åkerblom, V Eskola, H Haavisto, A-M Hämäläinen, C Holm, A-L Järvenpää, R Jokisalo, M-L Käär, U Kaski, J Komulainen, P Korpela, P Lautala, K Niemi, A Nuuja, P Rantanen, R Renko, M Renlund, M Salo, T Talvitie, T Uotila, G Wetterstrand, H Hyöty, J Ilonen, P Klemetti, M Knip, P K Kulmala, J Paronen, A Reunanen, T Saukkonen, E Savilahti, K Savola, K Teramo, O Vaarala, S M Virtanen, Mikael Knip, Suvi M Virtanen, Karri Seppä, Jorma Ilonen, Erkki Savilahti, Outi Vaarala, Antti Reunanen, Kari Teramo, Anu-Maaria Hämäläinen, Johanna Paronen, Hans-Michael Dosch, Timo Hakulinen, Hans K Akerblom, Finnish TRIGR Study Group, H K Åkerblom, V Eskola, H Haavisto, A-M Hämäläinen, C Holm, A-L Järvenpää, R Jokisalo, M-L Käär, U Kaski, J Komulainen, P Korpela, P Lautala, K Niemi, A Nuuja, P Rantanen, R Renko, M Renlund, M Salo, T Talvitie, T Uotila, G Wetterstrand, H Hyöty, J Ilonen, P Klemetti, M Knip, P K Kulmala, J Paronen, A Reunanen, T Saukkonen, E Savilahti, K Savola, K Teramo, O Vaarala, S M Virtanen
Abstract
Background: Early exposure to complex dietary proteins may increase the risk of beta-cell autoimmunity and type 1 diabetes in children with genetic susceptibility. We tested the hypothesis that supplementing breast milk with highly hydrolyzed milk formula would decrease the cumulative incidence of diabetes-associated autoantibodies in such children.
Methods: In this double-blind, randomized trial, we assigned 230 infants with HLA-conferred susceptibility to type 1 diabetes and at least one family member with type 1 diabetes to receive either a casein hydrolysate formula or a conventional, cow's-milk-based formula (control) whenever breast milk was not available during the first 6 to 8 months of life. Autoantibodies to insulin, glutamic acid decarboxylase (GAD), the insulinoma-associated 2 molecule (IA-2), and zinc transporter 8 were analyzed with the use of radiobinding assays, and islet-cell antibodies were analyzed with the use of immunofluorescence, during a median observation period of 10 years (mean, 7.5). The children were monitored for incident type 1 diabetes until they were 10 years of age.
Results: The unadjusted hazard ratio for positivity for one or more autoantibodies in the casein hydrolysate group, as compared with the control group, was 0.54 (95% confidence interval [CI], 0.29 to 0.95), and the hazard ratio adjusted for an observed difference in the duration of exposure to the study formula was 0.51 (95% CI, 0.28 to 0.91). The unadjusted hazard ratio for positivity for two or more autoantibodies was 0.52 (95% CI, 0.21 to 1.17), and the adjusted hazard ratio was 0.47 (95% CI, 0.19 to 1.07). The rate of reported adverse events was similar in the two groups.
Conclusions: Dietary intervention during infancy appears to have a long-lasting effect on markers of beta-cell autoimmunity--markers that may reflect an autoimmune process leading to type 1 diabetes. (ClinicalTrials.gov number, NCT00570102.).
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Source: PubMed