Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes: a pilot study

H K Akerblom, S M Virtanen, J Ilonen, E Savilahti, O Vaarala, A Reunanen, K Teramo, A-M Hämäläinen, J Paronen, M-A Riikjärv, A Ormisson, J Ludvigsson, H-M Dosch, T Hakulinen, M Knip, National TRIGR Study Groups, H K Akerblom, S M Virtanen, J Ilonen, E Savilahti, O Vaarala, A Reunanen, K Teramo, A-M Hämäläinen, J Paronen, M-A Riikjärv, A Ormisson, J Ludvigsson, H-M Dosch, T Hakulinen, M Knip, National TRIGR Study Groups

Abstract

Aims/hypothesis: We aimed to assess the feasibility of a dietary intervention trial with weaning to hydrolysed formula in infants at increased risk of type 1 diabetes and to study the effect of the intervention on the emergence of diabetes-associated autoantibodies in early childhood.

Methods: We studied 242 newborn infants who had a first-degree relative with type 1 diabetes and carried risk-associated HLA-DQB1 alleles. After exclusive breastfeeding, the infants underwent a double-blind, randomised pilot trial of either casein hydrolysate (Nutramigen; Mead Johnson) or conventional cow's milk-based formula until the age of 6-8 months. During a mean observation period of 4.7 years, autoantibodies to insulin, anti-glutamic acid decarboxylase and insulinoma-associated antigen-2 were measured by radiobinding assays, and islet cell antibodies (ICA) by immunofluorescence.

Results: The feasibility of screening and identifying a cohort of first-degree relatives with HLA-conferred disease susceptibility, enrolling them in a dietary intervention trial and following them for seroconversion to autoantibody positivity is established. The cumulative incidence of autoantibodies was somewhat smaller in the casein hydrolysate vs control formula group, suggesting the need for a larger well-powered study. After adjustment for duration of study formula feeding, life-table analysis showed a significant protection by the intervention from positivity for ICA (p=0.02) and at least one autoantibody (p=0.03).

Conclusions/interpretation: The present study provides the first evidence ever in man, despite its limited power, that it may be possible to manipulate spontaneous beta cell autoimmunity by dietary intervention in infancy.

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Source: PubMed

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