title: Early feeding and risk of type 1 diabetes: experiences from the Trial to Reduce Insulin-dependent diabetes mellitus in the Genetically at Risk (TRIGR).
abstract: Short-term breastfeeding and early exposure to complex dietary proteins, such as cow milk proteins and cereals, or to fruit, berries, and roots have been implicated as risk factors for β cell autoimmunity, clinical type 1 diabetes, or both. The Trial to Reduce Insulin-dependent diabetes mellitus in the Genetically at Risk (TRIGR) is an international, randomized, double-blind, controlled intervention trial designed to answer the question of whether weaning to an extensively hydrolyzed formula in infancy will decrease the risk of type 1 diabetes later in childhood. In our pilot study, weaning to a highly hydrolyzed formula decreased by ≈ 50% the cumulative incidence of one or more diabetes-associated autoantibodies by a mean age of 4.7 y. This finding was confirmed in a recent follow-up analysis to 10 y of age. Currently, the full-scale TRIGR takes place in 77 centers in 15 countries. The TRIGR initially recruited 5606 newborn infants with a family member affected by type 1 diabetes and enrolled 2159 eligible subjects who carried a risk-conferring HLA genotype. All recruited mothers were encouraged to breastfeed. The intervention lasted for 6-8 mo with a minimum study formula exposure time of 2 mo, and hydrolyzed casein and standard cow milk-based weaning formulas were compared. Eighty percent of the participants were exposed to the study formula. The overall retention rate over the first 5 y was 87%, and protocol compliance was 94%. The randomization code will be opened when the last recruited child turns 10 y of age (ie, in 2017).
authors.affiliation: Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. mikael.knip@helsinki.fi
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.forename: Suvi M
authors.initials: SM
authors.lastname: Virtanen
authors.forename: Dorothy
authors.initials: D
authors.lastname: Becker
authors.forename: John
authors.initials: J
authors.lastname: Dupré
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Krischer
authors.forename: Hans K
authors.initials: HK
authors.lastname: Åkerblom
mesh_terms: D015551:Autoimmunity / Q000276:immunology; D001942:Breast Feeding; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D004044:Dietary Proteins / Q000008:administration & dosage; D004311:Double-Blind Method; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D015994:Incidence; D007223:Infant; D041943:Infant Formula / Q000008:administration & dosage*; D007231:Infant, Newborn; D008894:Milk Proteins / Q000008:administration & dosage*; D015337:Multicenter Studies as Topic; D010865:Pilot Projects; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D014886:Weaning
chemical_list: D004044:Dietary Proteins; D006680:HLA Antigens; D008894:Milk Proteins