Early feeding and risk of type 1 diabetes: Experiences from the Trial to Reduce Insulin-dependent diabetes mellitus in the Genetically at Risk (TRIGR)

Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 06/2011; 94(6 Suppl):1814S-1820S. DOI: 10.3945/ajcn.110.000711
Source: PubMed


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).

Full-text preview

Available from:
  • Source
    • "Besides genetic predisposition, it is important the interplay of environmental factors, such as the diet, infections and the use of antibiotics; particularly, the early feeding regimes may modify the risk of T1D later in the life. The uses of bovine proteincontaining infant formulas instead of breastfeeding, and the anticipated introduction of cereals in the infants diet, are two strongly associated factors with the autoimmunity processes [2]. Bovine caseins, the main proteins found in infant formula, and β-lactoglobulin, one of the most allergenic bovine milk proteins, have been associated with an increased risk for T1D, regardless of the presence of islet autoantibodies. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: T1D is an autoimmune disorder that has been related to leaky gut, possible due to feeding regimes during the first year of life. IgG reactivity against dietary proteins indirectly assess gut permeability disruption. The aim of this study was to evaluate the association of early feeding regimes with total serum IgG response against related dietary antigens (gliadins, bovine caseins and β-lactoglobulin) in children with T1D at onset and after two years of evolution, and to determine the relative distribution of specific IgG subclasses against these proteins. Methods: A case-control study with 47 T1D children and 15 healthy controls was performed. Their histories of feeding egimes during the first year of life were recorded and a blood sample was collected at the time of the interview. Total IgG indexes and its subclasses (IgG1-4) were determined by ELISA using monoclonal antibodies. Results: An earlier introduction of cow’s milk in T1D children was observed as compared to healthy controls. No associations between early diet and the current presence of IgG antibodies were found. However, T1D patients had increased total IgG reactivity to gliadins, caseins and/or β-lactoglobulin. These increases were mainly associated with IgG1, IgG2 and IgG4 subclasses, as observed in other autoimmune diseases with intestinal origin as celiac disease. Gliadins showed the highest potential as antigens in T1D. Conclusions: The IgG reactivity patterns found in T1D children contributes to understand the effects of leaky gut in T1D and the aberrant immune response associated with intolerances and autoimmunity.
    Full-text · Article · Jan 2016
  • Source
    • "This leads to a state of unresponsiveness to dietary proteins such as BSA that can be developed in adults owing to prolonged minimal antigenic stimulation (Zeng et al., 2013). Bovine serum albumin and BI are among the most putative environmental diet-related risk factors implicated in the initiation of the immune-mediated pancreatic beta-cell destruction, which can be attributed among various factors to early exposure of genetically susceptible infants to bovine-based formulae as their first foreign dietary supplement (Knip et al., 2011; Ziegler et al., 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study was to examine the possible binding of bovine insulin (BI) with bovine serum albumin (BSA) to form a new potential diabetogenic irreversible complex protein. Several preparations of BSA and BI were prepared. Both capillary electrophoresis and spectrophotometric analysis were undertaken to test the possibility of complexation between BI and BSA. HPLC was used to test whether the potential complex of BI and BSA is reversible or irreversible. The optimum deviation between the real and calculated absorbances was observed at a BI/BSA ratio of 2. Moreover, the migration time of BI decreased substantially with increasing ratio of BI to BSA until it became almost constant at equal molar ratio of BI/BSA. While the majority of the 2:1 BI-BSA sample detached during the HPLC analysis, which confirms the reversible character of BI-BSA binding, the HPLC chromatogram also emphasizes the formation of an irreversible complexation between the two proteins. This study provides evidence of the formation of reversible and irreversible new BI-BSA complexes under physiological conditions. This highlights the importance of examining the possible diabetogenicity of BI-BSA complex in genetically susceptible people. Copyright © 2013 John Wiley & Sons, Ltd.
    Full-text · Article · Mar 2014 · Biomedical Chromatography
  • Source
    • "Low sun exposure Low level of vitamin D [4] Short breast feeding Lack of anti-inflammatory cytokines [44] [45] Early cow milk exposure Lack of anti-inflammatory cytokines [44] [45] Hygiene Lack of multifactorial exposure of antigens [7] Weight gain Beta cell stress [10] Viruses Infection/transformation of beta cells [46] M. Landin-Olsson et al. / Medical Hypotheses 81 (2013) 338–342 339 biochemical properties. The content of protein in wheat is around 12% to be compared with typical protein containing food such as meat and fish, where the protein content is around 20%. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The incidence of type 1 diabetes among children has almost doubled during the last decades in Sweden. Type 1 diabetes is considered as an autoimmune disease with unknown aetiology. Here we propose that the immune reaction may be initiated by food-derived mechanisms. The incidence of diabetes parallels an increased consumption of pasta, white bread, meat, cheese, low-fat milk, exotic fruits, soda, and snacks. Simultaneously, the consumption of potatoes, butter, high-fat milk, and domestic fruit has decreased. Three categories of food related reaction mechanisms are discussed against the following items (1) proteins from wheat, meat, and milk, (2) fat from processed food, and (3) exotic fruits. The current food consumption is suggested to initiate a pro-inflammatory reaction in the intestine and thereby reduce the intestinal barrier function. This may influence tolerance development and thus pave the way for an autoimmune attack on pancreatic beta cells.
    Full-text · Article · May 2013 · Medical Hypotheses
Show more