Tags

Type your tag names separated by a space and hit enter

Hydrolyzed infant formula and early β-cell autoimmunity: a randomized clinical trial.

Abstract

IMPORTANCE

The disease process leading to clinical type 1 diabetes often starts during the first years of life. Early exposure to complex dietary proteins may increase the risk of β-cell autoimmunity in children at genetic risk for type 1 diabetes. Extensively hydrolyzed formulas do not contain intact proteins.

OBJECTIVE

To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of diabetes-associated autoantibodies in young children.

DESIGN, SETTING, AND PARTICIPANTS

A double-blind randomized clinical trial of 2159 infants with HLA-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1078 were randomized to be weaned to the extensively hydrolyzed casein formula and 1081 were randomized to be weaned to a conventional cows' milk-based formula. The participants were observed to April 16, 2013.

INTERVENTIONS

The participants received either a casein hydrolysate or a conventional cows' milk formula supplemented with 20% of the casein hydrolysate.

MAIN OUTCOMES

AND MEASURES: Primary outcome was positivity for at least 2 diabetes-associated autoantibodies out of 4 analyzed. Autoantibodies to insulin, glutamic acid decarboxylase, and the insulinoma-associated-2 (IA-2) molecule were analyzed using radiobinding assays and islet cell antibodies with immunofluorescence during a median observation period of 7.0 years (mean, 6.3 years).

RESULTS

The absolute risk of positivity for 2 or more islet autoantibodies was 13.4% among those randomized to the casein hydrolysate formula (n = 139) vs 11.4% among those randomized to the conventional formula (n = 117). The unadjusted hazard ratio for positivity for 2 or more autoantibodies among those randomized to be weaned to the casein hydrolysate was 1.21 (95% CI, 0.94-1.54), compared with those randomized to the conventional formula, while the hazard ratio adjusted for HLA risk, duration of breastfeeding, vitamin D use, study formula duration and consumption, and region was 1.23 (95% CI, 0.96-1.58). There were no clinically significant differences in the rate of reported adverse events between the 2 groups.

CONCLUSIONS AND RELEVANCE

Among infants at risk for type 1 diabetes, the use of a hydrolyzed formula, when compared with a conventional formula, did not reduce the incidence of diabetes-associated autoantibodies after 7 years. These findings do not support a benefit from hydrolyzed formula. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00179777.

Links

  • PMC Free PDF
  • PMC Free Full Text
  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    University of Helsinki, Helsinki, Finland.

    ,

    University of Helsinki, Helsinki, Finland.

    ,

    University of Pittsburgh, Pittsburgh, Pennsylvania.

    ,

    University of Toronto, Toronto, Ontario, Canada.

    ,

    University of Western Ontario, London, Canada.

    ,

    University of Montréal, Montréal, Québec, Canada.

    ,

    Children's Hospital of Westmead, Sydney, Australia.

    ,

    University of Turku, Turku, Finland.

    ,

    University of South Florida, Tampa.

    ,

    Kinder- und Jugendkrankenhaus AUF DER BULT, Hannover, Germany.

    ,

    Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.

    ,

    University of Washington, Seattle.

    ,

    University of Helsinki, Helsinki, Finland.

    ,

    National Institute for Health and Welfare, Helsinki, Finland.

    ,

    National Institute for Health and Welfare, Helsinki, Finland.

    Source

    JAMA 311:22 2014 Jun 11 pg 2279-87

    MeSH

    Animals
    Autoantibodies
    Autoimmunity
    Breast Feeding
    Caseins
    Child
    Diabetes Mellitus, Type 1
    Dietary Proteins
    Double-Blind Method
    Female
    Follow-Up Studies
    Humans
    Hydrolysis
    Incidence
    Infant Formula
    Infant, Newborn
    Insulin-Secreting Cells
    Male
    Milk
    Risk
    Weaning

    Pub Type(s)

    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    24915259

    Citation

    Knip, Mikael, et al. "Hydrolyzed Infant Formula and Early Β-cell Autoimmunity: a Randomized Clinical Trial." JAMA, vol. 311, no. 22, 2014, pp. 2279-87.
    Knip M, Åkerblom HK, Becker D, et al. Hydrolyzed infant formula and early β-cell autoimmunity: a randomized clinical trial. JAMA. 2014;311(22):2279-87.
    Knip, M., Åkerblom, H. K., Becker, D., Dosch, H. M., Dupre, J., Fraser, W., ... Virtanen, S. M. (2014). Hydrolyzed infant formula and early β-cell autoimmunity: a randomized clinical trial. JAMA, 311(22), pp. 2279-87. doi:10.1001/jama.2014.5610.
    Knip M, et al. Hydrolyzed Infant Formula and Early Β-cell Autoimmunity: a Randomized Clinical Trial. JAMA. 2014 Jun 11;311(22):2279-87. PubMed PMID: 24915259.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Hydrolyzed infant formula and early β-cell autoimmunity: a randomized clinical trial. AU - Knip,Mikael, AU - Åkerblom,Hans K, AU - Becker,Dorothy, AU - Dosch,Hans-Michael, AU - Dupre,John, AU - Fraser,William, AU - Howard,Neville, AU - Ilonen,Jorma, AU - Krischer,Jeffrey P, AU - Kordonouri,Olga, AU - Lawson,Margaret L, AU - Palmer,Jerry P, AU - Savilahti,Erkki, AU - Vaarala,Outi, AU - Virtanen,Suvi M, AU - ,, PY - 2014/6/11/entrez PY - 2014/6/11/pubmed PY - 2014/6/24/medline SP - 2279 EP - 87 JF - JAMA JO - JAMA VL - 311 IS - 22 N2 - IMPORTANCE: The disease process leading to clinical type 1 diabetes often starts during the first years of life. Early exposure to complex dietary proteins may increase the risk of β-cell autoimmunity in children at genetic risk for type 1 diabetes. Extensively hydrolyzed formulas do not contain intact proteins. OBJECTIVE: To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of diabetes-associated autoantibodies in young children. DESIGN, SETTING, AND PARTICIPANTS: A double-blind randomized clinical trial of 2159 infants with HLA-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1078 were randomized to be weaned to the extensively hydrolyzed casein formula and 1081 were randomized to be weaned to a conventional cows' milk-based formula. The participants were observed to April 16, 2013. INTERVENTIONS: The participants received either a casein hydrolysate or a conventional cows' milk formula supplemented with 20% of the casein hydrolysate. MAIN OUTCOMES: AND MEASURES: Primary outcome was positivity for at least 2 diabetes-associated autoantibodies out of 4 analyzed. Autoantibodies to insulin, glutamic acid decarboxylase, and the insulinoma-associated-2 (IA-2) molecule were analyzed using radiobinding assays and islet cell antibodies with immunofluorescence during a median observation period of 7.0 years (mean, 6.3 years). RESULTS: The absolute risk of positivity for 2 or more islet autoantibodies was 13.4% among those randomized to the casein hydrolysate formula (n = 139) vs 11.4% among those randomized to the conventional formula (n = 117). The unadjusted hazard ratio for positivity for 2 or more autoantibodies among those randomized to be weaned to the casein hydrolysate was 1.21 (95% CI, 0.94-1.54), compared with those randomized to the conventional formula, while the hazard ratio adjusted for HLA risk, duration of breastfeeding, vitamin D use, study formula duration and consumption, and region was 1.23 (95% CI, 0.96-1.58). There were no clinically significant differences in the rate of reported adverse events between the 2 groups. CONCLUSIONS AND RELEVANCE: Among infants at risk for type 1 diabetes, the use of a hydrolyzed formula, when compared with a conventional formula, did not reduce the incidence of diabetes-associated autoantibodies after 7 years. These findings do not support a benefit from hydrolyzed formula. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00179777. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/24915259/Hydrolyzed_infant_formula_and_early_β_cell_autoimmunity:_a_randomized_clinical_trial_ L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2014.5610 DB - PRIME DP - Unbound Medicine ER -