Knip, Mikael3; Åkerblom, Hans K3; Becker, Dorothy16; Dosch, Hans-Michael5; Dupre, John6; Fraser, William7; Howard, Neville8; Ilonen, Jorma17; Krischer, Jeffrey P18; Kordonouri, Olga11; Lawson, Margaret L12; Palmer, Jerry P13; Savilahti, Erkki3; Vaarala, Outi14; Virtanen, Suvi M14; Mandrup-Poulsen, Thomas19
1 Section of Endocrinology Research, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet2 Department of Biomedical Sciences, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet3 University of Helsinki4 University of Pittsburgh5 University of Toronto6 University of Western Ontario, London, Canada.7 University of Montreal8 Children's Hospital of Westmead, Sydney, Australia.9 University of Turku10 University of South Florida11 Kinder- und Jugendkrankenhaus AUF DER BULT, Hannover, Germany.12 Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.13 University of Washington, Seattle.14 National Institute for Health and Welfare, Helsinki15 unknown16 University of Pittsburgh17 University of Turku18 University of South Florida19 Section of Endocrinology Research, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet
a randomized clinical trial
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.
Jama : the Journal of the American Medical Association, 2014, Vol 311, Issue 22, p. 2279-87