Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes Academic Article uri icon

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abstract

  • Importance: Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. Objective: To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. Design, Setting, and Participants: An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-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; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. Interventions: The participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. Main Outcomes and Measures: Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). Results: Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). Conclusions and Relevance: Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes. Trial Registration: clinicaltrials.gov Identifier: NCT00179777.

authors

  • Andrighetti, Santina
  • Knip, Mikael
  • Åkerblom, Hans K
  • Al Taji, Eva
  • Becker, Dorothy
  • Bruining, Jan
  • Castano, Luis
  • Danne, Thomas
  • de Beaufort, Carine
  • Dosch, Hans-Michael
  • Dupre, John
  • Fraser, William D
  • Howard, Neville
  • Ilonen, Jorma
  • Konrad, Daniel
  • Kordonouri, Olga
  • Krischer, Jeffrey P
  • Lawson, Margaret L
  • Ludvigsson, Johnny
  • Madacsy, Laszlo
  • Mahon, Jeffrey L
  • Ormisson, Anne
  • Palmer, Jerry P
  • Pozzilli, Paolo
  • Savilahti, Erkki
  • Serrano-Rios, Manuel
  • Songini, Marco
  • Taback, Shayne
  • Vaarala, Outi
  • White, Neil H
  • Virtanen, Suvi M
  • Wasikowa, Renata

publication date

  • January 2, 2018