Dietary intervention in infancy and later signs of beta-cell autoimmunity

N Engl J Med. 2010 Nov 11;363(20):1900-8. doi: 10.1056/NEJMoa1004809.


Background: Early exposure to complex dietary proteins may increase the risk of beta-cell autoimmunity and type 1 diabetes in children with genetic susceptibility. We tested the hypothesis that supplementing breast milk with highly hydrolyzed milk formula would decrease the cumulative incidence of diabetes-associated autoantibodies in such children.

Methods: In this double-blind, randomized trial, we assigned 230 infants with HLA-conferred susceptibility to type 1 diabetes and at least one family member with type 1 diabetes to receive either a casein hydrolysate formula or a conventional, cow's-milk-based formula (control) whenever breast milk was not available during the first 6 to 8 months of life. Autoantibodies to insulin, glutamic acid decarboxylase (GAD), the insulinoma-associated 2 molecule (IA-2), and zinc transporter 8 were analyzed with the use of radiobinding assays, and islet-cell antibodies were analyzed with the use of immunofluorescence, during a median observation period of 10 years (mean, 7.5). The children were monitored for incident type 1 diabetes until they were 10 years of age.

Results: The unadjusted hazard ratio for positivity for one or more autoantibodies in the casein hydrolysate group, as compared with the control group, was 0.54 (95% confidence interval [CI], 0.29 to 0.95), and the hazard ratio adjusted for an observed difference in the duration of exposure to the study formula was 0.51 (95% CI, 0.28 to 0.91). The unadjusted hazard ratio for positivity for two or more autoantibodies was 0.52 (95% CI, 0.21 to 1.17), and the adjusted hazard ratio was 0.47 (95% CI, 0.19 to 1.07). The rate of reported adverse events was similar in the two groups.

Conclusions: Dietary intervention during infancy appears to have a long-lasting effect on markers of beta-cell autoimmunity--markers that may reflect an autoimmune process leading to type 1 diabetes. ( number, NCT00570102.).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / blood*
  • Autoimmunity*
  • Biomarkers / blood
  • Caseins / adverse effects
  • Caseins / immunology
  • Caseins / therapeutic use
  • Child
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Disease Progression
  • Double-Blind Method
  • Genetic Predisposition to Disease*
  • Histocompatibility Testing
  • Humans
  • Infant
  • Infant Formula*
  • Infant, Newborn
  • Insulin-Secreting Cells / immunology*
  • Milk / immunology
  • Milk, Human
  • Pilot Projects


  • Autoantibodies
  • Biomarkers
  • Caseins
  • casein hydrolysate

Associated data