Timing of initial cereal exposure in infancy and risk of islet autoimmunity

JAMA. 2003 Oct 1;290(13):1713-20. doi: 10.1001/jama.290.13.1713.


Context: Dietary exposures in infancy have been implicated, albeit inconsistently, in the etiology of type 1 diabetes mellitus (DM).

Objective: To examine the association between cereal exposures in the infant diet and appearance of islet autoimmunity (IA).

Design: Birth cohort study conducted from 1994 to 2002 with a mean follow-up of 4 years.

Setting: Newborn screening for HLA was done at St Joseph's Hospital in Denver, Colo. First-degree relatives of type 1 DM individuals were recruited from the Denver metropolitan area.

Participants: We enrolled 1183 children at increased type 1 DM risk, defined as either HLA genotype or having a first-degree relative with type 1 DM, at birth and followed them prospectively. We obtained exposure and outcome measures for 76% of enrolled children. Participants had variable lengths of follow-up (9 months to 9 years).

Main outcome measures: Blood draws for the detection of insulin autoantibody, glutamic acid decarboxylase autoantibody, or IA-2 autoantibody were performed at 9, 15, and 24 months and annually thereafter. Children with IA (n = 34) were defined as those testing positive for at least 1 of the autoantibodies on 2 or more consecutive visits and who tested positive or had diabetes on their most recent visit.

Results: Children initially exposed to cereals between ages 0 and 3 months (hazard ratio [HR], 4.32; 95% confidence interval [CI], 2.0-9.35) and those who were exposed at 7 months or older (HR, 5.36; 95% CI, 2.08-13.8) had increased hazard of IA compared with those who were exposed during the fourth through sixth month, after adjustment for HLA genotype, family history of type 1 DM, ethnicity, and maternal age. In children who were positive for the HLA-DRB1*03/04,DQB8 genotype, adjusted HRs were 5.55 (95% CI, 1.92-16.03) and 12.53 (95% CI, 3.19-49.23) for initial cereal exposure between ages 0 to 3 months and at 7 months or older, respectively.

Conclusion: There may be a window of exposure to cereals in infancy outside which initial exposure increases IA risk in susceptible children.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoantibodies / blood*
  • Autoimmunity*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / epidemiology*
  • Diabetes Mellitus, Type 1 / etiology
  • Diabetes Mellitus, Type 1 / genetics
  • Edible Grain*
  • Genetic Predisposition to Disease
  • Genotype
  • Glutamate Decarboxylase / immunology
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Humans
  • Infant
  • Infant Food
  • Infant Nutritional Physiological Phenomena / physiology*
  • Infant, Newborn
  • Insulin Antibodies / blood
  • Islets of Langerhans / immunology*
  • Milk
  • Proportional Hazards Models
  • Risk Factors
  • Time Factors


  • Autoantibodies
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • ICA512 autoantibody
  • Insulin Antibodies
  • Glutamate Decarboxylase