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Jill M. Norris, MPH, PhD; Katherine Barriga, MSPH; Georgeanna Klingensmith, MD; Michelle Hoffman, RN; George S. Eisenbarth, MD, PhD; Henry A. Erlich, MD, PhD; Marian Rewers, MD, PhD

JAMA. 2003;290:1713-1720.

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.

Author Affiliations: Department of Preventive Medicine and Biometrics (Dr Norris, Mss Barriga and Hoffman) and Barbara Davis Center for Childhood Diabetes (Drs Klingensmith, Eisenbarth, and Rewers), University of Colorado Health Sciences Center, Denver; Department of Human Genetics, Roche Molecular Systems Inc, Alameda, Calif (Dr Erlich).

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