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Age of First Cereal Exposure May Affect Appearance of Islet Autoimmunity in Infants At High Risk for Type 1 Diabetes Mellitus

Infants who are at high risk for developing type 1 diabetes mellitus (DM) are more likely to develop diabetes-associated autoantibodies if introduced to gluten-containing foods during their first 3 months of life, and show increased risk of islet autoimmunity when exposed to cereals between 1 and 3 months or at 7 months or older, say researchers.

These findings are the result of data from 2 separate studies conducted in Germany and the United States.

Anette-G. Ziegler, MD, Diabetes Research Institute, Munich, Germany and colleagues found that "exposure to dietary gluten before age 3 months showed a 5-fold higher risk for the development of islet autoantibodies than after age 3 months." The German investigators analysed blood samples obtained at birth, 9 months, and 2, 5, and 8 years of age from 1610 children of parents with type 1 DM, and they collected breastfeeding and food supplementation data by family interviews.

The cumulative risk of developing islet autoantibodies among all 1610 offspring was 5.8% by the age of 5 years. Overall, 85 offspring developed islet autoantibodies and of these 48 were positive for 2 or more islet autoantibodies. Type 1 DM developed in 22 offspring who were positive and none of those negative for the antibodies. The investigators report a reduced duration in total or exclusive breastfeeding did not significantly increase the risk of developing the antibodies.

However, the risk of developing islet autoantibodies was 24% in children who received gluten-containing foods during their first 3 months of life compared with a risk of 7% among children who were exclusively breast fed. Of the 17 children fed gluten-containing foods during their first 3 months, 4 developed islet autoantibodies and all of these children had the high-risk DRB1*03/04,DQB1*0302 genotype.

"These findings indicate that early introduction of gluten-containing foods should be avoided in children who are genetically predisposed to type 1 DM," Dr. Ziegler and colleagues conclude.

In the United States, lead investigator Jill M. Norris, MPH, PhD, University of Colorado Health Sciences Center, Denver, and colleagues obtained data on breastfeeding duration and time of first cereal exposure for 1149 infants unaffected and 34 infants affected with islet autoimmunity. Follow up ranged from 9 months to 9 years.

After adjusting for HLA genotype, family history of type 1 DM, ethnicity, and maternal age the investigators found that children initially exposed to cereals between 1 and 3 months of age had a 4.32 hazard ratio and those exposed to cereals when 7 months or older had a 5.36 hazard ratio of islet autoimmunity when compared with children exposed to cereals while 4 to 6 months of age. Among children positive for the HLA-DRB1*03/04,DQB8 genotype adjusted hazard ratios were 5.55 for initial cereal exposure between 1 and 3 months and 12.53 for initial exposure when 7 months or older compared with exposure between 4 and 6 months of age.

The adjusted hazard ratios were higher for the 1 to 3 months and the 7 months or older groups whether fed rice or gluten-containing cereals. However if cereals were introduced while the child was still breastfeeding the risk of islet autoimmunity was reduced and this reduction was independent of the child's age at initial cereal exposure.

"Our data suggest that introducing cereals before age 4 months may increase a child's risk of islet autoimmunity," Dr. Norris and colleagues write adding that "waiting until age 7 months or older to first introduce cereals also may increase the risk for islet autoimmunity." They conclude, "there may be a window of exposure to cereals in infancy outside which initial exposure increases islet autoimmunity risk in susceptible children."

JAMA 2003;290:13:1721-1728. "Early Infant Feeding and Risk of Developing Type 1 Diabetes–Associated Autoantibodies"

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