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Anette-G. Ziegler, MD; Sandra Schmid, PhD; Doris Huber; Michael Hummel, MD; Ezio Bonifacio, PhD

JAMA. 2003;290:1721-1728.

Context  Dietary factors modifying type 1 diabetes mellitus (DM) risk have been proposed, but little is known if they trigger the islet autoimmunity that precedes clinical disease.

Objective  To determine whether breastfeeding duration, food supplementation, or age at introduction of gluten-containing foods influences the risk of developing islet autoantibodies.

Design and Setting  Prospective natural history cohort study conducted from 1989 to 2003 in inpatient/outpatient clinics in Germany.

Participants  The BABYDIAB study follows newborn children of parents with type 1 DM. Eligibility requirements were met in 1610 children. Blood samples were obtained at birth, age 9 months, 2, 5, and 8 years. Dropout rate was 14.4% by age 5 years. Breastfeeding data were obtained by prospective questionnaires (91% complete), and food supplementation data were obtained by family interview (72% for food supplementation and 80% for age of gluten introduction).

Main Outcome Measure  Development of islet autoantibodies (insulin, glutamic acid decarboxylase, or IA-2 antibodies) in 2 consecutive blood samples.

Results  Life-table islet autoantibody frequency was 5.8% (SE, 0.6%) by age 5 years. Reduced total or exclusive breastfeeding duration did not significantly increase the risk of developing islet autoantibodies. Food supplementation with gluten-containing foods before age 3 months, however, was associated with significantly increased islet autoantibody risk (adjusted hazard ratio, 4.0; 95% confidence interval, 1.4-11.5; P = .01 vs children who received only breast milk until age 3 months). Four of 17 children who received gluten foods before age 3 months developed islet autoantibodies (life-table 5-year risk, 24%; SE, 10%). All 4 children had the high-risk DRB1*03/04,DQB1*0302 genotype. Early exposure to gluten did not significantly increase the risk of developing celiac disease–associated autoantibodies. Children who first received gluten foods after age 6 months did not have increased risks for islet or celiac disease autoantibodies.

Conclusion  Ensuring compliance to infant feeding guidelines is a possible way to reduce the risk of development of type 1 DM autoantibodies.

Author Affiliations: Diabetes Research Institute and Hospital München-Schwabing, Munich, Germany (Drs Ziegler, Schmid, and Hummel, and Ms Huber) and Istituto Scientifico San Raffaele, Milan, Italy (Dr Bonifacio).

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