Cow's milk formula feeding induces primary immunization to insulin in infants at genetic risk for type 1 diabetes

Insulin autoantibodies (IAAs) often appear as the first sign of islet cell autoimmunity in prediabetic children, Because cow's milk contains bovine in sulin, we followed the development of insulin-binding antibodies in childre n fed with cow's milk formula. Bovine insulin- and human insulin-binding an tibodies by enzyme immunoassay and IAA by radioimmunoassay were analyzed in 200 infants carrying HLA-DQB1*0302 but no protective alleles who participa ted in a Finnish population-based birth-cohort study. Based on the prospect ively registered information, the first 100 infants enrolled in the study w ho Were exposed to cow's milk formula before age 12 weeks and the first 100 infants enrolled in the study who were exclusively breast-fed for longer t han their first 12 weeks of life were selected for the present study. Also, 11 children from the birth cohort who developed at least two diabetes-asso ciated autoantibodies, 98 children with newly diagnosed type 1 diabetes, an d 92 healthy children were studied. We found that the amount of IgG-antibod ies binding to bovine insulin was higher at age 3 months in infants who wer e exposed to cow's milk formula than in infants who were exclusively breast -fed at that age (median 0.521 vs. 0.190; P < 0.0001), The antibodies bindi ng to bovine insulin cross-reacted with human insulin. None of these infant s tested positive for IAA, The levels of bovine insulin-binding antibodies declined in both groups at ages 12 and 18 months, whereas in the 11 childre n with at least two diabetes-associated autoantibodies the levels increased during the followup period (P < 0.0001), IgG antibodies correlated with Ig G2 antibodies binding to bovine insulin (r = 0.43, P = 0.004) and IAA (r = 0.27, P = 0.02) in diabetic children, but not in healthy children. Cow's mi lk feeding is an environmental trigger of immunity to insulin in infancy th at may explain the epidemiological link between the risk of type 1 diabetes and early exposure to cow's milk formulas, This immune response to insulin may later be diverted into autoaggressive immunity against beta-cells in s ome individuals, as indicated by our findings in children with diabetes-ass ociated autoantibodies.