AN INCREASED LEVEL OF ANTIBODIES TO BETA-LACTOGLOBULIN IS A RISK DETERMINANT FOR EARLY-ONSET TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS INDEPENDENT OF ISLET CELL ANTIBODIES AND EARLY INTRODUCTION OF COWS MILK

Using a case-control design we have studied whether antibodies to cow's milk proteins are risk determinants for childhood-onset Type 1 (insulin-dependent) diabetes mellitus independent of early exposure to cow's milk formula and islet cell antibodies. Sera from 116 recent-onset diabetic children and 112 age- and sex- matched control children were analysed for cow's milk protein IgA, IgG and IgM antibodies. Beta-lactoglobulin IgA and IgM antibodies and islet cell antibodies. The titres were compared to questionnaire data on duration of breast-feeding and introduction of formula feeding. Most antibody levels tended to be increased among diabetic compared to control children. This was statistically significant for cow's milk protein IgA antibodies (p < 0.001) and beta-lactoglobulin IgA antibodies (p < 0.01) as well as for islet cell antibody-positivity which was found among 92 % of the diabetic and 3 % of control children. The differences in cow's milk protein antibodies as well as beta-lactoglobulin antibodies were more pronounced among children with an early onset of Type 1 diabetes. Breast-feeding duration was significantly inversely related to the log of beta-lactoglobulin IgG (r = -0.16, p = 0.04) and the log of cow's milk protein IgA antibodies (r = -0.17. p < 0.001). A positive correlation was found between formula feeding and the logarithm of beta-lactoglobulin IgG antibodies (r = 0.22, p = 0.01) and the log of cow's milk protein IgA antibodies (r = 0.16, p = 0.04). In a multiple logistic regression analysis it was found that IgA antibodies to beta-lactoglobulin and cow's milk protein were significantly related to the risk of Type 1 diabetes independent of islet cell antibodies. When introducing formula feeding before the age of 4 months as a variable in the regression it was shown that islet cell antibodies and beta-lactoglobulin IgA antibodies were still significantly and independently related to an increased risk of diabetes whereas cow's milk protein IgA antibodies did not add further to the regression. It is concluded that beta-lactoglobulin IgA antibodies are significantly associated with an increased risk of diabetes at a young age independent of islet cell antibody-status and of an early weaning to cow's milk formula. In genetically susceptible children early exposure to beta-lactoglobulin might be one trigger in the autoimmune process leading to development of Type 1 diabetes.