Significance of cow's milk protein antibodies as risk factor for childhood IDDM: interactions with dietary cow's milk intake and HLA-DQB1 genotype

Abstract

Dietary factors are suspected to play an aetiological role in the development of insulin-dependent diabetes mellitus (IDDM). We analysed cow's milk formula, betalactoglobulin, and bovine serum albumin antibodies by an enzyme-linked immunoassay in unselected children with newly diagnosed IDDM and in their non-diabetic siblings and inquired about infant feeding practices by questionnaire. Among 410 diabetic sibling pairs matched for age and sex, by logistic regression analysis - including overall duration of breast-feeding, age at introduction of dairy products, recent consumption of cow's milk and HLA-DQB1 genotype ("high/moderate" vs "low/decreased" risk of IDDM) - bovine serum albumin IgG antibody levels (OR 2.12, 95% CI 1.25-3.57) and genetic risk (OR 3.81, 95% CI 2.43-5.17) were positively associated with IDDM; cow's milk formula IgM antibodies were inversely associated with the risk of IDDM (OR 0.50, 95% CI 0.29-0.87). Of the diabetic sibling pairs, 42 were identical for HLA-DQB1 alleles associated with IDDM risk or protection (DQB1*0201, *0301, *0302 and *0602/03). In these 42 pairs, children with IDDM had higher median levels of bovine serum albumin IgG, of betalactoglobulin IgG, and of cow's milk formula IgG and IgA antibodies than the non-diabetic siblings (p < 0.05). In conclusion, children with IDDM have higher levels of cow's milk protein antibodies than their HLA-DQB1-matched sibling controls, and these high levels of antibodies are independent risk markers for IDDM.