Interaction of early cow's milk-based formula exposure and enterovirus infection in infancy in the development of type 1 diabetes-associated autoimmunity

Abstract

<p>Background Enteral virus infections and early introduction of cow’s milk<br />(CM)-based formula are among the suggested triggers of type 1 diabetes<br />(T1D)-associated autoimmunity, although studies on their role have remained<br />contradictory. Here, we aimed to analyse whether interactions between these<br />factors might clarify the controversies.<br />Materials The study population comprised 107 subjects developing positivity<br />for at least two T1D-associated autoantibodies and 446 control subjects from<br />the Finnish diabetes prediction and prevention cohort. Enterovirus, rotavirus,<br />adenovirus, respiratory syncytial virus and bovine insulin-binding antibodies<br />were analysed from prospective serum samples at 3–24 months of age. Data<br />on infant cow’s milk exposurewere available for 472 subjects: 251 subjects were<br />exposed to cow’s milk before 3 months of age and 221 subjects later in infancy.<br />Results Signs of an enterovirus infection by 12 months of age were<br />associated with the appearance of autoimmunity among children who were<br />exposed to cow’s milk before 3 months of age. Cox regression analysis revealed<br />a combined effect of enterovirus infection and early cow’s milk exposure for<br />the development of ICA and any of the biochemically defined autoantibodies<br />(p=0.001), of IAA (p=0.002), GADA (p=0.001) and IA-2A (p=0.013).<br />Conclusions The effect of enterovirus infection on the appearance of<br />T1D-associated autoimmunity seems to be modified by exposure to cow’s milk<br />in early infancy suggesting an interaction between these factors. Moreover,<br />these results provide an explanation for the controversial findings obtained<br />when analysing the effect of any single one of these factors on the appearance<br />of T1D-associated autoimmunity.<br /></p>