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