Enterovirus infections have been connected to type 1 diabetes. In the present study the possible role of intrauterine enterovirus infection as a risk factor for type 1 diabetes was evaluated. In addition, the epidemiology of enterovirus infections and herd immunity to enteroviruses was analysed in different populations to study their correlations with the risk of type 1 diabetes in these populations. The possible role of first trimester enterovirus infection was studied in 1162 mothers, whose child later presented with type 1 diabetes and an equal number of control mothers by analysing enterovirus IgG and IgM class antibodies using EIA. Serum samples for virus analyses were taken at the end of the first trimester of pregnancy. In another series enterovirus infections were analysed during the whole period of pregnancy in 70 mothers whose children developed type 1 diabetes and in 133 HLA matched control mothers. In this series, virus analyses were carried out from cord blood samples and samples taken at the end of the first trimester. In spite of the observed trend for slightly higher frequency of IgM class antibodies in case mothers than in control mothers, the results suggest that enterovirus infection during pregnancy is not a major risk factor for type 1 diabetes. The results suggest that enterovirus infection during pregnancy is not a major risk factor for type 1 diabetes in the child, but may play a role in some susceptible subjects. The epidemiology of enterovirus infections and type 1 diabetes was analysed in different countries in a randomly selected background population of infants (N=554), schoolchildren (N=887) and pregnant women (N=1176) by analysing enterovirus antibodies using EIA and plaque neutralisation assays. In order to assess the temporal trend in enterovirus infections, enterovirus antibodies were also measured from stored samples taken from pregnant women between 1983 and 2001 in Finland and Sweden (N=1999) and schoolchildren between the years 1975 and 2002 (N=438) in Finland. Enterovirus antibodies were less frequent in countries with a high incidence of type 1 diabetes (Finland and Sweden) compared to low incidence countries (Estonia, Germany, Hungary, Israel, Lithuania and the Karelian Republic of Russia). This difference was observed in all age groups. In addition, a linear decrease was observed in maternal enterovirus antibody levels over the past 20 years in Finland and Sweden. The results suggest that enterovirus infections are not particularly common in countries with high diabetes incidence. In contrast, there seems to be an inverse correlation between the incidence of type 1 diabetes and enterovirus infections in the background population. Accordingly, a new hypothesis (the polio hypothesis) was generated proposing that a low frequency of enterovirus infections in the background population increases the susceptibility of young children to the diabetogenic effect of enteroviruses. Collectively, the results suggest that enterovirus infections during pregnancy are not a major cause of type 1 diabetes in children, but may play a role in a subgroup of patients. In addition, there seems to be an inverse relationship between the frequency of enterovirus infections and type 1 diabetes in the background population, leading to a hypothesis that weak herd immunity to enteroviruses and low protection of infants by maternal antibodies may increase the risk of type 1 diabetes and contribute to the increasing incidence of type 1 diabetes.
