Signs of beta-cell autoimmunity in nondiabetic schoolchildren: a comparison between Russian Karelia with a low incidence of type 1 diabetes and Finland with a high incidence rate.

OBJECTIVE: We sought to study the prevalence of autoantibodies to various islet cell antigens in the background population of two neighboring countries with a sixfold difference in the incidence of type 1 diabetes. RESEARCH DESIGN AND METHODS: Serum samples were obtained from 3,652 nondiabetic schoolchildren in Finland and from 1,988 schoolchildren in the adjacent Karelian Republic of Russia. The Karelian children were divided into three groups (Finns/Karelians, Russians, and others) based on the ethnic background of their mother. The samples were analyzed for islet cell antibodies (ICAs), insulin autoantibodies (IAAs), GAD antibodies (GADAs), and the tyrosine phosphatase-like insulinoma antigen 2 (IA-2A) protein and HLA class II genotypes. RESULTS: The frequency of ICAs, IAAs, and GADAs did not differ significantly between the Karelian (3.5, 0.6, and 0.9%, respectively) and Finnish children (2.8, 0.9, and 0.5%, respectively). Similarly, the frequency of multiple (> or = 2) autoantibodies was similar in both countries (0.5 vs. 0.6%). The frequency of IA-2A was, however, four times higher in Finland (0.6 vs. 0.15% in Russian Karelia; P = 0.03). There were no significant differences in autoantibody prevalence among the three ethnic groups in Russian Karelia. There was a falling frequency of GADAs and of positivity for multiple autoantibodies along with decreasing HLA-conferred disease susceptibility among the Finnish schoolchildren. CONCLUSIONS: These data indicate that beta-cell autoimmunity among schoolchildren is as frequent in Russian Karelia as in Finland, although the incidence of clinical type 1 diabetes is six times higher in Finland. However, in contrast to this general trend, IA-2As were more common in Finland. Since IA-2As usually appear late in the preclinical process, this suggests that progressive beta-cell autoimmunity is more rare in Russian Karelia.

A six-fold gradient in the incidence of type 1 diabetes at the eastern border of Finland.

OBJECTIVE: Type 1 diabetes results from gene-environment interactions in subjects with genetic susceptibility to the disease. We assessed the contribution of environmental and genetic factors to type 1 diabetes by comparing the incidence in two neighboring populations living in conspicuously different socioeconomic circumstances. RESEARCH DESIGN AND METHODS: We compared the incidence over a 10-year period (1990-99) in children younger than 15 years of age living in the Karelian Republic of Russia and in Finland. The frequency of susceptible and protective human leukocyte antigen (HLA)-DQ alleles was analyzed in 400 non-diabetic schoolchildren from Russian Karelia and 1000 Finnish subjects. RESULTS: The average annual age-adjusted incidence of type 1 diabetes was lower in Russian Karelia than in Finland: 7.4 per 100000 (95% confidence interval 3.5-11.3) versus 41.4 per 100000 (37.3-45.5), while there were no differences in the frequency of the HLA DQ genotypes predisposing to type 1 diabetes in the background populations. The incidence rate did not differ significantly between different ethnic groups in Russian Karelia (Finns/Karelians, Russians, others). CONCLUSIONS: There is a close to six-fold gradient in the incidence of type 1 diabetes between Russian Karelia and Finland, although the predisposing HLA DQ genotypes are equally frequent in the two populations. This suggests that environmental factors contribute to this steep difference in the incidence rate between these adjacent regions.

Relationship between the incidence of type 1 diabetes and enterovirus infections in different European populations: results from the EPIVIR project.

The incidence of type 1 diabetes varies markedly between countries. As enterovirus infections have been linked to type 1 diabetes, we determined whether this variation correlates with the frequency of enterovirus infections in different Caucasian populations in Europe. Enterovirus antibodies were examined in the background population (1-year-old and 10-14-year-old children) in seven countries with either exceptionally high (Finland and Sweden) or low/intermediate incidence of diabetes (Estonia, Germany, Hungary, Lithuania, Russia) using EIA and neutralisation assays. Enterovirus antibodies were less frequent in countries with high diabetes incidence compared to countries with low diabetes incidence (P<0.001). This suggests 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, which is in line with the previously proposed polio hypothesis according to which the complications of enterovirus infections become more common in an environment with a decreased rate of infections.