Non-genetic risk determinants of type 1 diabetes.

A low concordance rate of Type 1 diabetes among monozygotic twins clearly indicate that genetic risk factors may be necessary but are not sufficient for the disease to occur. Descriptive epidemiological studies from all over the world have disclosed clear age, sex seasonal and geographical variability of the disease occurrence and also increasing incidence rates by time within countries and among migrant groups indicating that several different non-genetic risk factors are of importance for the etiology of Type 1 diabetes. Analytical epidemiological studies have further indicated exposures that are associated with an increased risk for the disease. Thus, early fetal events such as exposure to viruses and maternal blood-group incompatibility may be non-genetic risk factors associated with the initiation of auto-immunity in the genetically susceptible child. Further, early exposure to cow's milk protein and a high frequency of intake of nitrosamine-rich food may act as initiating events. Other risk determinants such as a high growth rate, exposure to many infectious diseases, a cold environment and stressful life events may promote an already ongoing autoimmune destructive process causing and increased work load on the beta-cell or through induction of lymphokine release. The diversity of risk determinants that are associated with Type 1 diabetes risk points at a complex interaction between the genome and environment and multivariate analyses have disclosed different risk profiles in different age groups. Further epidemiological and experimental studies are necessary to disclose the causal relationship and the mechanism of action of the non-genetic risk determinants to provide a basis for primary prevention in the general population.