Why do children get diabetes? : A study on some genetical, immunological and environmental factors

Sammanfattning: Insulin dependent diabetes mellitus (IDDM) is one of the most common and serious chronic disorders of childhood. Despite advances in the knowledge about the cause of IDDM during the last decades the etiology still remains incompletely understood but is probably due to a complex network of genetic, immunological and environmental factors. The aim of the thesis was to elucidate some parts of this network and, if possible, identify riskfactors or markers for the development of IDDM in childhood.Background infonnation was received from questionnaires and/or medical records. Islet cell surface antibodies (ICSA) were analysed by a new radioimmunologic method with a specificity of 100 % and a sensitivity of 70 % for positive titers, while the other autoantibodies and C-peptide values were determined by wellknown and accepted methods.An international study on 745 HLA-typed children with diabetes indicated that IDDM is genetically heterogenous. Patients with HLA-DR3/nonDR4 generally have a milder form of diabetes than patients without this marker.Studies from the South-east region of Sweden showed that early weight gain seems to be more correlated to development of IDDM than breastfeeding resp. non-breastfeeding.Analysis of space-time clustering in all cases of childhood diabetes (n=584) diagnosed between 1977-1990 indicates clustering with maximal effect within 7 months and 15 km. The frequency of islet cell antibodies (!CA) among non-diabetic schoolchildren was 1,4 %. Corresponding figures for insulinautoantibodies) IAA) and ICSA were 4,0 % and 4,3 %respectively. Only !CA showed a relationship to C-peptide values. Children with low levels of ICA had high values and vice versa.An international family study showed that certain factors seem to cause not only a high incidence of diabetes in Finland and Sweden but also a more aggressive early disease process. ICSA was the only  autoantibody which showed simultaneous positivity in all family members. ICSA had also a similar seasonality as incidence of IDDM and was most common in family members of patients with a short duration of symptoms before diagnosis (<8 days).In conclusion, early feeding may be of importance for future development of Type I diabetes not only because of degree of exposition to cow milk proteins but also because of effects on energy intake and early betacellstimulation. Environmental factors, probably infections, are of importance for eliciting the disease. High incidence areas have a moreaggressive disease process than areas with lower incidence. Although signs on an autoimmune attack on the beta cells are rather common in the general population such an attack seldom leads to IDDM. ICSA, contrary to ICA, may reflect an early ongoing disease process in genetically predisposed individuals.