Genetik, autoimmunphänomene und umweltfaktoren des prä-typ-1-diabetes: Die Deutsche multizenterstudie BABYDIAB

BABYDIAB is a prospective study in children whose parents have had type 1 diabetes since birth. This study commenced in 1989, and since then over 2000 children have been observed. At nine months, and at two, five, eight and eleven years of age, the children are monitored for four different islet auto-antibodies (ICA, IAA, GADA, IA2A), environmental factors and genetic risk factors (HLA DR, DQ, insulin gene polymorphism). Children from the age of two, regardless of HLA genotype, who are found to be positive for at least two islet auto-antibodies, have a 100% risk of acquiring type 1 diabetes before the age of 10. IgG insulin antibodies are usually the first to be detected, and consist mainly of IgG1 and IgG4 subtypes. Two different types of antibody were detected: a 'rapid' type, produced en masse within a matter of months, and a 'chronically progressive' type, showing a more steady and sequential build up. Genetic factors (excluding external factors such as breast-feeding and vaccination), are significantly associated with the appearance of islet autoimmunity. Twenty percent of children with the HLA genotypes DQB1*0201/0302 or DRB1*04/04, DQB1*0302/0302 develop islet auto-antibodies prior to the age of three, compared to 2.7% without these genotypes. The early appearance of the auto-immune process as seen in this study suggests that further, more detailed analyses of environmental factors and cellular immune markers should be integrated into future preventative studies.