Genetics of type 1 diabetes mellitus

Diabetes mellitus in children, adolescents and young adults results from targeted immune-mediated destruction of the pancreatic P-cells in the islets of Langerhans in the pancreas. Its onset can be as early as in the first year of life; the peak incidence is during puberty, but it can also become manifest in old age. The vast majority of patients have no family history of type 1 diabetes (>85%), whilst up to 15% of first-degree relatives are affected by the same disease. Although this is predominantly a sporadic disease, nearly all patients have a genetic susceptibility conferred by genes in the HLA region on chromosome 6p, by alleles at the insulin gene locus (chromosome 11) and by the gene coding for the cytotoxicT-lymphocyte antigen 4 (CTLA4, chromesome 2). It is hoped that over 2500 families in which 2 or more siblings have type 1 diabetes (multiplex families) can be recruited for current international studies, so that the predisposing genes can be more precisely identified. At present the genetic data can only be interpreted at the epidemiological level and cannot be used to predict type 1 diabetes. However, investigation of patients' antibody profiles in combination with gene typing of several genes and analysis of P-cell function makes it possible to narrow down the individual risk.