Islet cell antibodies in individuals at increased risk for IDDM

Islet cell cytoplasmic antibodies (ICA), islet cell surface ( ICSA ) antibodies, HLA phenotypes, glucose tolerance, insulin secretion, and insulin sensitivity were studied in 16 twins of insulin-dependent diabetics as well as in 21 subjects with impaired glucose tolerance (IGT). 60% of the identical twins and 40% of the non-identical twins were ICSA -positive. The prevalence of ICSA in control persons was only 5%. ICA were found in all identical twins and in half of the non-identical twins. However, ICSA and ICA results were concordant in only 46% of the whole group of twins. There was no correlation between ICSA and either insulin secretion or insulin sensitivity. In the IGT subjects exhibiting low and normal insulin responses ICSA were observed in 67% and 23%, respectively. A high proportion of twins, but not of IGT subjects, had HLA DR3 or DR4 antigens which seem to confer genetic susceptibility to the development of IDDM. In the majority of DR3/DR4 twins, ICSA were also present. This might support the hypothesis of genetically-based autoimmunity, although the precise relationship between HLA and islet cell antibodies has to be clarified in a prospective study.