The New England journal of medicine
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In a prospective study to evaluate the prevalence and predictive potential of circulating islet-cell antibodies, we have screened 1723 "normal" first-degree relatives (parents, siblings, and offspring) of patients with insulin-dependent diabetes mellitus. The prevalence of islet-cell antibodies on initial screening was 0.9 per cent (16 of 1723). ⋯ In addition, 6 of 12 nondiabetic relatives with islet-cell antibodies had abnormally low insulin responses--below the third percentile in 6 and below the first percentile in 4--on their initial intravenous glucose challenge. Thus, prospective islet-cell antibody screening of high-risk first-degree relatives, in combination with intravenous glucose-tolerance testing, is capable of identifying immunologically abnormal persons with profoundly diminished beta-cell function, who are presumably at increased risk of insulin-dependent diabetes mellitus.
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After the death of a 12-year old girl with newly discovered insulin-dependent diabetes mellitus, we used monoclonal antibodies in an effort to identify the cells invading the pancreas. The majority of infiltrating lymphocytes were of the T cytotoxic/suppressor phenotype, but other T-cell subpopulations were present. Some of the T cells were "activated" (positive for HLA-DR antigen, and the interleukin-2 receptor). ⋯ Increased expression of Class I (HLA-A, B, and C) molecules was observed in the affected islet cells, and in damaged islets showing scant lymphocytic infiltration, some beta cells (still producing insulin), but not glucagon or somatostatin cells, were HLA-DR positive. The capillary endothelium was markedly dilated and strongly HLA-DR positive. These findings may contribute to an understanding of the sequence of events leading to the destruction of beta cells in classic Type I diabetes mellitus.