Proposed guidelines on screening for risk of type 1 diabetes.

T hese guidelines represent the recommendations of the Immunology of Diabetes Society (IDS) on the assessment of risk of type 1 diabetes in unaffected first-degree relatives of patients with the disease, and are based on the consensus reached at a symposium held at the fourth meeting of the IDS (Fiuggi, Italy, November 1999). Assessment of risk of type 1 diabetes in relatives was initially based on detection of circulating islet cell antibodies (ICAs) supplemented by measurement of insulin autoantibodies (IAAs), and evaluation of ␤-cell function by determination of the first-phase insulin response (FPIR) in the intravenous glucose tolerance test. Other islet autoantigens, including GAD and the protein tyrosine phosphatase IA-2/ICA512, have subsequently been identified, and the role of autoantibodies to these antigens in assessment of risk of type 1 diabetes in first-degree relatives has been investigated in a number of large prospective studies. In addition, the genetic susceptibility to type 1 diabetes, particularly that conferred by genes in the HLA class II region, has been more precisely defined, and alleles conferring both susceptibility for and protection from the disease have been identified. This offers the possibility of combining immune, metabolic, and genetic markers in strategies to identify family members at risk, with the hope that it will eventually be possible to intervene in such individuals to delay the clinical onset of type 1 diabetes either before or after the initiation of the autoimmune processes that result in ␤-cell destruction. While a number of intervention trials are ongoing, no agent has yet to be shown as effective in the prevention of type 1 diabetes. Therefore, the major indication for testing is to identify individuals at risk for inclusion in intervention trials or prospective studies of the natural history of autoim-mune diabetes. RECOMMENDATIONS — Screening for immune or genetic markers of risk of type 1 diabetes should usually be under-taken only in the context of defined research studies. Testing for antibodies to GAD and/or IA-2 or for GAD antibodies and/or IAA using sensitive radiobinding assays can identify Ͼ85% of cases of newly diagnosed or future type 1 diabetes with 98% speci-ficity. It is therefore recommended that, as a minimum, primary testing to identify relatives at increased risk should include measurement of levels of antibodies to GAD with either IAAs or antibodies to IA-2. The appearance of IAAs may precede that of antibodies to GAD and/or IA-2, and IAAs may be the only …