The requirements of prospective studies of natural history of the disease in infancy are different from those of risk assessment, and it is desirable to include all autoantibody markers in the primary test. Risk of type 1 diabetes is strongly associated with the number of antibodies found to have raised levels, and only individuals with elevated levels of two or more markers should be considered as being at high risk. Individuals found to have elevated levels of one or more of the antibodies included in the primary test should therefore be further evaluated by measurement of other markers to quantify risk more precisely. Results of antibody testing in any laboratory should be interpreted in light of the sensitivity and specificity of the assays in newly diagnosed type 1 diabetes. Participation in workshop or proficiency programs that allow laboratories to determine these parameters is strongly recommended.
Genetic testing is of limited value in family members in whom autoantibody levels are known.
However, HLA class II typing may be useful in identifying infants for prospective follow-up for the appearance of islet autoantibodies or for recruitment into trials of interventions aimed at prevention of the initiation of autoimmunity. Metabolic testing with evaluation of the FPIR in an intravenous glucose tolerance test can be used to identify the subgroup of individuals with elevated levels of multiple antibodies who are at the greatest risk of progression to diabetes in the short term. Individuals with multiple islet antibodies in whom FPIR is preserved are, however, at high risk for delayed development of diabetes, and clinical onset may occur up to at least 20 years after first antibody detection. Preliminary results suggest that detection of multiple antibodies in individuals from the general population is associated with increased risk, but the number of individuals studied prospectively is currently insufficient to allow quantification of risk. G.S.E. is a consultant for Quest Diagnostics.