Differential Diagnostic Utilities Of Combined Testing For Islet Cell Antibody, Glutamic Acid Decarboxylase Antibody, And Tyrosine Phosphatase Antibody

BACKGROUND. Beta-cell antibody tests are used for the differential diagnosis of diabetes mellitus. They permit to discriminate between the type 1 diabetes (T1D) and non-autoimmune diabetes types. To choose an appropriate test for ruling in or ruling out the T1D a physician needs to know how conclusive test results are. The most powerful estimate of test conclusiveness is its likelihood ratio (LHR). The higher LHR of a positive result (LHR+), the more posttest probability of T1D; the lower LHR of a negative result (LHR-), the less posttest probability of T1D.AIMS. To compare conclusiveness of single and combined tests for antibodies to islet cells (ICA), glutamate decarboxylase (GADA), and tyrosine phosphatase IA-2 (IA-2A), and to evaluate posttest probabilities of T1D at various pretest probabilities.METHODS. All antibodies were tested in parallel in 169 children and adolescents with a new-onset T1D, and in 169 persons without this disease. ICA, GADA, and IA-2A were determined by indirect immunofluorescence, radioimmune assay, and ELISA, respectively. LHR+ and LHR-were calculated with the MedCalc Statistical Software. Posttest T1D probabilities were calculated from Bayes theorem-based equation.RESULTS. Among single tests, an ICA test had the greatest LHR+ and the smallest LHR-, and consequently was the most reliable either for ruling in or ruling out the T1D. Among test combinations, an ICA&GADA combination had the greatest LHR+ and was the most suitable for T1D confirmation. The triple combination ICA&GADA&IA-2A had the smallest LHR- and was the most suitable for T1D exclusion.CONCLUSIONS. In the differential diagnosis of diabetes, the most appropriate test for ruling in the T1D is the double combination ICA&GADA. With both antibodies positive, this combination provides the highest posttest T1D probabilities at any pretest probability. The most appropriate test for ruling out the T1D is the triple combination ICA&GADA&IA-2A. With all three antibodies negative, this combination provides the lowest posttest T1D probabilities.