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Differential diagnostic utilities of combined testing for islet cell antibody, glutamic acid decarboxylase antibody, and tyrosine phosphatase antibody

https://doi.org/10.14341/DM9364

Abstract

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.

About the Authors

Alexei V. Timofeev

Pirogov Russian National Research Medical University; Morozov Children's Municipal Clinical Hospital of the Moscow City Health Department


Russian Federation

PhD in Biology



Igor E. Koltunov

Morozov Children's Municipal Clinical Hospital of the Moscow City Health Department


Russian Federation

MD, Professor



Elena E. Petriaikina

Morozov Children's Municipal Clinical Hospital of the Moscow City Health Department


Russian Federation

MD



Irina G. Rybkina

Morozov Children's Municipal Clinical Hospital of the Moscow City Health Department


Russian Federation


Lubov N. Samsonova

Russian Medical Academy of Continuous Professional Education


Russian Federation

MD, Professor



Anatoly N. Tiulpakov

Endocrinology Research Centre


Russian Federation

MD, Professor



Natalia A. Zubkova

Endocrinology Research Centre


Russian Federation

MD



Irina G. Kolomina

Bashliaeva Children's Municipal Clinical Hospital of the Moscow City Health Department


Russian Federation


Evgenia A. Evsjukova

Bashliaeva Children's Municipal Clinical Hospital of the Moscow City Health Department


Russian Federation


Sergey S. Bukin

Bashliaeva Children's Municipal Clinical Hospital of the Moscow City Health Department


Russian Federation


Alexey C. Khrushchev

Pirogov Russian National Research Medical University


Russian Federation


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Supplementary files

1. Рисунок к статье Тимофеева и соавт 2017_09_28
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Type Исследовательские инструменты
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2. SUPPLEMENT 1. Demographic and laboratory characteristics of the subjects and inclusion criteria in the study
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3. SUPPLEMENT 1. Demographic and laboratory characteristics of the subjects and inclusion criteria in the study
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4. SUPPLEMENT 2. Operational parameters of single antobody tests and their combinations
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5. SUPPLEMENT 2. Operational parameters of single antobody tests and their combinations
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6. SUPPLEMENT 3. The comparison of characteristical curves for antobody tests
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7. SUPPLEMENT 3. The comparison of characteristical curves for antobody tests
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8. SUPPLEMENT 4. Post-test probabilities of type 1 DM with different pre-test probabilities of type 1 DM and with various results of antidody tests with confidence intervals
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9. SUPPLEMENT 4. Post-test probabilities of type 1 DM with different pre-test probabilities of type 1 DM and with various results of antidody tests with confidence intervals
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10. SUPPLEMENT 5. Fagan's nomogram for the approximate evaluation of post-test probabilities of type 1 DM with known likelihood ratios for the antibody tests
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11. SUPPLEMENT 5. Fagan's nomogram for the approximate evaluation of post-test probabilities of type 1 DM with known likelihood ratios for the antibody tests
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Review

For citations:


Timofeev A.V., Koltunov I.E., Petriaikina E.E., Rybkina I.G., Samsonova L.N., Tiulpakov A.N., Zubkova N.A., Kolomina I.G., Evsjukova E.A., Bukin S.S., Khrushchev A.C. Differential diagnostic utilities of combined testing for islet cell antibody, glutamic acid decarboxylase antibody, and tyrosine phosphatase antibody. Diabetes mellitus. 2018;21(2):74-83. https://doi.org/10.14341/DM9364

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ISSN 2072-0351 (Print)
ISSN 2072-0378 (Online)