Positive Autoantibody Results 

All islet autoantibody-based risk estimates for progression
to Stage 3 T1D are based on confirmed islet autoantibody
positivity. Therefore, confirmation testing in a second
sample is a critical step to establish persistent islet
autoimmunity and to provide accurate risk
communication and determination of stage of T1D.  

        Following positive screening results, a confirmatory visit should be scheduled to collect another blood sample and repeat islet autoantibody testing using a highly specific autoantibody assay method. While the assay used for screening and confirmation may often be the same, i.e., have the same sensitivity and specificity, data has shown that overall specificity of the confirmed result can be increased by using a different assay from the screening assay. (see Module 5). Further, confirmation testing in a venous sample is recommended in order to reduce the likelihood of assay interference caused by hemolysis. 

 

Identifying Higher-Risk Individuals for Expedited Follow-Up 

The timing of the confirmation visit should be triaged according to the risk of rapid or imminent progression to Stage 3 T1D.(1-3) Ideally, those who report symptoms at screening should have had HbA1c testing at that time. People with a risk of rapid progression should be prioritized for a prompt return visit; this group includes those who report symptoms (polyuria, polydipsia weight loss, fatigue etc.) and/or have an elevated HbA1c (≥ 5.7%) or multiple positive autoantibodies at screening. The pace of progression from asymptomatic T1D to symptomatic, Stage 3 T1D is inversely related to age of onset of islet autoimmunity. Consequently, the younger the child (<5 yrs. of age) the more quickly they should be seen. Conversely, older individuals or those with a single autoantibody at screening may indicate a lower-risk status. Irrespective of risk status, confirmatory testing is still important to plan for appropriate monitoring and follow-up.

 

Testing to Confirm Positive Islet Autoantibody Results  

To confirm one or more positive islet autoantibody results, a second blood sample should be collected by venipuncture.(4)

• For individuals with higher risk (symptomatic, elevated HbA1c or positive for multiple autoantibodies), confirmatory testing should be performed  within 1-2 months  of the initial screening.

• For individuals with a relatively lower risk, confirmatory testing should be completed  within 3-6 months of initial screening.

Confirmation should include testing for all four islet autoantibodies (GADA, IAA, IA2A, ZnT8A) at a CLIA-certified laboratory, ideally with an assay that meets IASP standards.(5) 

 

Data from the Autoimmunity Screening for Kids (ASK) program shows positive confirmatory testing rates:

        • 94% for multiple autoantibody positivity at screening 

        • 93% for single autoantibody positivity by a highly specific screening method. (see Module 5).   

        • 75% for a single positive autoantibody at screening by radio-binding assay (RBA) methodology. 

 

Additional Testing at Confirmatory Visit 

Tests/evaluation to be conducted:(1)  

        • HbA1c to evaluate recent blood glucose trends over the last 3 months.
           (Note: rapid evolution of dysglycemia may be missed with this test.) 

        • Random blood glucose measures (fasting or non-fasting) for real-time measurement.  

        • Evaluation for symptoms of hyperglycemia (polyuria, polydipsia, weight loss, lethargy, etc.). 

The individual/family should be educated about typical signs and symptoms of Stage 3 T1D. If there is concern regarding current symptoms, the individual/family can be instructed on how to use a glucometer
to monitor blood glucose (see Module 9: Monitoring and Managing Islet Autoantibody Positive Persons).