MON-550 - Retrospective Analysis of Islet Autoantibody Dynamics: A Seven-Year National Reference Laboratory Study

Introduction: Islet autoantibodies against glutamic acid decarboxylase (GAD), islet tyrosine phosphatase 2 (IA-2), zinc transporter 8 (ZnT8), and insulin (IAA) are standard biomarkers for predicting Type 1 Diabetes (T1D) progression. Characterizing features such as age at seroconversion, sequence of emergence, and antibody expansion is vital for understanding the heterogeneous nature of T1D. Our large-scale reference laboratory database provides an opportunity to better capture the differing phenotypes across diverse pediatric and adult populations on a national scale.

Objective: To characterize longitudinal islet autoantibody dynamics in a large U.S. population undergoing serial testing from 2018 to 2025.

Methods: A retrospective analysis of GAD, IA-2, ZnT8, and IAA positivity measured by immunoassays was conducted at Labcorp endocrine specialty lab. From an initial 2018–2019 cohort of 148,005 autoantibody-positive patients, we identified individuals who were initially single-antibody positive and underwent serial testing through 2025. Seroconversion was defined as positive results for the same antibody on at least 2 occasions within 12 months; reversion was defined as negative results on at least 2 occasions within 12 months. C-peptide trends were assessed in patients with ≥1positive autoantibodies.

Results: Of the 148,005 patients, 1,964 met the criteria for initial single-antibody positivity and serial follow-up testing. Within this group, seroconversion occurred in 75 adults and 14 pediatric patients (age < 18 yrs). GAD and IAA were the most prevalent antibodies in both cohorts. A subset of adults with autoantibody seroconversion demonstrated autoantibody expansion, consistently following a GAD to IAA sequence. Antibody reversion was found in 12 adults and 2 pediatric patients. In the multi-antibody positive patients, over 50% of individuals showed stable c-peptide levels regardless of the degree of antibody positivity.

Conclusion: Our findings align with prospective longitudinal studies while potentially reflecting at-risk populations in community settings. Interpretation of c-peptide levels may be confounded by treatment effect, which is a major limitation of our study due to lack of access to in-depth clinical data.

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