Comprehensive Diabetes Autoantibody Laboratory-Based Clinical Service Testing in 6044 Consecutive Patients: Analysis of Age and Sex Effects

Background: In 2017, Mayo Clinic Laboratories commenced offering a comprehensive type 1 diabetes mellitus (T1DM) autoantibody (Ab) evaluation including 4 known Abs targeting glutamic acid decarboxylase (GAD65), protein tyrosine phosphatase-like islet antigen 2 (IA2), insulin (IAA), and zinc transporter 8 protein (ZnT8) antigens. Methods: The objective of this study was to evaluate real-time data on the frequency and patterns of all 4 Abs stratified by age and sex from 6044 unique consecutive adult and pediatric patients undergoing evaluation for suspected diabetes. Results: At least one Ab was found in 3370 (56%) of all samples: 67% of children (aged 0-17), 49% of young adults (aged 18-35), and 41% for both middle-aged (aged 36-55) and older (aged >55) adults (P ≤ 0.0001). GAD65-Abs were the most common in all age groups, followed by ZnT8-Ab in those <36 years, or IAA-Ab in those ≥36. Frequencies of IA2- and ZnT8-Abs drop significantly with increasing age. Clusters of 3 or 4 Abs were more frequently encountered in younger patients (41% of children vs 12% in middle- and 13% in older age groups, P ≤ 0.0001). Conclusions: Children undergoing serological evaluation for T1DM were more commonly positive for autoantibodies than older age groups. The frequency of ZnT8- and IA2-Abs decreases, and IAA-Ab frequency increases with increasing age, and clusters of 2 to 4 autoantibodies are more common in children. In clinical practice, comprehensive testing for diabetes autoantibodies resulted in a switch in diagnosis to T1DM for patients previously classified as type 2 diabetes mellitus.