Screening Strategy for Islet Autoantibodies in Diabetes Patients of Different Ages

Background: The detection of islet autoantibodies is essential for the accurate classification and diagnosis of diabetes mellitus (DM). The islet autoantibody distribution varies by age. However, screening strategies for DM patients with different onset ages remain lacking. Materials and Methods: This cross-sectional study included 17,536 DM patients from 46 medical centers across China. The seroprevalence of glutamic acid decarboxylase autoantibody (GADA), insulinoma-associated-2 autoantibody (IA-2A), zinc transporter 8 autoantibody (ZnT8A), and insulin autoantibody (IAA) was determined in younger and older patients with type 1 DM (T1DM) (n = 287 and 285, respectively), younger and older patients with latent autoimmune diabetes (LAD) (n = 140 and 121, respectively), and younger and older patients with type 2 DM (n = 200 in each group). Results: The cutoff age between younger and older patients was 35 years using restricted cubic spline method (n = 17,536, adjusted R2 = 0.97, residual standard error = 1.32; P < 0.001). The seroprevalence rates of four islet autoantibodies were higher in patients aged 15-35 years than in those ≥35 years (GADA: 17% vs. 5.6%, IA-2A: 8.5% vs. 1.3%, ZnT8A: 6.3% vs. 2.3%, IAA: 2.2% vs. 1.0%). The prevalence of ZnT8A was higher in LAD patients than in T1DM patients, especially in older LAD patients. The results indicated that ZnT8A detection can increase the detection rate of older LAD patients from 70.2% (based on GADA detection alone) to 91.7%. Conclusions: In patients stratified according to the cutoff age of 35 years, the optimal detection sequence should be GADA, IA-2A, and ZnT8A in younger patients and GADA, ZnT8A, and IA-2A in older patients, so as to reduce the screening cost while improving the detection rate. Particularly, the ZnT8A test is recommended in older patients to avoid a missed LAD diagnosis.