Epitope-specific GAD65Abs and HLA-DR-DQ gene assays help improve the value of risk stratification in autoimmune diabetes mellitus and protect islet function. Identification and early intervention are important for latent autoimmune diabetes in youth (LADY). The aims of this study were to investigate 1) the frequencies of the epitope-specific GAD65Abs and HLA-DR-DQ genes in LADY and 2) the association between HLA-DR-DQ genes and epitope-specific GAD65Abs. Higher frequencies of GAD65-CAb and multiepitope GAD65Abs were observed in young type 1 diabetes, LADY, and old type 1 diabetes subjects than those in latent autoimmune diabetes in adult (LADA) patients. The frequencies of the specific susceptible HLA haplotype DR3, total susceptible HLA haplotypes, and high-risk genotypes were higher in type 1 diabetes and LADY patients than those in LADA patients. In contrast, type 1 diabetes and LADY patients had lower frequencies of low/no genetic risk genotypes (DRX/X) than those of LADA patients. Logistic regression analysis suggested that the susceptible HLA haplotypes were risk factors for glutamic acid decarboxylase antibody (GADA) multiepitope positivity in autoimmune diabetes mellitus. LADY may be more severe than LADA, and LADY seemed to be a transitional type of type 1 diabetes and LADA. GADA epitope and HLA-DR-DQ gene assays are important for risk stratification in autoimmune diabetes mellitus and protection of islet function.
Aims This study investigated insulinoma‐associated‐2 autoantibody (IA‐2A) and zinc transporter 8 autoantibody (ZnT8A) distribution in patients with type 1 diabetes (T1D) and latent autoimmune diabetes (LAD) and the autoantibodies' association with clinical characteristics and HLA‐DR‐DQ genes. Materials and Methods This cross‐sectional study recruited 17,536 patients with diabetes from 46 hospitals across China. A total of 189 patients with T1D and 58 patients with LAD with IA‐2A positivity, 126 patients with T1D and 86 patients with LAD with ZnT8A positivity, and 231 patients with type 2 diabetes (T2D) were selected to evaluate islet autoantibodies, clinical phenotypes, and HLA‐DR‐DQ gene frequency. Results IA‐2A was bimodally distributed in patients with T1D and LAD. Patients with low IA‐2A titre LAD had lower fasting C‐peptide (FCP) (p < 0.01), lower postprandial C‐peptide (PCP) (p < 0.001), and higher haemoglobin A1c (HbA1c) levels (p < 0.05) than patients with T2D. Patients with high IA‐2A titre LAD were younger than patients with low IA‐2A titre LAD (p < 0.05). Patients with low IA‐2A titre T1D had lower FCP (p < 0.01), lower PCP (p < 0.01), and higher HbA1c levels (p < 0.05) than patients with high IA‐2A titre LAD. HLA‐DR‐DQ genetic analysis demonstrated that the frequency of susceptible HLA haplotypes was higher in IA‐2A‐positive patients (p < 0.001) than in patients with T2D. Patients with high ZnT8A titre LAD had lower FCP (p = 0.045), lower PCP (p = 0.023), and higher HbA1c levels (p = 0.009) and a higher frequency of total susceptible haplotypes (p < 0.001) than patients with low ZnT8A titre LAD. Conclusions IA‐2A in patients with T1D and LAD was bimodally distributed, and the presence of IA‐2A could demonstrate partial LAD clinical characteristics. ZnT8A titre had a certain predictive value for islet functions in patients with LAD.
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