Aims: It is important to differentiate the two major phenotypes of adult-onset diabetes, autoimmune type 1 diabetes (T1D) and non-autoimmune type 2 diabetes (T2D). Serum GAD65 autoantibodies (GADA) are the most sensitive biomarker for adult-onset autoimmune T1D, but the clinical value of GADA by current standard radio-binding assays (RBA) remains questionable. The present study focused on the clinical utility of GADA differentiated by a new electrochemiluminescence (ECL) assay in patients with adult-onset diabetes.
Methods: Two cohorts of individuals recently diagnosed with diabetes at ≥20 years of age were analyzed including 771 patients 30-70 years olds from the Action LADA study and 2,063 patients 20-45 year olds from the Diabetes in Young Adults (DiYA) study. Clinical characteristics including requirement of early insulin treatment, BMI, and development of multiple islet autoantibodies were analyzed according to the status of RBA-GADA and ECL-GADA, respectively.
Results: GADA was the most prevalent and predominant autoantibody, >90% in both cohorts with any positive autoantibody. GADA positivity by either RBA or ECL assay significantly discriminated clinical T1D from T2D. However, patients with ECL-GADA in both cohorts were at greatest risk of insulin treatment, multiple islet autoantibodies and lower BMI (all p<0.0001). Among patients GADA positive by RBA, 32.4% (90/278) in the Action LADA study and 25.6% (32/125) in the DiYA study were negative by ECL assay. Patients with GADA detectable by RBA, not confirmed by ECL, had a phenotype more similar to T2D and these RBA-GADA had lower affinity compared to GADA confirmed by ECL assay.
Conclusion: The ECL-GADA assay offers advantages over the RBA-GADA in identification of adult-onset diabetes patients at higher risk of early insulin dependency.
X. Jia: None. L. Yu: None. R. D. Leslie: None. The action lada consortium: n/a. The diabetes in young adults (diya) study group: n/a. Y. Gu: None. T. Vartak: None. D. Miao: None. F. Dong: None. S. T. Jerram: None. M. Rewers: Advisory Panel; Self; Provention Bio, Inc., Consultant; Self; RTI, Research Support; Self; Janssen Research & Development, LLC, JDRF. A. Ferrara: None. J. M. Lawrence: None.
JDRF (2-SRA-2019-695-S-B); National Institutes of Health (DK32083); 5th Framework Program of the European Union; Centers for Disease Control and Prevention (1U18DP006289)