Bivalent GAD autoantibody ELISA improves clinical utility and risk prediction for adult autoimmune diabetes

Abstract Aim/Introduction To investigate the differences in the clinical significance and glutamic acid decarboxylase autoantibody (GADA) affinity between RIA (RIA‐GADA) and ELISA (ELISA‐GADA) in patients with type 1 diabetes. Methods A total of 415 patients with type 1 diabetes were enrolled, including 199 acute‐onset type 1 diabetes, 168 slowly progressive type 1 diabetes (SPIDDM), and 48 fulminant type 1 diabetes. GADA affinity was measured by a competitive binding experiment using unlabeled recombinant human GAD65 protein, and the diagnostic performance of both assays and the relationship between GADA affinity and the decline of fasting C‐peptide (F‐CPR) were examined. Results While the ELISA‐GADA displayed a higher sensitivity than the RIA method in diagnosing type 1 diabetes in acute‐onset patients, about 40% of SPIDDM patients with low‐titer RIA‐GADA were determined as negative by the ELISA method. Patients with type 1 diabetes with RIA‐GADA alone had an older age of onset, less diabetic ketoacidosis, a higher BMI, and a higher F‐CPR compared with patients positive for both RIA‐GADA and ELISA‐GADA. Additionally, 36% of RIA‐GADA‐positive patients had low‐affinity GADA (