Assay Are the Earliest Indicator of Prediabetic Islet Autoimmunity

OBJECTIVEdWe evaluated a novel electrochemiluminescent assay for insulin/proinsulin autoantibodies (ECL-IAA) as a new marker of the onset of islet autoimmunity and as a predictor of type 1 diabetes. RESEARCHDESIGNANDMETHODSdTheDiabetes Autoimmunity Study in the Young (DAISY) prospectively follows children at increased genetic risk for development of islet autoim-munity (defined as presence of autoantibodies to insulin, glutamic acid decarboxylase [GAD65], IA-2, or zinc transporter 8 [ZnT8]) and type 1 diabetes (general population of children and first-degree relatives). Serial serum samples from subjects whoprogressed to type 1 diabetes andwho had their first islet autoantibodies measured by age 18 months (N = 47) were tested using ECL-IAA. RESULTSdAlmost all prediabetic children tested positive for ECL-IAA (46 of 47, 98%) during follow-up. ECL-IAAwas almost always the first autoantibody to appear (94 % total; 21 % very first [by itself]; 23 % with only mIAA; 19 % with another islet autoantibody [GAD or ZnT8]; and 30% with$2 other antibodies [mIAA, GAD, IA-2, or ZnT8]). Among the 46 subjects who were ECL-IAA–positive, ECL-IAA antedated the onset of other islet autoantibodies by a mean of 2.3 years (range, 0.3–7.2 years). Both the age of appearance of autoantibody and IAA levels (but no