Proinsulin/Insulin Autoantibodies Measured With Electrochemiluminescent Assay Are the Earliest Indicator of Prediabetic Islet Autoimmunity

  1. Andrea K. Steck, MD
  1. Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado
  1. Corresponding author: Andrea Steck, andrea.steck{at}ucdenver.edu

Abstract

OBJECTIVE We 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.

RESEARCH DESIGN AND METHODS The Diabetes Autoimmunity Study in the Young (DAISY) prospectively follows children at increased genetic risk for development of islet autoimmunity (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 who progressed to type 1 diabetes and who had their first islet autoantibodies measured by age 18 months (N = 47) were tested using ECL-IAA.

RESULTS Almost all prediabetic children tested positive for ECL-IAA (46 of 47, 98%) during follow-up. ECL-IAA was 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 not GAD65, IA2, or ZnT8 levels) are major determinants of the age of diabetes onset.

CONCLUSIONS This new ECL-IAA assay defines more precisely the onset of prediabetic autoimmunity and may help identify events triggering islet autoimmunity, as well as allow earlier intervention for type 1 diabetes. Nearly all young children progressing to diabetes are insulin autoantibody–positive.

  • Received October 31, 2012.
  • Accepted January 8, 2013.

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This Article

  1. Diabetes Care
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