title: Proinsulin/Insulin autoantibodies measured with electrochemiluminescent assay are the earliest indicator of prediabetic islet autoimmunity.
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.
  
  
  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, 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.
authors: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado, USA.
authors: Liping
authors: L
authors: Yu
authors: Fran
authors: F
authors: Dong
authors: Dongmei
authors: D
authors: Miao
authors: Alexandra R
authors: AR
authors: Fouts
authors: Janet M
authors: JM
authors: Wenzlau
authors: Andrea K
authors: AK
authors: Steck
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D027682:Cation Transport Proteins / Q000276:immunology; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007223:Infant; D007330:Insulin Antibodies / Q000097:blood*; D007515:Islets of Langerhans / Q000276:immunology*; D008163:Luminescent Measurements; D011236:Prediabetic State / Q000175:diagnosis / Q000276:immunology*; D011384:Proinsulin / Q000276:immunology*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D000075703:Zinc Transporter 8
chemical_list: D001323:Autoantibodies; D027682:Cation Transport Proteins; D007330:Insulin Antibodies; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; D011384:Proinsulin; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2