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

• Published in: Diabetes care Vol. 36; no. 8; pp. 2266 - 2270
• Main Authors: LIPING YU, FRAN DONG, DONGMEI MIAO, FOUTS, Alexandra R, WENZLAU, Janet M, STECK, Andrea K
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-08-2013
• Subjects: Autoantibodies; Autoantibodies - blood; Autoimmunity; Biological and medical sciences; Cation Transport Proteins - immunology; Child, Preschool; Development and progression; Diabetes; Diabetes Mellitus, Type 1 - immunology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Glutamate Decarboxylase - immunology; Humans; Immune system; Infant; Insulin; Insulin Antibodies - blood; Islets of Langerhans - immunology; Luminescent Measurements; Medical sciences; Metabolic diseases; Miscellaneous; Original Research; Prediabetic state; Prediabetic State - diagnosis; Prediabetic State - immunology; Proinsulin - immunology; Prospective Studies; Public health. Hygiene; Public health. Hygiene-occupational medicine; Sensitivity and Specificity; Type 1 diabetes; Zinc Transporter 8; Colorado; Autoimmunity; Human; Proinsulin; Pancreatic hormone; Nutrition; Antibody; Langerhans islet; Autoantibody; Metabolic diseases; Prohormone; Insulin; Indicator; Assay; Endocrinology; Endocrine pancreas
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc12-2245

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.
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.
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.
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.