Antibodies to post-translationally modified insulin as a novel biomarker for prediction of type 1 diabetes in children

Rocky Strollo, Chiara Vinci, Nicola Napoli, Paolo Pozzilli, Johnny Ludvigsson, Ahuva Nissim

Research output: Contribution to journalArticlepeer-review

Abstract

Aims/hypothesis: We have shown that autoimmunity to insulin in type 1 diabetes may result from neoepitopes induced by oxidative post-translational modifications (oxPTM). Antibodies specific to oxPTM-insulin (oxPTM-INS-Ab) are present in most newly diagnosed individuals with type 1 diabetes and are more common than autoantibodies to native insulin. In this study, we investigated whether oxPTM-INS-Ab are present before clinical onset of type 1 diabetes, and evaluated the ability of oxPTM-INS-Ab to identify children progressing to type 1 diabetes. Methods: We used serum samples collected longitudinally from the ‘All Babies in Southeast Sweden (ABIS)’ cohort tested for the gold standard islet autoantibodies to insulin (IAA), GAD (GADA), tyrosine phosphatase 2 (IA-2A) and zinc transporter 8 (ZnT8A). We studied 23 children who progressed to type 1 diabetes (progr-T1D) and 63 children who did not progress to type 1 diabetes (NP) after a median follow-up of 10.8 years (interquartile range 7.7–12.8). Of the latter group, 32 were positive for one or more islet autoantibodies (NP-AAB+). oxPTM-INS-Ab to insulin modified by OH or HOCl were measured by our developed ELISA platform. Results: Antibodies to at least one oxPTM-INS were present in 91.3% of progr-T1D children. oxPTM-INS-Ab co-existed with GADA, IA-2A, IAA or ZnT8A in 65.2%, 56.5%, 38.9% and 33.3% progr-T1D children, respectively. In addition, oxPTM-INS-Ab were present in 17.4%, 26.1%, 38.9% and 41.6% of progr-T1D children who were negative for GADA, IA-2A, IAA and ZnT8A, respectively. OH-INS-Ab were more common in progr-T1D children than in NP-AAB+ children (82.6% vs 19%; p < 0.001) and allowed discrimination between progr-T1D and NP-AAB+ children with 74% sensitivity and 91% specificity. None of the NP-AAB children were positive for oxPTM-INS-Ab. Conclusions/interpretation: oxPTM-INS-Ab are present before the clinical onset of type 1 diabetes and can identify children progressing to type 1 diabetes.

Original languageEnglish
Pages (from-to)1467-1474
Number of pages8
JournalDiabetologia
Volume60
Issue number8
DOIs
Publication statusPublished - Aug 1 2017

Keywords

  • Biomarker
  • Insulin
  • Insulin autoantibodies
  • Islet autoantibodies
  • Oxidative stress
  • Post-translational modifications
  • Type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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