Antibodies to oxidized insulin improve prediction of type 1 diabetes in children with positive standard islet autoantibodies

Diabetes Metab Res Rev. 2019 May;35(4):e3132. doi: 10.1002/dmrr.3132. Epub 2019 Feb 18.

Abstract

Background: Antibodies to posttranslationally modified insulin (oxPTM-INS-Ab) are a novel biomarker of type 1 diabetes (T1D). Here, we evaluated whether oxPTM-INS-Ab can improve T1D prediction in children with positive standard islet autoantibodies (AAB).

Methods: We evaluated sensitivity, specificity, accuracy, and risk for progression to T1D associated with oxPTM-INS-Ab and the standard islet AAB that include insulin (IAA), GAD (GADA), and tyrosine phosphatase 2 (IA-2A) in a cohort of islet AAB-positive (AAB+ ) children from the general population (median follow-up 8.8 years).

Results: oxPTM-INS-Ab was the most sensitive and specific autoantibody biomarker (74% sensitivity, 91% specificity), followed by IA-2A (71% sensitivity, 91% specificity). GADA and IAA showed lower sensitivity (65% and 50%, respectively) and specificity (66% and 68%, respectively). Accuracy (AUC of ROC) of oxPTM-INS-Ab was higher than GADA and IAA (P = 0.003 and P = 0.017, respectively), and similar to IA-2A (P = 0.896). oxPTM-INS-Ab and IA-2A were more effective than IAA for detecting progr-T1D when used as second-line biomarker in GADA+ children. Risk for diabetes was higher (P = 0.03) among multiple AAB+ who were also oxPTM-INS-Ab+ compared with those who were oxPTM-INS-Ab- . Importantly, when replacing IAA with oxPTM-INS-Ab, diabetes risk increased to 100% in children with oxPTM-INS-Ab+ in combination with GADA+ and IA-2A+ , compared with 84.37% in those with IAA+ , GADA+ , and IA-2A+ (P = 0.04).

Conclusions: Antibodies to oxidized insulin (oxPTM-INS-Ab), compared with IAA which measure autoantibodies to native insulin, improve T1D risk assessment and prediction accuracy in AAB+ children.

Keywords: biomarker; insulin autoantibodies; posttranslational modifications; prediction; type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Biomarkers / blood*
  • Blood Glucose / analysis
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / diagnosis*
  • Diabetes Mellitus, Type 1 / immunology
  • Female
  • Follow-Up Studies
  • Humans
  • Insulin Antibodies / immunology*
  • Insulin, Regular, Human / chemistry*
  • Insulin, Regular, Human / immunology*
  • Islets of Langerhans / immunology*
  • Longitudinal Studies
  • Male
  • Oxidation-Reduction
  • Prognosis
  • Prospective Studies
  • Protein Processing, Post-Translational

Substances

  • Autoantibodies
  • Biomarkers
  • Blood Glucose
  • Insulin Antibodies
  • Insulin, Regular, Human