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Diabetes Metab Res Rev. 2019 Jan 29:e3132. doi: 10.1002/dmrr.3132. [Epub ahead of print]

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

Author information

1
Department of Medicine, Unit of Endocrinology & Diabetes, Universitá Campus Bio-Medico di Roma, Rome, Italy.
2
Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
3
I.R.C.C.S. Istituto Ortopedico Galeazzi, Milan, Italy.
4
Division of Pediatrics, Department of Clinical Experimental Medicine, Medical Faculty, Linköping University, Linköping, Sweden.
5
Centre for Immunobiology, the Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
6
Crown Princess Victoria Children's Hospital, Region Östergötland, Linköping, Sweden.

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

PMID:
30693639
DOI:
10.1002/dmrr.3132

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