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Islet Autoantibody Type-Specific Titer Thresholds Improve Stratification of Risk of Progression to Type 1 Diabetes in Children

Overview
Journal Diabetes Care
Specialty Endocrinology
Date 2021 Nov 11
PMID 34758977
Citations 9
Authors
Affiliations
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Abstract

Objective: To use islet autoantibody titers to improve the estimation of future type 1 diabetes risk in children.

Research Design And Methods: Prospective cohort studies in Finland, Germany, Sweden, and the U.S. followed 24,662 children at increased genetic or familial risk to develop islet autoimmunity and diabetes. For 1,604 children with confirmed positivity, titers of autoantibodies against insulin (IAA), GAD antibodies (GADA), and insulinoma-associated antigen 2 (IA-2A) were harmonized for diabetes risk analyses.

Results: Survival analysis from time of confirmed positivity revealed markedly different 5-year diabetes risks associated with IAA (n = 909), GADA (n = 1,076), and IA-2A (n = 714), when stratified by quartiles of titer, ranging from 19% (GADA 1st quartile) to 60% (IA-2A 4th quartile). The minimum titer associated with a maximum difference in 5-year risk differed for each autoantibody, corresponding to the 58.6th, 52.4th, and 10.2nd percentile of children specifically positive for each of IAA, GADA, and IA-2A, respectively. Using these autoantibody type-specific titer thresholds in the 1,481 children with all autoantibodies tested, the 5-year risk conferred by single (n = 954) and multiple (n = 527) autoantibodies could be stratified from 6 to 75% (P < 0.0001). The thresholds effectively identified children with a ≥50% 5-year risk when considering age-specific autoantibody screening (57-65% positive predictive value and 56-74% sensitivity for ages 1-5 years). Multivariable analysis confirmed the significance of associations between the three autoantibody titers and diabetes risk, informing a childhood risk surveillance strategy.

Conclusions: This study defined islet autoantibody type-specific titer thresholds that significantly improved type 1 diabetes risk stratification in children.

Citing Articles

Consensus Guidance for Monitoring Individuals With Islet Autoantibody-Positive Pre-Stage 3 Type 1 Diabetes.

Phillip M, Achenbach P, Addala A, Albanese-ONeill A, Battelino T, Bell K Diabetes Care. 2024; 47(8):1276-1298.

PMID: 38912694 PMC: 11381572. DOI: 10.2337/dci24-0042.


Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes.

Phillip M, Achenbach P, Addala A, Albanese-ONeill A, Battelino T, Bell K Diabetologia. 2024; 67(9):1731-1759.

PMID: 38910151 PMC: 11410955. DOI: 10.1007/s00125-024-06205-5.


Islet autoantibodies as precision diagnostic tools to characterize heterogeneity in type 1 diabetes: a systematic review.

Felton J, Redondo M, Oram R, Speake C, Long S, Onengut-Gumuscu S Commun Med (Lond). 2024; 4(1):66.

PMID: 38582818 PMC: 10998887. DOI: 10.1038/s43856-024-00478-y.


Understanding Islet Autoantibodies in Prediction of Type 1 Diabetes.

Jia X, Yu L J Endocr Soc. 2024; 8(1):bvad160.

PMID: 38169963 PMC: 10758755. DOI: 10.1210/jendso/bvad160.


Refining the Definition of Stage 1 Type 1 Diabetes: An Ontology-Driven Analysis of the Heterogeneity of Multiple Islet Autoimmunity.

Frohnert B, Ghalwash M, Li Y, Ng K, Dunne J, Lundgren M Diabetes Care. 2023; 46(10):1753-1761.

PMID: 36862942 PMC: 10516254. DOI: 10.2337/dc22-1960.


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