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Pediatr Diabetes. 2019 Jan 10. doi: 10.1111/pedi.12812. [Epub ahead of print]

Predicting progression to type 1 diabetes from ages 3 to 6 in islet autoantibody positive TEDDY children.

Author information

1
Department of Pediatrics, University of Florida, Gainesville, Florida.
2
Department of Clinical Sciences Malmö, Lund University, Skåne University Hospital SUS, Malmö, Sweden.
3
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, Florida.
4
Division of Endocrinology, University of Miami, Miami, Florida.
5
Pacific Northwest Diabetes Research Institute, Seattle, Washington.
6
Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia.
7
Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver, Colorado.
8
Department of Pediatrics, Turku University Hospital, Turku, Finland.
9
Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
10
Department of Pediatrics, Medical Research Center, PEDEGO Research Unit, Oulu University Hospital and University of Oulu, Oulu, Finland.
11
Institute of Diabetes Research, Helmholtz Zentrum München and Forschergruppe Diabetes e.V. Neuherberg, Neuherberg, Germany.
12
Division of Diabetes, Endocrinology, and Metabolism, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.

Abstract

OBJECTIVE:

The capacity to precisely predict progression to type 1 diabetes (T1D) in young children over a short time span is an unmet need. We sought to develop a risk algorithm to predict progression in children with high-risk human leukocyte antigen (HLA) genes followed in The Environmental Determinants of Diabetes in the Young (TEDDY) study.

METHODS:

Logistic regression and 4-fold cross-validation examined 38 candidate predictors of risk from clinical, immunologic, metabolic, and genetic data. TEDDY subjects with at least one persistent, confirmed autoantibody at age 3 were analyzed with progression to T1D by age 6 serving as the primary endpoint. The logistic regression prediction model was compared to two non-statistical predictors, multiple autoantibody status, and presence of insulinoma-associated-2 autoantibodies (IA-2A).

RESULTS:

A total of 363 subjects had at least one autoantibody at age 3. Twenty-one percent of subjects developed T1D by age 6. Logistic regression modeling identified 5 significant predictors - IA-2A status, hemoglobin A1c, body mass index Z-score, single-nucleotide polymorphism rs12708716_G, and a combination marker of autoantibody number plus fasting insulin level. The logistic model yielded a receiver operating characteristic area under the curve (AUC) of 0.80, higher than the two other predictors; however, the differences in AUC, sensitivity, and specificity were small across models.

CONCLUSIONS:

This study highlights the application of precision medicine techniques to predict progression to diabetes over a 3-year window in TEDDY subjects. This multifaceted model provides preliminary improvement in prediction over simpler prediction tools. Additional tools are needed to maximize the predictive value of these approaches.

KEYWORDS:

autoantibodies; metabolic; pediatric; prediction; type 1 diabetes

PMID:
30628751
DOI:
10.1111/pedi.12812

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