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. 2019 May;20(3):263-270.
doi: 10.1111/pedi.12812. Epub 2019 Jan 29.

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

Laura M Jacobsen  1 , Helena E Larsson  2 , Roy N Tamura  3 , Kendra Vehik  3 , Joanna Clasen  3 , Jay Sosenko  4 , William A Hagopian  5 , Jin-Xiong She  6 , Andrea K Steck  7 , Marian Rewers  7 , Olli Simell  8 , Jorma Toppari  8   9 , Riitta Veijola  10 , Anette G Ziegler  11 , Jeffrey P Krischer  3 , Beena Akolkar  12 , Michael J Haller  1 ; TEDDY Study Group
Affiliations

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

Laura M Jacobsen et al. Pediatr Diabetes. 2019 May.

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.

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Conflict of interest statement

The authors have no relevant conflicts of interest to disclose.

Figures

Figure 1:
Figure 1:
Flowchart of Children Enrolled in Cohort for Analysis.
See this image and copyright information in PMC

References

    1. Ziegler AG, Rewers M, Simell O, Simell T, Lempainen J, Steck A, Winkler C, Ilonen J, Veijola R, Knip M, Bonifacio E, Eisenbarth GS. Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA. 2013. June 19;309(23):2473–9. - PMC - PubMed
    1. Steck AK, Vehik K, Bonifacio E, Lernmark A, Ziegler AG, Hagopian WA, She J, Simell O, Akolkar B, Krischer J, Schatz D, Rewers MJ; TEDDY Study Group. Predictors of Progression From the Appearance of Islet Autoantibodies to Early Childhood Diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY). Diabetes Care. 2015. May;38(5):808–13. - PMC - PubMed
    1. Orban T, Sosenko JM, Cuthbertson D, Krischer JP, Skyler JS, Jackson R, Yu L, Palmer JP, Schatz D, Eisenbarth G; Diabetes Prevention Trial-Type 1 Study Group. Pancreatic islet autoantibodies as predictors of type 1 diabetes in the Diabetes Prevention Trial-Type 1. Diabetes Care. 2009. December;32(12):2269–74. - PMC - PubMed
    1. Sosenko JM, Krischer JP, Palmer JP, Mahon J, Cowie C, Greenbaum CJ, Cuthbertson D, Lachin JM, Sklyer JS, The Diabetes Prevention Trial- Type 1 Study Group. A risk score for Type 1 diabetes derived from autoantibody-positive participants in the diabetes prevention trial-Type 1. Diabetes Care. 2008; 31, 528–533. - PubMed
    1. TEDDY Study Group. The Environmental Determinants of Diabetes in the Young (TEDDY) Study. Ann N Y Acad Sci. 2008; 1150:1–13. - PMC - PubMed

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