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Predicting Diabetes Using Genetic Risk Scores

Identical and Nonidentical Twins: Risk and Factors Involved in Development of Islet Autoimmunity and Type 1 Diabetes

  1. Taylor M. Triolo1,
  2. Alexandra Fouts1,
  3. Laura Pyle2,
  4. Liping Yu1,
  5. Peter A. Gottlieb1,
  6. Andrea K. Steck1, and
  7. the Type 1 Diabetes TrialNet Study Group*
    1. 1Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO
    2. 2Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO
    1. Corresponding author: Taylor M. Triolo, taylor.triolo{at}childrenscolorado.org
    Diabetes Care 2019 Feb; 42(2): 192-199. https://doi.org/10.2337/dc18-0288
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    Abstract

    OBJECTIVE There are variable reports of risk of concordance for progression to islet autoantibodies and type 1 diabetes in identical twins after one twin is diagnosed. We examined development of positive autoantibodies and type 1 diabetes and the effects of genetic factors and common environment on autoantibody positivity in identical twins, nonidentical twins, and full siblings.

    RESEARCH DESIGN AND METHODS Subjects from the TrialNet Pathway to Prevention Study (N = 48,026) were screened from 2004 to 2015 for islet autoantibodies (GAD antibody [GADA], insulinoma-associated antigen 2 [IA-2A], and autoantibodies against insulin [IAA]). Of these subjects, 17,226 (157 identical twins, 283 nonidentical twins, and 16,786 full siblings) were followed for autoantibody positivity or type 1 diabetes for a median of 2.1 years.

    RESULTS At screening, identical twins were more likely to have positive GADA, IA-2A, and IAA than nonidentical twins or full siblings (all P < 0.0001). Younger age, male sex, and genetic factors were significant factors for expression of IA-2A, IAA, one or more positive autoantibodies, and two or more positive autoantibodies (all P ≤ 0.03). Initially autoantibody-positive identical twins had a 69% risk of diabetes by 3 years compared with 1.5% for initially autoantibody-negative identical twins. In nonidentical twins, type 1 diabetes risk by 3 years was 72% for initially multiple autoantibody–positive, 13% for single autoantibody–positive, and 0% for initially autoantibody-negative nonidentical twins. Full siblings had a 3-year type 1 diabetes risk of 47% for multiple autoantibody–positive, 12% for single autoantibody–positive, and 0.5% for initially autoantibody-negative subjects.

    CONCLUSIONS Risk of type 1 diabetes at 3 years is high for initially multiple and single autoantibody–positive identical twins and multiple autoantibody–positive nonidentical twins. Genetic predisposition, age, and male sex are significant risk factors for development of positive autoantibodies in twins.

    Footnotes

    • This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0288/-/DC1.

    • ↵* A complete list of the Type 1 Diabetes TrialNet Study Group can be found in the Supplementary Data online.

    • See accompanying articles, pp. 189, 200, 208, 215, and e16.

    • Received February 7, 2018.
    • Accepted June 28, 2018.
    • © 2018 by the American Diabetes Association.
    http://www.diabetesjournals.org/content/license

    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.

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    Diabetes Care: 42 (2)

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    Identical and Nonidentical Twins: Risk and Factors Involved in Development of Islet Autoimmunity and Type 1 Diabetes
    Taylor M. Triolo, Alexandra Fouts, Laura Pyle, Liping Yu, Peter A. Gottlieb, Andrea K. Steck, the Type 1 Diabetes TrialNet Study Group
    Diabetes Care Feb 2019, 42 (2) 192-199; DOI: 10.2337/dc18-0288

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    Identical and Nonidentical Twins: Risk and Factors Involved in Development of Islet Autoimmunity and Type 1 Diabetes
    Taylor M. Triolo, Alexandra Fouts, Laura Pyle, Liping Yu, Peter A. Gottlieb, Andrea K. Steck, the Type 1 Diabetes TrialNet Study Group
    Diabetes Care Feb 2019, 42 (2) 192-199; DOI: 10.2337/dc18-0288
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    © 2019 by the American Diabetes Association. Diabetes Care Print ISSN: 0149-5992, Online ISSN: 1935-5548.