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

Triolo TM, Fouts A, Pyle L, Yu L, Gottlieb PA, Steck AK, Type 1 Diabetes TrialNet Study Group
Diabetes Care. 2019 42 (2): 192-199

PMID: 30061316 · PMCID: PMC6341285 · DOI:10.2337/dc18-0288

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 ( = 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 < 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 ≤ 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.

© 2018 by the American Diabetes Association.

MeSH Terms (25)

Adolescent Adult Autoantibodies Autoimmunity Child Child, Preschool Diabetes Mellitus, Type 1 Disease Progression Diseases in Twins Environment Female Genetic Predisposition to Disease Glutamate Decarboxylase Humans Insulin Islets of Langerhans Male Mass Screening Risk Factors Seroepidemiologic Studies Siblings Twins Twins, Dizygotic Twins, Monozygotic Young Adult

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