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

Diabetes Care. 2019 Feb;42(2):192-199. doi: 10.2337/dc18-0288. Epub 2018 Jul 30.

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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Adolescent
  • Adult
  • Autoantibodies / analysis
  • Autoantibodies / blood
  • Autoimmunity / genetics
  • Autoimmunity / physiology*
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1* / diagnosis
  • Diabetes Mellitus, Type 1* / epidemiology
  • Diabetes Mellitus, Type 1* / genetics
  • Diabetes Mellitus, Type 1* / prevention & control
  • Disease Progression
  • Diseases in Twins / diagnosis
  • Diseases in Twins / epidemiology
  • Diseases in Twins / genetics
  • Diseases in Twins / immunology
  • Environment
  • Female
  • Genetic Predisposition to Disease
  • Glutamate Decarboxylase / immunology
  • Humans
  • Insulin / metabolism
  • Islets of Langerhans / immunology*
  • Male
  • Mass Screening / methods
  • Risk Factors
  • Seroepidemiologic Studies
  • Siblings
  • Twins / genetics
  • Twins, Dizygotic* / genetics
  • Twins, Dizygotic* / statistics & numerical data
  • Twins, Monozygotic* / genetics
  • Twins, Monozygotic* / statistics & numerical data
  • Young Adult

Substances

  • Autoantibodies
  • Insulin
  • Glutamate Decarboxylase