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Doyle, D. Walker, H. Catte, M. Dean, B. Drury-Brown, M.M.C. Hackman, S. Lee, K. Malkani, K. Cullen, P. Johnson, M. Hampton, C. McCarrell, E. Curtis, Paul, Y. Zambrano

There are variable reports of risk of concordance for progression to islet autoantibodies (Ab+) and type 1 diabetes in identical twins (IT) after one twin is diagnosed. We examined development of Ab+ and type 1 diabetes and the effects of genetic factors and common environment on Ab+ in IT, nonidentical twins (NT), and full siblings (FS). Subjects from the TrialNet Pathway to Prevention Study (N = 48,026) were screened from 2004 to 2015 for Ab+ (GAD antibody [GADA], insulinoma-associated antigen 2 [IA-2A], and autoantibodies against insulin [IAA]). Of these, 17,226 (157 IT, 283 NT, and 16,786 FS) were followed for Ab+ or type 1 diabetes for a median of 2.1 years. At screening, IT were more likely to have positive GADA, IA-2A, and IAA than NT or FS (all P < 0.0001). Younger age, male sex, and genetic factors were significant factors for expression of IA-2A, IAA, one or more Ab+, and two or more Ab+ (all P ≤ 0.03). Initially, Ab+ IT had a 69% risk of diabetes by 3 years compared with 1.5% for initially autoantibody negative (b-) IT. In NT, type 1 diabetes risk by 3 years was 72% for initially multiple Ab+, 13% for single Ab+, and 0% for initially Ab- NT. FS had a 3-year type 1 diabetes risk of 47% for multiple Ab+, 12% for single Ab+, and 0.5% for initially Ab- subjects. Risk of type 1 diabetes at 3 years is high for initially multiple and single Ab+ IT and multiple Ab+ NT. Genetic predisposition, age, and male sex are significant risk factors for development of Ab+ in twins.