Correspondence

Concordance for Islet Autoimmunity among Monozygotic Twins

N Engl J Med 2008; 359:2849-2850December 25, 2008

Article

To the Editor:

The risk of type 1 diabetes among the monozygotic twins of patients with type 1 diabetes is reported to be as low as 30%; this percentage is usually based on the ascertainment of data at a single time point.1-3 Less is known about the cumulative incidence of islet antibodies and diabetes among twins followed over time.4,5 We analyzed the long-term risk of islet autoimmunity and type 1 diabetes in a cohort of twins of patients with type 1A diabetes as defined by the American Diabetes Association criteria (95% of the twins with a prediabetic condition who were initially discordant for diabetes were islet autoantibody–positive before diabetes developed). Eighty-three monozygotic twins without diabetes were prospectively followed for antibody expression (i.e., GAD65, ICA512, insulin, and cytoplasmic islet-cell antibodies),5 progression to diabetes, or both for up to 43.8 years (mean, 12.8; median, 8.5; range, 0 to 43.8). Twins were identified at the Joslin Diabetes Center and the Barbara Davis Center for Childhood Diabetes and through the Diabetes Prevention Trial–Type 1 Diabetes.

As shown in Figure 1Figure 1Progressive Development of Anti-Islet Autoimmunity and Diabetes., by 60 years of age, the cumulative incidence of diabetes among monozygotic twins who were initially discordant for diabetes was 65% (95% confidence interval [CI], 39 to 91), and persistent autoantibody positivity, type 1 diabetes, or both had developed in 78% (95% CI, 61 to 95). Among 32 autoantibody-positive monozygotic twins, the risk of diabetes was 89% (95% CI, 72 to 100) within 16 years after the first positive antibody test. Because we studied only monozygotic twins who were initially discordant for diabetes, and a subgroup of twins before 1992 was not assessed with more recently available biochemical autoantibody assays (GAD65 and ICA512), the rates of progression to autoantibody positivity shown in the figure are probably underestimates.5

We conclude that with prospective long-term follow-up, both autoantibody positivity and diabetes frequently develop in monozygotic twins of patients with type 1 diabetes, even if the twins were initially discordant for diabetes. We believe that, at least in studies of autoimmune disorders, estimates of the concordance rate for diabetes among monozygotic twins should include long-term follow-up.

Maria J. Redondo, M.D., Ph.D.
Joy Jeffrey, B.S.
Pamela R. Fain, Ph.D.
George S. Eisenbarth, M.D., Ph.D.
Barbara Davis Center for Childhood Diabetes, Aurora, CO 80045
george.eisenbarth@uchsc.edu

Tihamer Orban, M.D.
Joslin Diabetes Center, Boston, MA 02215

Supported by grants from the Juvenile Diabetes Foundation (11-2002-696, to Dr. Redondo), the National Institutes of Health (DK32083), the Autoimmunity Prevention Center (AI50964), and the American Diabetes Association (1-04-RA-23, to Dr. Fain).

Dr. Eisenbarth reports receiving royalties from Kronus and Quest Laboratories.

No other potential conflict of interest relevant to this letter was reported.

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