Risk of Islet and Celiac Autoimmunity in Cotwins of Probands with Type 1 Diabetes

Abstract

Concordance for persistent islet autoimmunity (IA) and type 1 diabetes (T1D) in monozygotic twins (MZ) after one twin is diagnosed has been highly variable (30-70%), while risk for development of IA in dizygotic twins (DZ) is thought to be similar to non-twin siblings. Since 1995, the Twin Family Study at the Barbara Davis Center has followed 336 twins (168 twin probands diagnosed with T1D and 168 cotwins) with a median follow-up of 14 years (ICR:10-18 years). Zygosity testing confirmed a total of 80 MZ pairs and 88 DZ pairs. Cotwins were followed for the development of IA and celiac autoimmunity (CDA). In MZ cotwins, cumulative incidence for IA was 14% by age 20 and 63% by age 45, while development of CDA was 10% by 20 years. Development of IA and CDA by age 20 was 9.2% and 12.3% in DZ cotwins respectively, with development of IA reaching 70% by age 30 (Figure). In Cox proportional hazards models, only the proband’s age at diagnosis, but not sex, HLA-DR3 nor DR4 were associated with time to IA and CDA in cotwins. In MZ twins, younger age of the proband was associated with an increased hazard ratio (HR) for both IA and CDA, while younger age in DZ twins was associated with an increased HR for IA only. In conclusion, CDA risk does not appear to increase after age 15. With long term follow-up, cumulative incidence for IA is high in DZ twins, similar to MZ twins, suggesting a role of possible early environmental factors shared by T1D-discordant cotwins. Disclosure T.M. Triolo: None. A.R. Fouts: None. L. Pyle: None. L. Yu: None. P. Gottlieb: Advisory Panel; Self; Bristol-Myers Squibb Company. Research Support; Self; Caladrius Biosciences, Inc.. Advisory Panel; Self; Eli Lilly and Company. Board Member; Self; ImmunoMolecular Therapeutics. Consultant; Self; Kamada. Research Support; Self; JDRF, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk Inc., MacroGenics, Inc., Pfizer Inc.. Advisory Panel; Self; Viacyte, Inc.. Research Support; Self; GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc.. A. Steck: None.