People with type 1 diabetes (T1D) are at increased risk for comorbid autoimmune disease (CAID). The TrialNet Pathway to Prevention (PTP) Study screens relatives of people with T1D for islet autoantibodies (Ab) to determine T1D risk. PTP Ab+ participants self-reported (Y vs. N) whether or not they had CAIDs at the start of monitoring. Outside of celiac disease, CAID has not been examined in Ab+ participants. Of the 5,740 Ab+ participants, 586 (10.2%; 95% CI: 9.4 - 11.0%) reported having a CAID. Of those with a single confirmed Ab+, GADA+ participants had a higher prevalence of CAID (230/1709=13.5%) vs. those who were IA-2A+ (8/88=9.1%) or mIAA+ (40/592=6.8%; p<0.0001). Across all Ab+ participants, the number of Abs was inversely associated with prevalence of CAID at baseline, where a higher number of Abs corresponded to a lower likelihood of CAID (1 Ab+: 278/2393=11.6%; 2 Ab+: 165/1388=11.9%; 3 Ab+: 73/891=8.2%; 4 Ab+: 44/687=6.4%; 5 Ab+: 26/381=6.8%; p<0.0001). The most prevalent CAID reported was thyroid disease (5.7%) with celiac disease reported in 1.3%. The influence of HLA status on CAID prevalence was mixed; celiac disease was more prevalent in those with DR3 (OR=2.79, p<0.0001) while thyroid disease was less prevalent in those with DR4/DQ8 (OR=0.61, p<0.0001). Although being single confirmed Ab+ at screening was associated with a higher likelihood of having CAID in the univariate setting, it was significantly protective (OR=0.77; p=0.007) when adjusting for age, sex and HLA status. In multivariable logistic regression models, the prevalence of CAID at baseline was associated with older age, being female and HLA DR4/DQ8 negative.

In conclusion, the reported prevalence rates of CAID is high in Ab+ relatives of people with T1D, inversely correlated with the number of Ab present, and related to DR3 and DR4/DQ8 haplotypes. The change in the direction of association of CAID with Ab number after an adjustment for HLA status suggests that DR3 and DR4/DQ8 could contribute to both CAID and Ab development.


K. Simmons: None. S. Geyer: None. D.K. Wherrett: None. H.M. Ismail: None. M. Lundgren: None. L.E. Bocchino: None. J.M. Sosenko: None. C. Greenbaum: Research Support; Self; Janssen Research & Development. A. Steck: None.


National Institute of Diabetes and Digestive and Kidney Diseases (5U01DK0855095, K12DK094712-08)

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at