Increased Incidence of Pediatric Type 1 Diabetes With Novel Association With Coxsackievirus A Species in Young Children but Declined Incidence in Adolescents in Taiwan

OBJECTIVE Type 1 diabetes (T1D) has been linked to enterovirus infection in small population-based epidemiological studies. We investigated the secular relationship of T1D incidence with enterovirus infection and enterovirus species using nationwide population-based analysis. RESEARCH DESIGN AND METHODS We accessed the National Health Insurance Research Database of Taiwan to identify T1D and enterovirus infection cases from 2001 to 2015. Enterovirus serotype isolation rates were obtained from the nationwide laboratory surveillance systems. Negative binomial regression models assessed the incidence trend, and extended Cox proportional hazards models analyzed the association of enterovirus infection with T1D incidence. Spearman correlation coefficients evaluated the correlation between T1D incidence and circulating enterovirus species. RESULTS T1D incidence rates in youth younger than 20 years were 6.30 and 5.02 per 100,000 person-years in 2001 and 2015 (P = 0.287), respectively. T1D incidence increased significantly in children aged 0–6 years (P < 0.001) but decreased in adolescents aged 13–19 years (P = 0.011). The T1D risk in children aged 0–6 years with enterovirus infection was significantly higher than that in noninfected subjects (hazard ratio 1.46; 95% CI 1.35–1.58; P < 0.001). Additionally, TID incidence in children aged 0–6 years was significantly correlated with the isolation rates of coxsackievirus A species (r = 0.60; P = 0.017), but no association was found beyond the age of 7. CONCLUSIONS We demonstrated that T1D incidence increased in children aged 0–6 years but decreased in adolescents aged 13–19 years in Taiwan. Enterovirus-infected subjects younger than 7 years had a higher risk of T1D than noninfected subjects.