Dietary vitamin C intake and the risk of islet autoimmunity and type 1 diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY) Study

Abstract Purpose We explored the associations between vitamin C intake and the risk of islet autoimmunity (IA) and/or type 1 diabetes in genetically at-risk children. Furthermore, we explored associations between vitamin C metabolism-related single nucleotide polymorphisms (SNPs) and type 1 diabetes outcomes. Methods The current study within Environmental Determinants of Diabetes in the Young (TEDDY) cohort included 8478 children followed up every 3–6 months for relevant autoantibodies and diet. Dietary vitamin C intake was assessed longitudinally throughout childhood using age-specific dietary assessment methods and analysed using repeated measurements. Cox regression was used for the primary analyses and Bayesian joint longitudinal-survival models as sensitivity analyses. Results A total of 777 (9.2%) children developed IA, including 292 (3.4%) with IAA-first and 337 (4.0%) with GADA-first autoimmunity; 319 (41.0%) progressed to type 1 diabetes. Mean (SD) vitamin C intake was 60.7 (38.8) mg/1000 kcal. Higher vitamin C intake was associated with an increased risk of IAA-first autoimmunity (adjusted hazard ratio 1.04; 95% confidence interval 1.00–1.07, per 10 mg/1000 kcal increase) while lowest and highest tertiles of intake were associated with increased risk of GADA-first autoimmunity as compared to mid-tertile [(1.65; 1.20–2.27) and (1.42; 1.02–1.98), respectively]. Sensitivity analyses using Bayesian joint longitudinal-survival models supported the primary findings and suggested nonlinear associations between vitamin C intake and the risks of IA and multiple IA. Associations between vitamin C-related SNPs and study outcomes did not withstand correction for multiple testing. Conclusion Vitamin C intake was not consistently associated with IA or progression to type 1 diabetes. However, the observed nonlinear association, with lowest risk for moderate intakes, merits further investigation. Trial registration NCT00279318, 06/09/2004.