AIMS/HYPOTHESIS We studied the association of plasma ascorbic acid with the risk of developing islet autoimmunity and type 1 diabetes and examined whether SNPs in vitamin C transport genes modify these associations. Furthermore, we aimed to determine whether the SNPs themselves are associated with the risk of islet autoimmunity or type 1 diabetes. METHODS We used a risk set sampled nested case-control design within an ongoing international multicentre observational study: The Environmental Determinants of Diabetes in the Young (TEDDY). The TEDDY study followed children with increased genetic risk from birth to endpoints of islet autoantibodies (350 cases, 974 controls) and type 1 diabetes (102 cases, 282 controls) in six clinical centres. Control participants were matched for family history of type 1 diabetes, clinical centre and sex. Plasma ascorbic acid concentration was measured at ages 6 and 12 months and then annually up to age 6 years. SNPs in vitamin C transport genes were genotyped using the ImmunoChip custom microarray. Comparisons were adjusted for HLA genotypes and for background population stratification. RESULTS Childhood plasma ascorbic acid (mean ± SD 10.76 ± 3.54 mg/l in controls) was inversely associated with islet autoimmunity risk (adjusted OR 0.96 [95% CI 0.92, 0.99] per +1 mg/l), particularly islet autoimmunity, starting with insulin autoantibodies (OR 0.94 [95% CI 0.88, 0.99]), but not with type 1 diabetes risk (OR 0.93 [95% Cl 0.86, 1.02]). The SLC2A2 rs5400 SNP was associated with increased risk of type 1 diabetes (OR 1.77 [95% CI 1.12, 2.80]), independent of plasma ascorbic acid (OR 0.92 [95% CI 0.84, 1.00]). CONCLUSIONS/INTERPRETATION Higher plasma ascorbic acid levels may protect against islet autoimmunity in children genetically at risk for type 1 diabetes. Further studies are warranted to confirm these findings. DATA AVAILABILITY The datasets generated and analysed during the current study will be made available in the NIDDK Central Repository at https://www.niddkrepository.org/studies/teddy.

中文翻译：

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血浆抗坏血酸与胰岛自身免疫性疾病和1型糖尿病的风险：TEDDY研究。

目的/假设我们研究了血浆抗坏血酸与发生胰岛自身免疫性疾病和1型糖尿病的风险之间的关系，并研究了维生素C转运基因中的SNP是否修饰了这些关系。此外，我们旨在确定SNP本身是否与胰岛自身免疫或1型糖尿病风险相关。方法我们在一项正在进行的国际多中心观察性研究中使用了风险集抽样的嵌套病例对照设计：年轻人中糖尿病的环境决定因素（TEDDY）。TEDDY研究追踪了六个临床中心从出生到胰岛自身抗体（350例，974例对照）和1型糖尿病（102例，282例对照）的遗传风险增加的儿童。将对照参与者的1型糖尿病家族病史，临床中心和性别进行匹配。在6和12个月大时测量血浆抗坏血酸浓度，然后每年测量一次，直到6岁。使用ImmunoChip定制微阵列对维生素C转运基因中的SNP进行基因分型。比较针对HLA基因型和背景人群分层进行了比较。结果儿童血浆抗坏血酸（对照组中的平均值±SD 10.76±3.54 mg / l）与胰岛自身免疫风险呈负相关（校正后为每+1 mg / l OR 0.96 [95％CI 0.92，0.99]或胰岛自身免疫）胰岛素自身抗体（OR 0.94 [95％CI 0.88，0.99]），但没有1型糖尿病风险（OR 0.93 [95％Cl 0.86，1.02]）。SLC2A2 rs5400 SNP与1型糖尿病风险增加相关（OR 1.77 [95％CI 1.12，2.80]），与血浆抗坏血酸无关（OR 0.92 [95％CI 0.84，1.00]）。结论/解释较高的血浆抗坏血酸水平可以预防遗传上有1型糖尿病风险的儿童的胰岛自身免疫。有必要做进一步的研究来证实这些发现。数据可用性当前研究过程中生成和分析的数据集将在NIDDK中央存储库中提供，网址为https://www.niddkrepository.org/studies/teddy。