Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Pediatr Diabetes. 2020 Nov;21(7):1202-1209. doi: 10.1111/pedi.13085. Epub 2020 Aug 9.
Our aim was to elucidate the role of diet in type 1 diabetes (T1D) by examining combinations of nutrient intake in the progression from islet autoimmunity (IA) to T1D.
We measured 2457 metabolites and dietary intake at the time of seroconversion in 132 IA-positive children in the prospective Diabetes Autoimmunity Study in the Young. IA was defined as the first of two consecutive visits positive for at least one autoantibody (insulin, GAD, IA-2, or ZnT8). By December 2018, 40 children progressed to T1D. Intakes of 38 nutrients were estimated from semiquantitative food frequency questionnaires. We tested the association of each metabolite with progression to T1D using multivariable Cox regression. Nutrient patterns that best explained variation in candidate metabolites were identified using reduced rank regression (RRR), and their association with progression to T1D was tested using Cox regression adjusting for age at seroconversion and high-risk HLA genotype.
In stepwise selection, 22 nutrients significantly predicted at least two of the 13 most significant metabolites associated with progression to T1D, and were included in RRR. A nutrient pattern corresponding to intake lower in linoleic acid, niacin, and riboflavin, and higher in total sugars, explained 18% of metabolite variability. Children scoring higher on this metabolite-related nutrient pattern at seroconversion had increased risk for progressing to T1D (HR = 3.17, 95%CI = 1.42-7.05).
Combinations of nutrient intake reflecting candidate metabolites are associated with increased risk of T1D, and may help focus dietary prevention efforts.
通过研究从胰岛自身免疫（IA）到 1 型糖尿病（T1D）进展过程中营养素摄入的组合，阐明饮食在 T1D 中的作用。
我们在前瞻性糖尿病自身免疫研究中的 132 名 IA 阳性儿童发生血清转化时测量了 2457 种代谢物和饮食摄入量。IA 定义为连续两次至少有一项自身抗体（胰岛素、GAD、IA-2 或 ZnT8）阳性的首次就诊。截至 2018 年 12 月，有 40 名儿童进展为 T1D。通过半定量食物频率问卷估计了 38 种营养素的摄入量。我们使用多变量 Cox 回归测试了每种代谢物与进展为 T1D 的相关性。使用降秩回归（RRR）识别了最佳解释候选代谢物变异的营养素模式，并使用 Cox 回归调整血清转化时的年龄和高危 HLA 基因型来测试其与进展为 T1D 的相关性。
在逐步选择中，有 22 种营养素显著预测了与进展为 T1D 相关的 13 种最重要代谢物中的至少两种，并且被包括在 RRR 中。与 linoleic 酸、烟酸和核黄素摄入较低，总糖摄入较高相对应的营养素模式解释了 18%的代谢物变异性。在血清转化时具有较高代谢物相关营养素模式评分的儿童进展为 T1D 的风险增加（HR=3.17，95%CI=1.42-7.05）。
反映候选代谢物的营养素组合与 T1D 风险增加相关，可能有助于集中进行饮食预防工作。
