Application of predictive biomarkers of sugars and animal protein intake for investigation of dietary measurement error and its effect on diet-disease associations

项目摘要 开发新的方法来获得准确的饮食摄入量估计是揭示真实情况的关键 饮食摄入量与疾病风险之间的关联，最终目的是建立基于证据的 指导方针。虽然有证据表明饮食中的糖分会增加患龋齿和肥胖的风险 糖与心血管疾病(CVD)和2型糖尿病风险增加之间的关联更强 (T2D)，癌症仍然没有定论。总蛋白和动物蛋白摄入量与T2D关系的研究结果 风险和心血管疾病或全因死亡率也是不一致的。饮食中的生物标记物缓解了 与营养学中常用的自我报告膳食仪器相关的测量误差(ME) 流行病学，并已被用于验证和校准自我报告的饮食或调整自我报告的ME 报告，并揭示重要的关联。在此续订申请的父项目中，(SugarsBio Study， U01-CA197902)，我们确认24小时尿蔗糖和果糖(24uSF)是总的预测生物标志物。 糖(TS)的摄入量，并证明了用于估计生物标志物的生物标志物方程的可携带性。 基于不同人群的TS摄入量和使用情况。此外，我们已经确定了血清中的碳 同位素比(CIR)作为预测AP/总蛋白摄入量比(APR)的候选生物标志物 蛋白质质量的生物标记物，并建立了可用于产生生物标记物的生物标记物方程。 在现有生物样本的研究中基于APR。这项建议的目的是调查公用事业 在两个前瞻性队列的不同人群中应用24uSF和血清CIR生物标志物。 为此，我们将利用来自两个大型饮食验证研究的数据进行全面验证 嵌套在队列中的协议(IDATA和SOLNAS)、NIH-AARP饮食与健康(AARP)研究和 西班牙裔社区健康研究/拉丁裔研究(HCHS/SOL)。首先，我们将研究自我报告中的自我评价 TS、APR、AP和植物蛋白(PP)摄入量，使用24uSF和血清CIR生物标志物。第二，我们将 根据IDATA和SOLNAS中的生物标志物，建立自我报告摄入量的回归校正方程 我们将在他们各自的群体中应用。第三，我们将调查未校准和已校准(即ME- 更正)自我报告的TS、AP、PP和APR摄入量与AARP中CVD死亡率和T2D风险的关系 在HCHS/SOL队列中。我们的研究将是第一个应用新发展的美国人口的研究- 基于糖和蛋白质摄取的生物标志物及其校准方程与种族/民族多样性的美国 以人群为基础的研究和评估ME校正的饮食摄入量与慢性病的关系。通过 告知在未来的饮食验证研究中应用这些生物标记物的最佳实践 饮食-疾病协会，这项建议将大大有助于改善饮食评估和 加强营养流行病学研究的科学严谨性。

Project Summary Developing new approaches for obtaining accurate estimates of dietary intake is crucial for revealing true associations between dietary intakes and disease risk, with the ultimate aim of establishing evidence-based guidelines. While the evidence on dietary sugars and increased risks of dental caries and obesity have been stronger, the association between sugars and increased risk of cardiovascular disease (CVD), type 2 diabetes (T2D), and cancer remains inconclusive. The findings on total and animal protein (AP) intake in relation to T2D risk and CVD or all-cause mortality have also been inconsistent. Dietary biomarkers alleviate the problem of measurement errors (ME) associated with self-reporting dietary instruments commonly used in nutritional epidemiology, and have been used to validate and calibrate self-reported diet or to adjust for ME in self- reports, and reveal important associations. In the parent project of this renewal application, (SugarsBio study, U01-CA197902), we confirmed 24-h urinary sucrose and fructose (24uSF) as a predictive biomarker of total sugars (TS) intake, and demonstrated the transportability of the biomarker equation for estimating biomarker- based TS intake and its use across different populations. Furthermore, we have identified serum carbon isotope ratio (CIR) as a candidate predictive biomarker of the AP to total protein intake ratio (APR), a novel biomarker of protein quality, and developed a biomarker equation that can be used to generate biomarker- based APR in studies with available biological samples. The aim of this proposal is to investigate the utility and application of 24uSF and serum CIR biomarkers in diverse populations in two prospective cohorts. For this purpose, we will leverage data from two large dietary validation studies with comprehensive validation protocols (IDATA and SOLNAS) nested within cohorts, the NIH-AARP Diet and Health (AARP) Study and the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). First, we will study the ME in self-reported TS, and APR, AP and plant protein (PP) intake, using 24uSF and serum CIR biomarkers. Second, we will develop regression calibration equations for self-reported intake, based on biomarkers, in IDATA and SOLNAS that we will apply in their respective cohorts. Third, we will investigate uncalibrated and calibrated (i.e., ME- corrected) self-reported intakes of TS, AP, PP and APR in relation to CVD mortality in the AARP, and T2D risk in the HCHS/SOL cohort. Our study will be the first study that applies the newly developed US population- based sugars and protein intake biomarkers and their calibration equations to race/ethnically diverse US population-based studies and evaluates ME-corrected dietary intakes in relation to chronic diseases. By informing the best practices for applying these biomarkers in future diet validation studies and studies of diet-disease associations, this proposal will significantly contribute to improving dietary assessments and enhancing scientific rigor of nutritional epidemiologic studies.