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估计饮食摄入量是至关重要的揭示真正的 饮食摄入量与疾病风险之间的关系，最终目的是建立基于证据的 指南虽然关于饮食中的糖和龋齿和肥胖风险增加的证据已经被证实， 糖与心血管疾病（CVD）、2型糖尿病（DM）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（AP）摄入量与T2 D相关的研究结果 风险和CVD或全因死亡率也不一致。饮食生物标志物缓解了 与营养学中常用的自我报告饮食工具相关的测量误差（ME） 流行病学，并已被用于验证和校准自我报告的饮食或自我调整ME。 报告，并揭示重要的协会。在本次更新申请的父项目中，（SugarsBio研究， U 01-CA 197902），我们证实24小时尿蔗糖和果糖（24 uSF）作为总 糖（TS）摄入量，并证明了生物标志物方程的可移植性，用于估计生物标志物- 基于TS摄入量及其在不同人群中的使用。此外，我们还鉴定了血清碳 同位素比（CIR）作为AP与总蛋白摄入比（APR）的候选预测生物标志物， 蛋白质质量的生物标志物，并开发了一个生物标志物方程，可用于生成生物标志物- 基于可用生物样本的APR研究。本建议的目的是调查的效用 以及24 uSF和血清CIR生物标志物在两个前瞻性队列的不同人群中的应用。 为此，我们将利用两项大型饮食验证研究的数据进行全面验证 方案（IDATA和SOLNAS）嵌套在队列中，NIH-AARP饮食和健康（AARP）研究和 西班牙裔社区健康研究（HCHS/SOL）。首先，我们将研究自我报告中的ME TS和APR、AP和植物蛋白（PP）摄入量，使用24 uSF和血清CIR生物标志物。二是 基于IDATA和SOLNAS中的生物标志物，开发自我报告摄入量的回归校准方程 我们将在他们各自的队列中应用。第三，我们将调查未校准和校准（即，我- AARP中自我报告的TS、AP、PP和APR摄入量与CVD死亡率和T2 D风险的关系 在HCHS/SOL队列中。我们的研究将是第一个应用新开发的美国人口的研究- 基于糖和蛋白质摄入量的生物标志物及其校准方程，以种族/种族多样化的美国 基于人口的研究和评估与慢性病相关的ME校正饮食摄入量。通过 为在未来的饮食验证研究和以下研究中应用这些生物标志物提供最佳实践 饮食疾病协会，这项建议将大大有助于改善饮食评估， 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.