Investigation of Biomarkers for Sugars Intake - A Controlled Feeding Study

 描述(申请人提供)：除了已证实的糖与龋齿和肥胖的联系外，与心血管疾病、2型糖尿病和癌症的联系在很大程度上仍然没有定论。大多数人群研究依赖于自我报告的饮食测量，已知这与巨大的测量误差有关，这可能会掩盖糖和疾病风险之间的真实关系，并可能解释观察到的证据缺乏一致性。开发新的方法以获得更准确的摄入量估计，对于获得更可靠的糖和疾病风险估计至关重要。最近，在英国的两项喂养研究中，24小时尿蔗糖和果糖(24uSF)被开发为糖摄入量的生物标志物。然而，关于这个生物标记物在美国参与者身上和在美国饮食背景下的表现和有效性的证据缺乏。此外，USF测量在现场尿液中的实用性从未被调查过，可能会对流行病学研究产生重大影响。另一个很有前途的糖类生物标志物，红细胞碳稳定同位素比率(D13C)是最近在阿拉斯加原住民中开发的。这种生物标记物仅针对自我报告进行了测试，从未在已知摄入量的喂养研究中进行过调查。我们现在建议进行一项15天的高度受控喂养研究，以全面调查24uSF和d13C作为糖摄入量生物标志物的单独和组合表现，并为这些有前景的生物标志物在美国参与者中的未来应用提供信息。这项研究将涉及107名年龄在18-70岁的男性和女性，他们在15-d的时间里只食用研究新陈代谢厨房提供的食物和饮料，这将模拟他们之前通过两个7-d食物记录评估的日常饮食。在15天的喂食期内，参与者将收集8个不连续的24小时尿液，并在基线、研究完成时和研究完成后5周收集血液样本。首先，我们将研究24uSF作为糖摄入量生物标志物的表现，我们将开发一个校准方程，该方程将定义24uSF作为美国参与者糖的无偏见测量的未来应用。此外，我们将调查在现货尿中测量USF作为摄入量的生物标记物的实用性；在两个24小时尿液收集日，参与者将在不同的容器中收集尿液。其次，我们将在受控的喂养研究条件下，调查红细胞d13C作为糖摄入量生物标志物在美国参与者中的表现。我们还将探索使用24小时尿d13C作为糖摄入量的衡量标准。第三，我们将研究以一种独特的方法结合24uSF和d13C的方法。结合这两个不相关的生物标志物，它们具有不同的误差来源和与摄入量的不同时间关系 可以提供一种更好的摄入量标准。这项研究将开发有效的糖类生物标记物，可用作美国个人糖类摄入量的无偏见测量，最终将使人们能够获得糖类疾病相关性的可靠风险估计。直到强大和强大 虽然发现了糖对健康不利影响的一致证据，但对普通公众来说，没有明确的指导意见。

 DESCRIPTION (provided by applicant): Apart from sugars' proven association with dental caries and obesity, the link to cardiovascular disease, type 2 diabetes and cancer remains largely inconclusive. Most population studies rely on self-reported measures of diet, known to be associated with large measurement error, which may be obscuring the true relationship between sugars and disease risk and may explain the lack of consistency in the observed evidence. Development of novel approaches for obtaining more accurate estimates of intake is crucial for attaining more reliable risk estimates for sugars and disease risk. Recently, 24-h urinary sucrose and fructose (24uSF) was developed as a biomarker of sugars intake in two UK-based feeding studies. However, evidence on the performance and the validity of this biomarker in U.S. participants and in the context of a U.S. diet is lacking. Further, the utility of uSF measure in spot urines has never been investigated and could have significant implications for epidemiologic studies. Another promising sugars biomarker, the carbon stable isotope ratio (d13C) in red blood cell (RBCs) has been recently developed among Alaska Natives. This biomarker has been tested against self-reports only, and has never been investigated in a feeding study with known intake. We now propose a 15-d highly-controlled feeding study to comprehensively investigate the performance of 24uSF and d13C as biomarkers of sugars intake, individually and in combination, and to inform future application of these promising biomarkers among U.S. participants. The study will involve 107 men and women aged 18-70 y, consuming only foods and beverages provided by the study metabolic kitchen for 15-d, that will mimic their usual diet, assessed previously by two 7-d food records. Over the 15-d feeding period, participants will collect 8 nonconsecutive 24-h urines, and blood samples will be collected at baseline, at study completion, and 5 weeks post-study completion. First we will investigate the performance of 24uSF as a biomarker of sugars intake and we will develop a calibration equation that will define the future application of 24uSF as an unbiased measure of sugars in U.S. participants. Further, we will investigate the utility of measuring uSF in spot urin as a biomarker of intake; on two 24-h urine collection days, participants will collect urine voids n separate containers. Second, we will investigate the performance of RBCs d13C as a biomarker of sugars intake among U.S. participants under controlled conditions of a feeding study. We will also explore the use of 24-h urinary d13C as a measure of sugars intake. Third, we will investigate approaches of combining 24uSF and d13C in a unique measure. Combining these two unrelated biomarkers with different sources of error and with different time-relation to intake may provide a superior measure of intake. This study will develop validated sugars biomarkers that can be used as unbiased measures of sugars intake among U.S. individuals that will ultimately allow obtaining reliable risk estimates of sugars-disease associations. Until strong and consistent evidence for adverse health effects of sugars is found, no firm guidance can be given to the general public.