Effects of 2wk fructose & HFCS consumption on lipid dysregulation & insulin resis

描述(申请人提供)：我们正在进行一项正在进行的研究，比较老年人(+40岁)、超重/肥胖(BMI：25-35公斤/平方米)成年人10周果糖或葡萄糖摄入量(能量需要量的25%)对血脂参数和胰岛素抵抗和炎症指数的影响。这项研究目前的结果提供了证据，证明摄入果糖会在两周内促进致动脉粥样硬化的脂代谢和葡萄糖耐受/胰岛素抵抗的发展，而葡萄糖的摄入则不会。因此，高果糖饮食很可能会导致代谢综合征和心血管疾病的发生。我们建议通过追求以下具体目标来扩大我们的调查范围：1：确定年轻、正常体重和超重/肥胖成年人(18-40岁)产生脂代谢紊乱和胰岛素抵抗所需的膳食果糖含量。我们建议进行一项剂量-反应研究，受试者在两周内食用自己选择的随意饮食，并补充10%、17.5%或25%的能量需求作为果糖含糖饮料。2：在正常体重和超重/肥胖成年人(18-40岁)中，比较两周自行选择的包含10%、17.5%或25%能量需要量的随意饮食(如高果糖玉米糖浆含糖饮料)与果糖引起的影响。我们有初步数据表明，尽管果糖含量比纯果糖少45%，但摄入能量需求的25%的HFCS含糖饮料会增加餐后甘油三酯，其程度与消耗纯果糖的25%相同。因此，我们假设，与单独使用果糖相比，HFCS将促进致动脉粥样硬化脂谱的形成。3：检验果糖和HFCS将导致异位肝脏甘油三酯蓄积和胰岛素抵抗相应增加的假设。我们认为，摄入果糖导致的胰岛素抵抗是通过果糖诱导的脂质失调和肝脏中异位脂肪沉积增加的机制来调节的，而不是通过更直接地影响肝脏果糖代谢的机制来介导的。这项研究是一项前瞻性、盲目的饮食干预研究，复杂碳水化合物饮食的基线时间为3天，饮食干预阶段为2周，在此期间，参与者在进餐时饮用果糖或HFCS甜味饮料(提供10%、17.5%或25%的能量)。在干预期间，受试者住在家里，并得到果糖或HFCS甜味饮料，这些饮料与自己选择的随意(通常)饮食一起饮用。在基线期间和干预第1周和第2周结束时，在加州大学戴维斯临床与翻译科学中心临床研究中心进行了包括4小时口服葡萄糖耐量和氚葡萄糖处置试验、MRI测量肝脏甘油三酯蓄积和24小时血液采集在内的各项检查。项目简介：我们实验室的最新结果表明，在每餐中饮用含有25%卡路里需要量的果糖饮料，持续两周会导致血液中胆固醇和甘油三酯水平升高，并增加40岁以上超重和肥胖男性和女性的胰岛素抵抗。这些变化与心脏病和糖尿病风险的增加有关，而且由于含果糖的含糖饮料的消费量在1977至2001年间增加了一倍多，这些发现对公众健康具有重要影响。拟议的研究需要确定饮用加果糖和高果糖玉米糖浆的饮料对年轻、正常体重和超重成年人的影响，并确定产生这些不良影响所需的果糖摄入量，以便建立安全的糖分摄入量。

DESCRIPTION (provided by applicant): We are conducting an ongoing study comparing the effects of 10 weeks of fructose or glucose consumption at 25 percent of energy requirements on lipid parameters and indices of insulin resistance and inflammation in older (+40 years), overweight/obese (BMI: 25-35 kg/m2) adults. Current results from this study provide evidence that consumption of fructose promotes the development of an atherogenic lipid profile and glucose intolerance/insulin resistance within 2 weeks, while glucose consumption does not. Thus, it is likely that diets high in fructose could contribute to the development of metabolic syndrome and cardiovascular disease. We propose to expand our investigation by pursuing the following Specific Aims: 1: Determine the amount of dietary fructose required to produce lipid dysregulation and insulin resistance in younger, normal weight and overweight/obese adults (18-40 years). We propose to conduct a dose-response study in which subjects consume self-selected, ad libitum diets for 2 weeks supplemented with 10, 17.5 or 25 percent of energy requirements as fructose-sweetened beverages. 2: Compare the effects of consuming two weeks self-selected ad libitum diets containing 10, 17.5 or 25 percent of energy requirements as high fructose corn syrup (HFCS)-sweetened beverages to the effects induced by fructose in normal weight and overweight/obese adults (18-40 years). We have preliminary data demonstrating that consumption of HFCS-sweetened beverages at 25 percent of energy requirements, despite containing 45 percent less fructose than pure fructose, increases postprandial triglycerides to the same degree as consuming 25 percent energy as pure fructose. Therefore, we hypothesize that HFCS will promote the development of an atherogenic lipid profile comparably to fructose alone. 3: Test the hypothesis that fructose and HFCS will cause comparable increases in ectopic hepatic triglyceride accumulation and insulin resistance. We propose that induction of insulin resistance resulting from fructose consumption is mediated through a mechanism that involves fructose-induced lipid dysregulation and increased ectopic lipid deposition in the liver, rather than a mechanism involving more direct effects of hepatic fructose metabolism. The study is designed as a prospective, blinded diet intervention study, with a 3-day baseline period on a complex carbohydrate diet and a 2-week diet intervention phase, during which the participants consume either fructose- or HFCS-sweetened beverages (providing 10 percent, 17.5 percent or 25 percent of energy) with meal. During the intervention, the subjects reside at home and are provided with fructose- or HFCS-sweetened beverages that are consumed along with a self-selected ad libitum (usual) diet. Procedures, which include 4-hour oral glucose tolerance and deuterated glucose disposal tests, measurement of hepatic triglyceride accumulation by MRI, and 24-hour blood collections are performed during the baseline period and at the end of Intervention Weeks 1 and 2 at the UC Davis Clinical & Translational Science Center Clinical Research Center. Project Narrative: Recent results from our laboratory indicate that drinking beverages sweetened with fructose at 25 percent of caloric requirements at each meal for 2 weeks causes increased cholesterol and triglyceride levels in the blood and increased insulin resistance in overweight and obese men and women over 40 years old. These changes are associated with an increased risk for heart disease and diabetes, and since consumption of sugar-sweetened beverages containing fructose has more than doubled between 1977 and 2001, these findings have important public health implications. The proposed studies are needed to determine the effects of drinking beverages sweetened with fructose and high fructose corn syrup in younger, normal weight and overweight adults, and to determine the amount of fructose intake that is required to produce these undesirable effects so that safe levels of sugar consumption can be established.