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

描述（由申请人提供）：我们正在进行一项正在进行的研究，比较10周的果糖或葡萄糖消耗量（能量需求的25%）对老年人（40岁以上），超重/肥胖（BMI：25-35 kg/m2）成人的脂质参数和胰岛素抵抗和炎症指数的影响。本研究的当前结果提供了证据，表明果糖的消耗促进了2周内致动脉粥样硬化脂质谱和葡萄糖耐受不良/胰岛素抵抗的发展，而葡萄糖的消耗则没有。因此，高果糖饮食可能会导致代谢综合征和心血管疾病的发展。我们建议通过追求以下具体目标来扩展我们的研究：1：确定在年轻、正常体重和超重/肥胖成人（18-40岁）中产生脂质失调和胰岛素抵抗所需的膳食果糖量。我们建议进行一项剂量反应研究，受试者在2周内自由选择饮食，补充10%、17.5%或25%的能量需求作为果糖甜味饮料。第二章：比较食用两周自选的自由饮食的影响，这些饮食含有10%，17.5%或25%的能量需求作为高果糖玉米糖浆（HFCS）加糖饮料与果糖在正常体重和超重/肥胖成人（18-40岁）中引起的影响。我们有初步的数据表明，尽管含有比纯果糖少45%的果糖，但以25%的能量需求消费HFCs甜味饮料，会增加餐后甘油三酯，其程度与消耗25%的能量作为纯果糖相同。因此，我们假设HFCS将促进比单独果糖更易致动脉粥样硬化的脂质谱的发展。3：检验果糖和HFCS将导致异位肝甘油三酯蓄积和胰岛素抵抗的可比增加的假设。我们认为果糖摄入引起的胰岛素抵抗的诱导是通过一种机制介导的，该机制涉及果糖诱导的脂质失调和肝脏异位脂质沉积增加，而不是涉及肝脏果糖代谢更直接影响的机制。该研究被设计为前瞻性、盲法饮食干预研究，有3天的复合碳水化合物饮食基线期和2周的饮食干预期，在此期间，参与者在进餐时饮用果糖或HFCs加糖饮料（提供10%、17.5%或25%的能量）。在干预期间，受试者住在家里，并提供果糖或HFCs增甜的饮料，这些饮料与自选的随意（通常）饮食一起沿着消耗。包括4小时口服葡萄糖耐量和氘代葡萄糖处置试验、通过MRI测量肝脏甘油三酯蓄积和24小时血液收集的程序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分校临床与转化科学中心临床研究中心进行。项目叙述：我们实验室最近的结果表明，在每餐中以25%的热量需求饮用果糖甜味饮料2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的风险增加有关，由于1977年至2001年期间，含果糖的含糖饮料的消费量增加了一倍以上，这些发现具有重要的公共卫生意义。需要进行拟议的研究，以确定饮用含果糖和高果糖玉米糖浆的甜味饮料对年轻，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，以便建立糖消费的安全水平。

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.