DIETS FOR DYSLIPIDEMIA IN THE METABOLIC SYNDROME

代谢综合征血脂异常的饮食

• 批准号: 7257033
• 负责人: ROBERT Henry KNOPP
• 金额: $ 75.21万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-15 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7257033
• 关键词: Apolipoproteins B; Apoprotein (B); Blood Vessels; Body Weight; Body Weight decreased; Carbohydrates; Cholesterol; Condition; Consensus; Coronary heart disease; Counseling; Crossover Design; Diet; Dietary Fats; Drops; Dyslipidemias; Elements; Elevation; Eligibility Determination; Endothelium; Epidemic; Exercise; Fasting; Fat-Restricted Diet; Fatty acid glycerol esters; Food; Glucose; High Density Lipoproteins; Hypertriglyceridemia; Inflammation; Inflammatory; Insulin; Intake; Life; Lipids; Lipoproteins; Low-Density Lipoproteins; Measures; Mediating; Metabolic; Metabolic syndrome; Nutritionist; Obesity; Observational Study; Persons; Physiological; Plant Roots; Plasma; Proteins; Randomized; Rate; Recommendation; Research; Research Design; Research Personnel; Solutions; Standards of Weights and Measures; Stress; Testing; Triglycerides; Tumor Necrosis Factor-alpha; Universities; Vascular Cell Adhesion Molecule-1; Washington; Week; Weight; Woman; adiponectin; base; brachial artery; carbohydrate metabolism; cardiovascular risk factor; cysteine rich protein; cytokine; design; feeding; human TNF protein; hypercholesterolemia; improved; indexing; intercellular cell adhesion molecule; men; programs; response; saturated fat; vascular inflammation

DESCRIPTION (provided by applicant): The metabolic syndrome (MetS) is comprised of a constellation of cardiovascular risk factors rooted in the current epidemic of obesity. Two of the defining features of MetS are high triglycerides and low HDL, i.e. the dyslipidemia of MetS. Standard hygienic recommendations for this dyslipidemia are weight loss and exercise, but at weight stability, there is no consensus on the dietary fat and carbohydrate proportions best suited for the dyslipidemia or the associated impaired vascular reactivity of MetS. Diets higher in fat, lower in carbohydrate may be more beneficial in MetS. Weight-loss studies show that higher fat, lower carbohydrate intakes are associated with lower triglyceride levels in obese persons, but lipoprotein, inflammatory and vascular responses to dietary perturbation in weight stability (the usual physiological state) have not been studied prospectively. Standard low fat, high carbohydrate diets in dyslipidemic persons yield 1/3rd of the LDL lowering of persons with simple hypercholesterolemia. Such persons are also less sensitive to higher saturated fat feeding. Consistent with these findings are lower rates of coronary disease in persons ingesting higher fat diets in observational studies. These observations plus physiological reasoning suggest the following hypothesis: Higher fat intake is more beneficial than conventional fat restricted diet in MetS for; 1) managing dyslipidemia, 2) reducing inflammatory stress and 3) correcting endothelium-mediated vascular reactivity, an immediate index of atherosclerotic stress. The study will compare the lipoprotein and vascular effects of two diets distinct in fat and carbohydrate content in a randomized, 4-week, crossover, feeding study design, using food prepared in the metabolic kitchen of the University of Washington GCRC. Diets will contain 40en% fat. 45en% carbohydrate or 20en% fat. 65en% carbohydrate with equivalent protein (15en%) and saturated fat (8en%). Weight will remain stable. Eligibility criteria are triglyceride >150mg/dl and any two other criteria of MetS. Seventy-two men and women will be randomized to yield 60 finished subjects at a 20% drop out rate. Weight and other vital signs will be measured twice weekly when food is picked-up from the GCRC. Lipoprotein lipids will be measured at 0, 3 and 4 weeks. Apoproteins B and A-l, LDL buoyancy, glucose, insulin, adiponectin, inflammatory cytokines and flow-mediated brachial artery reactivity will be measured at 0 and 4 weeks. A 4-month extension will continue the second diet assignment under dietician counseling with repeat testing. Expected results: 40en% fat diet in MetS subjects will yield improvements in non-HDL-C, other lipoprotein and glycemic variables, inflammation and brachial reactivity compared to 20en% fat. This study will be the first to demonstrate dietary benefit for dyslipidemia, inflammation and vascular stress in MetS at stable weight.

描述（由申请人提供）：代谢综合征（MetS）由一系列源于当前肥胖流行的心血管危险因素组成。 MetS 的两个定义特征是高甘油三酯和低 HDL，即 MetS 的血脂异常。对于这种血脂异常的标准卫生建议是减肥和锻炼，但在体重稳定的情况下，对于最适合血脂异常或相关的 MetS 血管反应性受损的膳食脂肪和碳水化合物比例尚未达成共识。高脂肪、低碳水化合物的饮食可能对代谢综合征更有益。减肥研究表明，肥胖者较高的脂肪、较低的碳水化合物摄入量与较低的甘油三酯水平有关，但脂蛋白、炎症和血管对体重稳定性（通常的生理状态）饮食扰动的反应尚未进行前瞻性研究。血脂异常患者的标准低脂肪、高碳水化合物饮食降低的 LDL 效果是单纯性高胆固醇血症患者的 1/3。这些人对高饱和脂肪喂养也不太敏感。与这些发现一致的是，观察性研究中摄入高脂肪饮食的人患冠心病的几率较低。这些观察结果加上生理推理表明以下假设：在 MetS 中，较高的脂肪摄入量比传统的脂肪限制饮食更有益； 1) 控制血脂异常，2) 减少炎症应激，3) 纠正内皮介导的血管反应性，这是动脉粥样硬化应激的直接指标。该研究将在随机、为期 4 周的交叉喂养研究设计中，使用华盛顿大学 GCRC 代谢厨房准备的食物，比较两种脂肪和碳水化合物含量不同的饮食对脂蛋白和血管的影响。饮食中将含有 40en% 的脂肪。 45en% 碳水化合物或 20en% 脂肪。 65en% 碳水化合物以及同等蛋白质 (15en%) 和饱和脂肪 (8en%)。体重将保持稳定。资格标准是甘油三酯 >150mg/dl 以及 MetS 的任何其他两个标准。 72 名男性和女性将被随机抽取 60 名完成受试者，退出率为 20%。当从 GCRC 领取食物时，每周两次测量体重和其他生命体征。将在第 0、3 和 4 周时测量脂蛋白脂质。将在第0周和第4周时测量脱辅基蛋白B和A-1、LDL浮力、葡萄糖、胰岛素、脂联素、炎性细胞因子和血流介导的肱动脉反应性。延长 4 个月后，将在营养师咨询下继续进行第二次饮食分配并进行重复测试。预期结果：与 20en% 脂肪相比，MetS 受试者的 40en% 脂肪饮食将改善非 HDL-C、其他脂蛋白和血糖变量、炎症和肱动脉反应性。这项研究将首次证明体重稳定时膳食对 MetS 患者血脂异常、炎症和血管应激的益处。