DIETS FOR DYSLIPIDEMIA IN THE METABOLIC SYNDROME

描述(申请人提供)：代谢综合征(METS)是由一系列源于当前肥胖流行的心血管危险因素组成的。蛋氨酸的两个特征是高甘油三酯和低高密度脂蛋白，即蛋氨酸的血脂异常。治疗这种血脂异常的标准卫生建议是减肥和锻炼，但在体重稳定方面，对于最适合蛋氨酸代谢紊乱或相关血管反应性受损的饮食脂肪和碳水化合物比例，还没有达成共识。高脂肪、低碳水化合物的饮食可能对蛋氨酸更有益。减肥研究表明，肥胖者高脂肪、低碳水化合物摄入量与低甘油三酯水平相关，但在体重稳定(通常的生理状态)中，脂蛋白、炎症和血管对饮食扰动的反应还没有前瞻性的研究。标准低脂、高碳水化合物饮食对血脂异常人群的低密度脂蛋白降低率是单纯性高胆固醇血症患者的1/3。这类人对高饱和脂肪摄入也不太敏感。与这些发现一致的是，在观察性研究中，摄入高脂肪饮食的人患冠状动脉疾病的比率较低。这些观察和生理推理提出了以下假设：在蛋氨酸中，较高的脂肪摄入量比传统的脂肪限制饮食更有利于：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。这项研究将通过随机、为期4周的交叉喂养研究设计，使用在华盛顿大学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%的碳水化合物或20EN%的脂肪。65en%的碳水化合物和等量的蛋白质(15en%)和饱和脂肪(8en%)。体重将保持稳定。资格标准是甘油三酯150 mg/dl和甲硫氨酸的任何两个其他标准。72名男性和女性将随机产生60名完成测试的受试者，辍学率为20%。从GCRC取食物时，体重和其他生命体征将每周测量两次。分别于0周、3周、4周测定血脂。分别于0周和4周检测载脂蛋白B和A-L、低密度脂蛋白浮力、血糖、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个月将继续在营养师咨询下进行第二次饮食分配，并进行重复测试。预期结果：与20en%的脂肪饮食相比，METS受试者40en%的脂肪饮食将在非高密度脂蛋白胆固醇、其他脂蛋白和血糖变量、炎症和臂部反应性方面产生改善。这项研究将首次证明饮食有益于稳定体重的蛋氨酸患者的血脂紊乱、炎症和血管应激。

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.