DIETS FOR DYSLIPIDEMIA IN THE METABOLIC SYNDROME

描述（由申请人提供）：代谢综合征（MetS）由一系列植根于当前肥胖流行的心血管风险因素组成。MetS的两个定义特征是高甘油三酯和低HDL，即MetS的血脂异常。这种血脂异常的标准卫生建议是减肥和运动，但在体重稳定时，对于最适合血脂异常或MetS相关血管反应性受损的饮食脂肪和碳水化合物比例没有共识。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，高脂肪，低碳水化合物摄入量与肥胖者的甘油三酯水平较低有关，但脂蛋白，炎症和血管反应的饮食干扰体重稳定性（通常的生理状态）尚未进行前瞻性研究。在血脂异常人群中，标准低脂、高碳水化合物饮食产生的LDL降低是单纯高胆固醇血症人群的1/3。这些人也对高饱和脂肪喂养不太敏感。与这些发现相一致的是，在观察性研究中，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学推理提出了以下假设：在MetS中，较高的脂肪摄入量比传统的限脂饮食更有益于：1）管理血脂异常，2）减少炎症应激和3）纠正内皮介导的血管反应性，动脉粥样硬化应激的直接指标。本研究将采用华盛顿大学GCRC代谢厨房制备的食物，采用随机、4周、交叉、喂养研究设计，比较脂肪和碳水化合物含量不同的两种饮食对脂蛋白和血管的影响。饮食将含有40en%的脂肪。45en%碳水化合物或20en%脂肪。65en%的碳水化合物与等量的蛋白质（15en%）和饱和脂肪（8en%）。体重将保持稳定。合格标准是甘油三酯> 150 mg/dl和MetS的任何两个其他标准。将对72名男性和女性进行随机化，以产生60名完成研究的受试者，脱落率为20%。当从GCRC取食物时，每周测量两次体重和其他生命体征。将在第0、3和4周测量脂蛋白脂质。在0周和4周时测量载脂蛋白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。4个月的延长将继续第二次饮食分配下营养师咨询与重复测试。预期成果：与20en%脂肪相比，MetS受试者中的40en%脂肪饮食将产生非HDL-C、其他脂蛋白和血糖变量、炎症和肱动脉反应性的改善。这项研究将是第一个证明饮食对体重稳定的MetS血脂异常、炎症和血管应激有益的研究。

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.