Robert S. Rosenson教授 美国Mount Sinai医学院

　　<International Circulation>:Cardiometabolic disorder is one of the most important types of pathogenesis regarding cardiac dysfunction. As an expert in this field， could you please talk about what advances have been made with regard to cardiometabolic disorders? What is the clinical significance? Are there currently any effective clinical strategies for the treatment of cardiometabolic disorder? What about the main direction and future prospects in the field?

　　Prof. Rosenson: The underlying pathophysiology that is responsible for current metabolic risk is insulin resistance that most often occurs from visceral adiposity， and conditions such as polycystic ovarian disease. The strategies that we use are directed toward weight loss and selection of foods that are high in soluble fibers， low in saturated fat and refined carbohydrates， and we emphasize aerobic fitness through the performance of regular， moderate to intense exercise， at a minimum of three hours per week.

　　There are therapies that have been shown to prevent the progression of type 2 diabetes in people with central obesity， such as metformin. But structured weight loss programs through diet and exercise are actually superior to metformin in reducing the progression of type 2 diabetes.

　　With regards to diagnostics， high triglycerides and low HDL cholesterol are important predictors of the future risk of type 2 diabetes as we showed in the women’s health study. But， approaching subclasses provides more information. Specifically， large VLDL particles， high concentrations of small particles and low concentrations of HDL particles are particularly informative about those individuals who are at highest risk for progressing onto type 2 diabetes and also having a cardiovascular event.

　　Using this information， we’ve learned that DLDL cholesterol， which is not a component of cardiometabolic risk， does underrepresent the risk associated with high circulating levels of DLDL particles. So， in patients who have central obesity， metabolic syndrome， DLDL particles are triglyceride enriched and cholesterol depleted. These small DLDL particles don’t interact with the DLDL receptors as effectively as the large particles， thus they circulate in the bloodstream for a longer period of time， more likely to become oxidized or chemically modified， including glycated. That actually increases their oxidative susceptibility and role in increasing vascular inflammation. So there has been multiple expert consensus documents， from the American Diabetes Association， the American College of Cardiology， the American Academy of Clinical Chemists and the National Lipid Association that have suggested that one should evaluate lipoprotein particle concentration in people at high cardiometabolic risk， and then target therapy based on that information.

　　《国际循环》：心肌代谢障碍是心功能不全的重要发病机制之一。作为这个领域的专家，您能否介绍一下，目前关于心肌代谢障碍的研究取得了哪些进展？其临床意义是什么？目前有无有效的临床心脏代谢紊乱治疗策略？该领域未来发展的主要方向和前景如何？

　　Rosenson教授：目前引发代谢风险的基本病理生理机制是胰岛素抵抗，其最常见于内脏肥胖以及多囊卵巢疾病等情况下出现。我们所采用的治疗策略主要是以减重及选择富含可溶性纤维而饱和脂肪酸及精制碳水化合物含量较低的食物为主。我们强调通过每周至少3小时的、中度至高强度的体育锻炼进行有氧健身运动。

　　有研究显示，二甲双胍等治疗措施能预防中央型肥胖患者2型糖尿病的进展。但实际上，通过饮食及运动的结构性减重计划预防2型糖尿病进展的作用要优于二甲双胍。

　　就诊断而言，正如妇女健康研究所示，高甘油三酯及低HDL-C是未来2型糖尿病风险的重要预测因素。而进一步的分类则能为我们提供更多的信息。具体来说，较大的VLDL颗粒、高浓度的小颗粒及低浓度的HDL颗粒对高危患者进展为2型糖尿病及发生心血管事件更具预测价值。

　　通过上述信息，我们可得知DLDL-C不是心脏代谢风险的组分，无法充分代表与较高的DLDL颗粒水平相关的风险。因此，在伴有中央型肥胖、代谢综合征的患者中，DLDL颗粒中富含甘油三酯，但胆固醇含量较低。与大DLDL颗粒相比，这些小的DLDL颗粒不能有效作用于DLDL受体，因此在血流中能循环更长时间，更易被氧化或被糖基化等化学修饰。这实际上可增加其氧化易感性及其在血管炎症中的作用。因此，已有包括美国糖尿病协会（ADA）、美国心脏病学学会（ACC）、美国临床化学学会及国家脂质协会在内的多个组织出台了专家共识文件，推荐对心脏代谢高危患者进行脂蛋白颗粒评估，并根据评估结果进行有针对性的治疗。