Yudkin J S
Department of Medicine, University College London, Archway Campus, Highgate Hill, London, UK.
Diabetologia. 2007 Aug;50(8):1576-86. doi: 10.1007/s00125-007-0711-3. Epub 2007 Jun 26.
The clustering of dyslipidaemia, hypertension and glucose intolerance, predominantly in overweight individuals, has been ascribed many names, including syndrome X and the metabolic syndrome. In Reaven's original description of syndrome X, a central aetiological role was attributed to insulin resistance, and this assumption has remained as the dominant paradigm for the metabolic syndrome. There are a number of conceptual problems in such a model, particularly those arising from observations that several novel markers, including measures of endothelial dysfunction and of low-grade inflammation, are as closely related to insulin resistance as are the classic components of the syndrome. Because it is difficult to envisage how these traits might develop as a consequence of insulin resistance, such observations indicate the need for a new paradigm to explain the mechanisms of association better. It has been proposed that a state of low-grade inflammation, consequent upon the production of adipocytokines, particularly from truncal fat, explains the observed relationships between insulin resistance and endothelial dysfunction better than does a model revolving around insulin resistance. Furthermore, the inflammatory cytokines generated from adipose tissue may influence vessel endothelial function without elevations in circulating concentrations. This review alludes to several problems inherent in the epidemiological method in understanding disease mechanisms. These include crude biological measures, the use of venous systemic fasting samples, imprecision of assays, naive physiological models, simplistic statistical approaches and, without clinical trials, an inability to test causation. Integrated systems biology needs more complex approaches to investigate disease mechanisms, involving cell, organ, whole organism and population studies.
血脂异常、高血压和糖耐量异常的聚集现象主要出现在超重个体中，它有许多名称，包括X综合征和代谢综合征。在雷文对X综合征的最初描述中，胰岛素抵抗被认为起着核心病因作用，这一假设一直是代谢综合征的主导范式。这种模型存在一些概念性问题，特别是那些源于以下观察结果的问题：包括内皮功能障碍和低度炎症指标在内的一些新标记物与胰岛素抵抗的关系，与该综合征的经典组成部分一样密切。由于很难设想这些特征如何因胰岛素抵抗而发展，这些观察结果表明需要一个新的范式来更好地解释其关联机制。有人提出，由脂肪细胞因子产生，特别是来自躯干脂肪的脂肪细胞因子所导致的低度炎症状态，比围绕胰岛素抵抗的模型更能解释胰岛素抵抗与内皮功能障碍之间的观察到的关系。此外，脂肪组织产生的炎性细胞因子可能在不升高循环浓度的情况下影响血管内皮功能。本综述提及了流行病学方法在理解疾病机制方面固有的几个问题。这些问题包括粗略的生物学测量、静脉系统空腹样本的使用、检测方法的不精确性、幼稚的生理模型、简单化的统计方法，以及在没有临床试验的情况下无法检验因果关系。整合系统生物学需要更复杂的方法来研究疾病机制，包括细胞、器官、整个生物体和人群研究。
