Greenfield Jerry R, Campbell Lesley V
Diabetes and Obesity Research Program, Garvan Institute of Medical Research, Sydney, Australia.
Curr Diabetes Rev. 2006 May;2(2):195-211. doi: 10.2174/157339906776818532.
Inflammation has been implicated as an important aetiological factor in the development of both insulin resistance and type 2 diabetes mellitus. This conclusion is predominantly drawn from studies demonstrating associations between elevated (but 'normal range') levels of circulating acute phase inflammatory markers, typified by C-reactive protein (CRP), and indices of insulin resistance and the development of type 2 diabetes. There is debate as to whether these associations are independent of body fatness or, rather, an epiphenomenon of obesity, particularly central obesity, a strong predictor of insulin resistance and type 2 diabetes and an important source of inflammatory cytokines, such as interleukin-6. Some of this controversy and the inability to draw definitive conclusions from these studies relate to the fact that most studies measure body fat and its distribution indirectly using anthropometric estimates, such as Body Mass Index and waist circumference, rather than directly by dual-energy X-ray absorptiometry, computed tomography or magnetic resonance imaging. Furthermore, use of the term inflammation may be inappropriate when describing mild elevations of CRP in the 'normal range' in the absence of the other changes that characterise classical inflammatory diseases, such as a reduction in levels (or evidence of consumption) of complement proteins. Debate as to whether obesity mediates the association between circulating levels of inflammatory markers and insulin resistance can be resolved by well-designed studies using body fat measured by gold-standard methods. In this review, we present evidence to support the suggestion that body fat is the primary determinant of circulating inflammatory marker levels in the basal state and that marginally elevated levels of circulating interleukin-6 and CRP in obesity are a consequence rather than a cause of insulin resistance. The importance of genetic influences in determining both body fatness and circulating CRP levels will also be discussed. The review will conclude with a discussion of possible mechanisms linking body fat and insulin resistance to elevated circulating levels of inflammatory markers, including the possible role of the toll-like family of immune receptors.
炎症被认为是胰岛素抵抗和2型糖尿病发生发展的重要病因。这一结论主要来自于一些研究，这些研究表明循环中急性期炎症标志物水平升高（但仍在“正常范围”）与胰岛素抵抗指标及2型糖尿病的发生之间存在关联，其中以C反应蛋白（CRP）为典型代表。关于这些关联是独立于体脂，还是肥胖（尤其是中心性肥胖）的一种附带现象，存在争议。中心性肥胖是胰岛素抵抗和2型糖尿病的有力预测指标，也是白细胞介素-6等炎症细胞因子的重要来源。部分争议以及无法从这些研究中得出明确结论，与以下事实有关：大多数研究使用人体测量估计值（如体重指数和腰围）间接测量体脂及其分布，而非通过双能X线吸收法、计算机断层扫描或磁共振成像直接测量。此外，在没有典型炎症疾病特征性的其他变化（如补体蛋白水平降低或消耗证据）的情况下，用“炎症”一词来描述CRP在“正常范围”内的轻度升高可能并不恰当。关于肥胖是否介导炎症标志物循环水平与胰岛素抵抗之间的关联的争议，可以通过使用金标准方法测量体脂的精心设计的研究来解决。在本综述中，我们提供证据支持以下观点：体脂是基础状态下循环炎症标志物水平的主要决定因素，肥胖时循环中白细胞介素-6和CRP水平的轻微升高是胰岛素抵抗的结果而非原因。还将讨论基因影响在决定体脂和循环CRP水平方面的重要性。综述将以讨论将体脂和胰岛素抵抗与炎症标志物循环水平升高联系起来的可能机制作为结尾，包括Toll样免疫受体家族可能发挥的作用。
