Relationship Between Inflammation, Insulin Resistance and Type 2 Diabetes: 'Cause or Effect'?
Relationship Between Inflammation, Insulin Resistance and Type 2 Diabetes: 'Cause or Effect'?
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DOI：
10.2174/157339906776818532
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发表时间：
2006-01-01
影响因子：
3.3
通讯作者：
Campbell, Lesley V.
中科院分区：
文献类型：
--
作者：
Greenfield, Jerry R.;Campbell, Lesley V.
炎症已被认为是胰岛素抵抗和2型糖尿病发展的重要病因因素。这一结论主要来自于证明循环急性期炎症标志物（以C反应蛋白（CRP）为代表）水平升高（但“正常范围”）与胰岛素抵抗指数和2型糖尿病发展之间相关性的研究。关于这些关联是否独立于身体肥胖，或者更确切地说，是肥胖的附带现象，特别是中心性肥胖，是胰岛素抵抗和2型糖尿病的强预测因子，也是炎性细胞因子（如白细胞介素-6）的重要来源，存在争议。一些争议和无法从这些研究中得出明确的结论与以下事实有关：大多数研究使用人体测量估计间接测量体脂及其分布，如体重指数和腰围，而不是直接通过双能X射线吸收法，计算机断层扫描或磁共振成像。此外，当描述CRP在“正常范围”内的轻度升高，而不存在其他改变时，使用术语炎症可能是不合适的，这些改变会导致典型的炎症性疾病，例如补体蛋白水平降低（或消耗证据）。关于肥胖是否介导了炎症标志物循环水平与胰岛素抵抗之间的关联的争论，可以通过设计良好的研究来解决，这些研究使用金标准方法测量体脂。在这篇综述中，我们提出的证据支持的建议，体脂是基础状态下的循环炎症标志物水平的主要决定因素，并认为轻微升高的循环白细胞介素-6和CRP水平的肥胖是一个后果，而不是胰岛素抵抗的原因。遗传因素在决定身体肥胖和循环CRP水平方面的重要性也将被讨论。该综述将以讨论将体脂和胰岛素抵抗与炎症标志物的循环水平升高联系起来的可能机制作为结论，包括免疫受体的toll样家族的可能作用。
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.