Cardiovascular Comorbidities of Type 2 Diabetes Mellitus: Defining the Potential of Glucagonlike peptide-1-Based Therapies
Cardiovascular Comorbidities of Type 2 Diabetes Mellitus: Defining the Potential of Glucagonlike peptide-1-Based Therapies
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DOI：
10.1016/j.amjmed.2010.11.004
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发表时间：
2011-01-01
影响因子：
5.9
通讯作者：
Lujan, Michael
中科院分区：
文献类型：
--
作者：
Chilton, Robert;Wyatt, Jamison;Lujan, Michael
糖尿病（类似于95%的2型糖尿病）的全球流行受到肥胖和超重的平行增加的推动。总之，这些代谢性疾病的流行导致了心血管疾病发病率和患病率的增加。代谢和心血管危险因素在2型糖尿病患者中的积累--这些危险因素可能相互加重--使治疗复杂化。治疗不足，治疗未能达到目标，增加了心血管发病率和死亡率的风险。从临床角度来看，2型糖尿病是一种心血管疾病，这一观察结果得到了一系列流行病学、尸检和心血管成像研究的支持。血管壁功能障碍，特别是内皮功能障碍，已被认为是一个“共同的土壤”连接血糖异常和心血管疾病。血管壁功能障碍促进环境触发（e。例如，在一个实施例中，久坐不动的生活方式）和代谢触发因素（慢性高血糖症、肥胖症）与活性氧物质和慢性炎症和高凝状态的上调有关，因此与2型糖尿病、动脉粥样硬化和心血管疾病的发病机制有关。胰高血糖素样肽-1（GLP）-1（一种肠促胰岛素激素）和合成GLP-1受体激动剂代表了不仅在对抗2型糖尿病而且在对抗与2型糖尿病相关的心血管发病率和死亡率方面有前途的研究和治疗新领域。在许多人体小型试验以及临床前和体外研究中，天然GLP-1和GLP-1受体激动剂均对一系列心血管疾病病理和临床靶点（包括血管炎症标志物，如高敏C反应蛋白、纤溶酶原激活物抑制剂-1和脑利钠肽）具有积极作用。还观察到血脂异常标志物减少，如甘油三酯和游离脂肪酸水平升高，具有心脏保护功能。需要进行更长时间的大型试验，以确认初步结果。在大型人体试验中，GLP-1受体激动剂与血压和体重显著降低相关。(C)2011 Elsevier Inc. All rights reserved.美国医学杂志（2011）124，S35-S53
The global epidemic of diabetes mellitus (similar to 95% type 2 diabetes) has been fueled by a parallel increase in obesity and overweight. Together, these metabolic disease epidemics have contributed to the increasing incidence and prevalence of cardiovascular disease. The accumulation of metabolic and cardiovascular risk factors in patients with type 2 diabetes-risk factors that may exacerbate one another-complicates treatment. Inadequate treatment, treatment that fails to achieve goals, increases the risk for cardiovascular morbidity and mortality. From a clinical perspective, type 2 diabetes is a cardiovascular disease, an observation that is supported by a range of epidemiologic, postmortem, and cardiovascular imaging studies. Vascular wall dysfunction, and particularly endothelial dysfunction, has been posited as a "common soil" linking dysglycemic and cardiovascular diseases. Vascular wall dysfunction promoted by environmental triggers (e. g., sedentary lifestyle) and metabolic triggers (chronic hyperglycemia, obesity) has been associated with the upregulation of reactive oxygen species and chronic inflammatory and hypercoagulable states, and as such with the pathogenesis of type 2 diabetes, atherosclerosis, and cardiovascular disease. Glucagon-like peptide-1 (GLP)-1, an incretin hormone, and synthetic GLP-1 receptor agonists represent promising new areas of research and therapeutics in the struggle not only against type 2 diabetes but also against the cardiovascular morbidity and mortality associated with type 2 diabetes. In a number of small trials in humans, as well as in preclinical and in vitro studies, both native GLP-1 and GLP-1 receptor agonists have demonstrated positive effects on a range of cardiovascular disease pathologies and clinical targets, including such markers of vascular inflammation as high-sensitivity C-reactive protein, plasminogen activator inhibitor-1, and brain natriuretic peptide. Reductions in markers of dyslipidemia such as elevated levels of triglycerides and free fatty acids have also been observed, as have cardioprotective functions. Larger trials of longer duration will be required to confirm preliminary findings. In large human trials, GLP-1 receptor agonists have been associated with significant reductions in both blood pressure and weight. (C) 2011 Elsevier Inc. All rights reserved. The American Journal of Medicine (2011) 124, S35-S53