Kalofoutis Christos, Piperi Christina, Kalofoutis Anastasios, Harris Fred, Phoenix David, Singh Jaipaul
Department of Biological Chemistry, University of Athens, Athens, Greece.
Exp Clin Cardiol. 2007 Spring;12(1):17-28.
Worldwide, approximately 200 million people currently have type II diabetes mellitus (DM), a prevalence that has been predicted to increase to 366 million by 2030. Rates of cardiovascular disease (CVD) mortality and morbidity are particularly high in this population, representing a significant cost for health care systems. Type II DM patients generally carry a number of risk factors for CVD, including hyperglycemia, abnormal lipid profiles, alterations in inflammatory mediators and coagulation/thrombolytic parameters, as well as other 'nontraditional' risk factors, many of which may be closely associated with insulin resistance. Therefore, successful management of CVD associated with diabetes represents a major challenge to the clinicians. An effective way of tackling this problem is to detect the associated risk factors and to target treatment toward their improvement. Targeting hyperglycemia alone does not reduce the excess risk in diabetes, highlighting the need for aggressive treatment of other risk factors. Although the current use of statin therapy is effective at reducing low-density lipoprotein cholesterol, residual risk remains for other independent lipid and nonlipid factors. The peroxisome proliferator-activated receptor-gamma appears to be closely involved in regulating risk markers at multiple levels. A relatively new class of therapeutic agents that activate peroxisome proliferator-activated receptor-gamma, the thiazolidinedione insulin-sensitizing agents, is currently used to manage type II DM. These agents display a number of potential antiatherogenic properties, including effects on high-density lipoprotein cholesterol and triglycerides, as well as other beneficial nonlipid effects, such as regulating levels of mediators involved in inflammation and endothelial dysfunction. Research data suggest that simple strategies combining thiazolidinediones and statins could have complementary effects on CVD risk-factor profiles in diabetes, alongside the ability to control glycemia.
在全球范围内，目前约有2亿人患有II型糖尿病（DM），预计到2030年这一患病率将增至3.66亿。该人群中心血管疾病（CVD）的死亡率和发病率尤其高，给医疗保健系统带来了巨大成本。II型糖尿病患者通常存在多种CVD危险因素，包括高血糖、血脂异常、炎症介质和凝血/溶栓参数改变，以及其他“非传统”危险因素，其中许多可能与胰岛素抵抗密切相关。因此，成功管理与糖尿病相关的CVD对临床医生来说是一项重大挑战。解决这一问题的有效方法是检测相关危险因素并针对其改善进行治疗。仅针对高血糖并不能降低糖尿病患者的额外风险，这凸显了积极治疗其他危险因素的必要性。尽管目前使用他汀类药物治疗在降低低密度脂蛋白胆固醇方面有效，但其他独立的脂质和非脂质因素仍存在残余风险。过氧化物酶体增殖物激活受体γ似乎在多个层面密切参与调节风险标志物。一类相对较新的激活过氧化物酶体增殖物激活受体γ的治疗药物，即噻唑烷二酮类胰岛素增敏剂，目前用于管理II型糖尿病。这些药物具有多种潜在的抗动脉粥样硬化特性，包括对高密度脂蛋白胆固醇和甘油三酯的影响，以及其他有益的非脂质作用，如调节参与炎症和内皮功能障碍的介质水平。研究数据表明，将噻唑烷二酮类药物和他汀类药物联合使用的简单策略，除了能够控制血糖外，还可能对糖尿病患者的CVD危险因素谱产生互补作用。
