Lebovitz Harold E
Division of Endocrinology and Metabolism/Diabetes, State University of New York, Health Science Center, Brooklyn, NY, USA.
Diabetes Obes Metab. 2006 May;8(3):237-49. doi: 10.1111/j.1463-1326.2005.00521.x.
Evidence suggests that diabetes and cardiovascular disease (CVD) may share an underlying cause(s), a theory known as the 'common soil' hypothesis. Insulin resistance is central both to the progression from normal glucose tolerance to type 2 diabetes and to a constellation of cardiovascular risk factors known as the metabolic syndrome. These risk factors include visceral obesity and dyslipidaemia characterized by low levels of high-density lipoprotein cholesterol, hypertriglyceridaemia and raised small dense low-density lipoprotein particle levels. Changes in adipose tissue mass and metabolism may link insulin resistance and visceral obesity, a condition that is common in type 2 diabetes. Furthermore, weight reduction, increased physical activity, metformin and acarbose have been shown to reduce the development of type 2 diabetes in genetically predisposed subjects and may decrease the high cardiovascular risk of patients with diabetes. Some fatty acid derivatives can affect energy metabolism by activating peroxisome proliferator-activated receptors (PPARs), nuclear receptors that play a key role in energy homeostasis. These receptors represent an ideal therapeutic target for reducing cardiovascular risk, because they are involved in the regulation of both insulin action and lipid metabolism. In addition to lifestyle changes, PPARgamma agonists such as thiazolidinediones are frequently beneficial and have been shown to ameliorate insulin resistance, while activation of PPARalpha (e.g. by fibrates) can lead to improvements in free fatty acid oxidation and lipid profile, and a reduction in cardiovascular events. The development of agents with both PPARalpha and PPARgamma activity promises added benefits with amelioration of insulin resistance, delayed progression to and of type 2 diabetes and a reduction of CVD.
有证据表明，糖尿病和心血管疾病（CVD）可能有共同的潜在病因，这一理论被称为“共同土壤”假说。胰岛素抵抗在从正常糖耐量进展为2型糖尿病以及一系列被称为代谢综合征的心血管危险因素中都起着核心作用。这些危险因素包括内脏肥胖和血脂异常，其特征为高密度脂蛋白胆固醇水平低、高甘油三酯血症以及小而密的低密度脂蛋白颗粒水平升高。脂肪组织质量和代谢的变化可能将胰岛素抵抗与内脏肥胖联系起来，而内脏肥胖在2型糖尿病中很常见。此外，减肥、增加体力活动、使用二甲双胍和阿卡波糖已被证明可降低遗传易感性个体患2型糖尿病的风险，并可能降低糖尿病患者的高心血管疾病风险。一些脂肪酸衍生物可通过激活过氧化物酶体增殖物激活受体（PPARs）来影响能量代谢，PPARs是在能量稳态中起关键作用的核受体。这些受体是降低心血管疾病风险的理想治疗靶点，因为它们参与胰岛素作用和脂质代谢的调节。除了生活方式改变外，噻唑烷二酮类等PPARγ激动剂通常有益，已被证明可改善胰岛素抵抗，而激活PPARα（如通过贝特类药物）可改善游离脂肪酸氧化和血脂水平，并减少心血管事件。同时具有PPARα和PPARγ活性的药物的开发有望在改善胰岛素抵抗、延缓2型糖尿病的发生和发展以及降低心血管疾病方面带来更多益处。
