Giles Thomas D, Sander Gary E
Section of Cardiology, Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Curr Hypertens Rep. 2007 Aug;9(4):332-7. doi: 10.1007/s11906-007-0060-0.
Peroxisome-proliferator-activated receptor-gamma (PPAR-gamma) agonists (known as thiazolidinediones; TDZs) activate nuclear receptors that regulate gene expression; they were developed as insulin-sensitizing drugs to treat type 2 diabetes mellitus. Although the prototypic TZD troglitazone was withdrawn from the market due to hepatic toxicity, rosiglitazone and pioglitazone are mainstays in managing type 2 diabetes mellitus. TZDs exert their hypoglycemic effect by reducing insulin resistance, hence improving insulin sensitivity. However, TZDs also exhibit a broad range of cardiovascular actions, with the clinical consequence of reduction in blood pressure (BP), observed in animal models and human diabetic subjects. The magnitude of reduction appears to be about 4 to 5 mm Hg in systolic and 2 to 4 mm Hg in diastolic BP--sufficient to significantly reduce subsequent cardiovascular event rates. But these BP-reducing properties, which are not present with metformin or sulfonylureas, are particularly important when viewed in conjunction with hypoglycemic effects. A significant proportion of patients with type 2 diabetes mellitus and BP mildly above target range might be successfully treated for both processes with a single drug.
过氧化物酶体增殖物激活受体γ（PPAR-γ）激动剂（即噻唑烷二酮类药物；TDZs）可激活调节基因表达的核受体；它们作为胰岛素增敏药物被开发用于治疗2型糖尿病。尽管原型噻唑烷二酮类药物曲格列酮因肝毒性已退出市场，但罗格列酮和吡格列酮仍是治疗2型糖尿病的主要药物。噻唑烷二酮类药物通过降低胰岛素抵抗发挥降糖作用，从而提高胰岛素敏感性。然而，噻唑烷二酮类药物还表现出广泛的心血管作用，在动物模型和糖尿病患者中观察到其临床后果是血压（BP）降低。收缩压降低幅度约为4至5毫米汞柱，舒张压降低幅度约为2至4毫米汞柱——足以显著降低后续心血管事件发生率。但与二甲双胍或磺脲类药物不同，噻唑烷二酮类药物的这些降压特性与降糖作用相结合时尤为重要。相当一部分2型糖尿病且血压略高于目标范围的患者可能使用单一药物就能成功治疗这两个问题。
