Schneider Christian A
Department III of Internal Medicine, University of Cologne, Cologne, Germany.
Curr Med Res Opin. 2006;22 Suppl 2:S15-26. doi: 10.1185/030079906X112723.
Type 2 diabetes is accompanied by a host of potentially modifiable cardiovascular disease risk factors. Consequently, people with type 2 diabetes have a higher risk of macrovascular disease than the non-diabetic population, and a poor prognosis following an event. Several large-scale primary and secondary outcome studies have included large diabetes subgroups for post-hoc analysis, and a limited number of studies have focused specifically on type 2 diabetes.
This review provides an overview of macrovascular outcome studies in type 2 diabetes and discusses potential new targets for therapy based upon a MEDLINE literature search from January 1990 to April 2006.
Large cardiovascular outcome studies show that treating cardiovascular disease risk factors significantly reduces the risk of primary and secondary macrovascular events in patients with type 2 diabetes. The evidence for targeting hypertension (using renin-angiotensin system inhibitors), dyslipidemia (statins), and coagulation factors (aspirin) appears robust. However, the macrovascular benefits of improved glucose control remain to be proven definitively, although metformin may have advantages over other glucose-lowering agents. Nevertheless, these studies reveal that significant excess residual risk remains, highlighting the need for new therapies. It is also apparent that some agents (e.g. metformin, statins, renin-angiotensin system inhibitors) may also have pleiotropic mechanisms. Newer strategies are investigating other lipid targets (especially HDL cholesterol) or using agents, such as thiazolidinediones, that address multiple established and emerging risk factors. A recent study with pioglitazone suggests that macrovascular risk can be reduced in very high-risk patients with type 2 diabetes who are already receiving contemporary lipid, anti-hypertensive, and anti-platelet therapy.
The core therapeutic paradigm targeting glycemia, hypertension, dyslipidemia, and coagulation factors has failed to remove excess residual risk in patients with type 2 diabetes completely. Emerging data, and on-going trials, should provide better guidance on new therapeutic opportunities in this high-risk patient group.
2型糖尿病伴有许多潜在可改变的心血管疾病危险因素。因此，2型糖尿病患者发生大血管疾病的风险高于非糖尿病人群，且发病后的预后较差。几项大规模的主要和次要结局研究纳入了大型糖尿病亚组进行事后分析，仅有少数研究专门针对2型糖尿病。
本综述基于1990年1月至2006年4月的MEDLINE文献检索，概述了2型糖尿病大血管结局研究，并讨论了潜在的新治疗靶点。
大型心血管结局研究表明，治疗心血管疾病危险因素可显著降低2型糖尿病患者发生原发性和继发性大血管事件的风险。针对高血压（使用肾素-血管紧张素系统抑制剂）、血脂异常（他汀类药物）和凝血因子（阿司匹林）的证据似乎很充分。然而，改善血糖控制对大血管的益处仍有待明确证实，尽管二甲双胍可能比其他降糖药物更具优势。尽管如此，这些研究表明仍存在显著的残余风险，凸显了新疗法的必要性。同样明显的是，一些药物（如二甲双胍、他汀类药物、肾素-血管紧张素系统抑制剂）可能还具有多效性机制。新的策略正在研究其他脂质靶点（尤其是高密度脂蛋白胆固醇）或使用噻唑烷二酮类等药物，这些药物可针对多种已确定和新出现的危险因素。一项最近关于吡格列酮的研究表明，对于已经接受现代脂质、抗高血压和抗血小板治疗的2型糖尿病高危患者，大血管风险可以降低。
针对血糖、高血压、血脂异常和凝血因子的核心治疗模式未能完全消除2型糖尿病患者的残余风险。新出现的数据以及正在进行的试验应能为这一高危患者群体的新治疗机会提供更好的指导。
