Fiévet Catherine, Staels Bart
Institut Pasteur, Lille, France.
Curr Atheroscler Rep. 2009 Jul;11(4):281-8. doi: 10.1007/s11883-009-0043-5.
The greatest clinical challenge in type 2 diabetes mellitus is the prevention of its long-term complications, many of which are of a cardiovascular nature. Despite the progress in cardiovascular risk management of diabetes patients using lipid-lowering and antihypertensive drugs, a substantial residual risk persists. Indeed, treated diabetes patients have a similar risk as untreated nondiabetic individuals. Although glycemic control through the use of antihyperglycemic agents improves microvascular complications, macrovascular disease risk is not reduced. These observations point to the need for additional therapeutic approaches in order to better control global cardiovascular risk. The peroxisome proliferator-activated receptor (PPAR) family members play major roles in the regulation of lipid and glucose metabolism and immune-inflammatory processes, making these transcription factors ideal targets for such therapeutic strategies. This review discusses our current knowledge of the effectiveness of PPAR-based therapeutics, focusing exclusively on cardiovascular disease in type 2 diabetes mellitus and the future prospects for novel generation of PPAR agonists.
2型糖尿病最大的临床挑战在于预防其长期并发症，其中许多并发症具有心血管性质。尽管在使用降脂和抗高血压药物对糖尿病患者进行心血管风险管理方面取得了进展，但仍存在相当大的残余风险。事实上，接受治疗的糖尿病患者与未接受治疗的非糖尿病个体具有相似的风险。虽然通过使用降糖药物进行血糖控制可改善微血管并发症，但大血管疾病风险并未降低。这些观察结果表明需要额外的治疗方法，以便更好地控制整体心血管风险。过氧化物酶体增殖物激活受体（PPAR）家族成员在脂质和葡萄糖代谢以及免疫炎症过程的调节中起主要作用，使这些转录因子成为此类治疗策略的理想靶点。本综述讨论了我们目前对基于PPAR的治疗方法有效性的认识，特别关注2型糖尿病中的心血管疾病以及新一代PPAR激动剂的未来前景。
