Dokken Betsy
Betsy Dokken, NP, PhD, CDE Assistant Professor of Medicine, Section of Endocrinology and Diabetes Research Program, University of Arizona, Tucson.
J Cardiovasc Nurs. 2016 May-Jun;31(3):274-83. doi: 10.1097/JCN.0000000000000245.
Cardiovascular (CV) disease is the major cause of mortality and morbidity in patients with type 2 diabetes mellitus (T2DM). The pathogenesis of CV disease in T2DM is complex and multifactorial and involves direct and indirect injury to the vasculature and heart. The impact of intensive glucose-lowering therapy with antihyperglycemic agents on CV outcomes is not clear, and questions remain as to which glucose-lowering agents may be beneficial to CV health in patients with T2DM.
This review discusses findings regarding the known mechanisms of CV injury in T2DM and current knowledge regarding the potential cardioprotective effects of dipeptidyl peptidase-4 (DPP-4) inhibitors.
Dipeptidyl peptidase-4 inhibitors are relatively new antihyperglycemic agents. Their main mechanism of action is to inhibit the degradation of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic peptide by DPP-4. By increasing levels of glucagon-like peptide-1, glucose-dependent insulin secretion is enhanced, glucagon secretion is suppressed, and the rate of gastric emptying is decreased. Dipeptidyl peptidase-4 also degrades other substances that are important in the regulation of CV function and inflammation. Animal studies, small observational studies in humans, and analyses of clinical trial data suggest that DPP-4 inhibitors may have beneficial CV effects. Recent prospectively designed CV outcomes trials with saxagliptin and alogliptin in patients with T2DM and high CV risk presented evidence that these DPP-4 inhibitors neither increased nor decreased adverse CV outcomes in this select patient population.
Dipeptidyl peptidase-4 inhibitors are promising therapies for the treatment of T2DM. Able to improve glycemic control without the risk of weight gain or hypoglycemia, they provide a safe alternative to sulfonylureas and are an effective adjunct to metformin. To date, this class of drugs seems to be at least neutral in terms of CV effects. Time will tell if these findings translate into a benefit for our patients.
心血管（CV）疾病是2型糖尿病（T2DM）患者发病和死亡的主要原因。T2DM患者CV疾病的发病机制复杂且多因素，涉及对血管系统和心脏的直接和间接损伤。使用降糖药物进行强化降糖治疗对CV结局的影响尚不清楚，对于哪些降糖药物可能有益于T2DM患者的CV健康仍存在疑问。
本综述讨论了关于T2DM中CV损伤的已知机制的研究结果以及关于二肽基肽酶-4（DPP-4）抑制剂潜在心脏保护作用的当前知识。
DPP-4抑制剂是相对较新的降糖药物。它们的主要作用机制是抑制DPP-4对肠促胰岛素激素胰高血糖素样肽-1和葡萄糖依赖性促胰岛素多肽的降解。通过提高胰高血糖素样肽-1水平，增强葡萄糖依赖性胰岛素分泌，抑制胰高血糖素分泌，并降低胃排空速率。DPP-4还降解其他在CV功能和炎症调节中起重要作用的物质。动物研究、小型人体观察性研究以及临床试验数据分析表明，DPP-4抑制剂可能具有有益的CV效应。最近在T2DM和高CV风险患者中使用沙格列汀和阿格列汀进行的前瞻性设计的CV结局试验提供了证据，表明这些DPP-4抑制剂在该特定患者群体中既未增加也未降低不良CV结局。
DPP-4抑制剂是治疗T2DM的有前景的疗法。它们能够改善血糖控制而无体重增加或低血糖风险，为磺脲类药物提供了安全的替代方案，并且是二甲双胍的有效辅助药物。迄今为止，这类药物在CV效应方面似乎至少是中性的。时间将证明这些发现是否会给我们的患者带来益处。
