Diabetes and Cardiovascular Center, University of Missouri School of Medicine, Columbia, MO, USA.
Division of Endocrinology and Metabolism, Department of Medicine, University of Missouri-Columbia School of Medicine, One Hospital Drive, Columbia, MO, 65212, USA.
Cardiovasc Diabetol. 2018 Apr 18;17(1):59. doi: 10.1186/s12933-018-0704-1.
Multiple population based analyses have demonstrated a high incidence of cardiovascular disease (CVD) and cardiovascular (CV) mortality in subjects with T2DM that reduces life expectancy by as much as 15 years. Importantly, the CV system is particularly sensitive to the metabolic and immune derangements present in obese pre-diabetic and diabetic individuals; consequently, CV dysfunction is often the initial CV derangement to occur and promotes the progression to end organ/tissue damage in T2DM. Specifically, diabetic CVD can manifest as microvascular complications, such as nephropathy, retinopathy, and neuropathy, as well as, macrovascular impairments, including ischemic heart disease, peripheral vascular disease, and cerebrovascular disease. Despite some progress in prevention and treatment of CVD, mainly via blood pressure and dyslipidemia control strategies, the impact of metabolic disease on CV outcomes is still a major challenge and persists in proportion to the epidemics of obesity and diabetes. There is abundant pre-clinical and clinical evidence implicating the DPP-4-incretin axis in CVD. In this regard, linagliptin is a unique DPP-4 inhibitor with both CV and renal safety profiles. Moreover, it exerts beneficial CV effects beyond glycemic control and beyond class effects. Linagliptin is protective for both macrovascular and microvascular complications of diabetes in preclinical models, as well as clinical models. Given the role of endothelial-immune cell interactions as one of the key events in the initiation and progression of CVD, linagliptin modulates these cell-cell interactions by affecting two important pathways involving stimulation of NO signaling and potent inhibition of a key immunoregulatory molecule.
多项基于人群的分析表明，2 型糖尿病患者心血管疾病 (CVD) 和心血管 (CV) 死亡率较高，使预期寿命缩短多达 15 年。重要的是，CV 系统对肥胖前期糖尿病和糖尿病个体中存在的代谢和免疫紊乱特别敏感；因此，CV 功能障碍通常是最初发生的 CV 紊乱，并促进 2 型糖尿病向终末器官/组织损伤的进展。具体而言，糖尿病性 CVD 可表现为微血管并发症，如肾病、视网膜病变和神经病，以及大血管损伤，包括缺血性心脏病、外周血管疾病和脑血管疾病。尽管在 CVD 的预防和治疗方面取得了一些进展，主要通过血压和血脂异常控制策略，但代谢疾病对 CV 结局的影响仍然是一个主要挑战，并且与肥胖和糖尿病的流行成正比。有大量的临床前和临床证据表明 DPP-4-肠促胰岛素轴与 CVD 有关。在这方面，利格列汀是一种独特的 DPP-4 抑制剂，具有 CV 和肾脏安全性。此外，它除了血糖控制和类效应之外，还具有有益的 CV 作用。利格列汀在临床前和临床模型中对糖尿病的大血管和微血管并发症均具有保护作用。鉴于内皮-免疫细胞相互作用作为 CVD 起始和进展的关键事件之一，利格列汀通过影响涉及刺激 NO 信号和有效抑制关键免疫调节分子的两个重要途径来调节这些细胞-细胞相互作用。
