Incretin-based therapy: a powerful and promising weapon in the treatment of type 2 diabetes mellitus.
Incretin-based therapy: a powerful and promising weapon in the treatment of type 2 diabetes mellitus.
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DOI：
10.1007/s13300-011-0002-3
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发表时间：
2011-05
期刊：
影响因子：
3.8
通讯作者：
Doupis, John
中科院分区：
文献类型：
--
作者：
Koliaki, Chrysi;Doupis, John
2 型糖尿病 (T2DM) 是一种进行性多系统疾病，会显着增加心血管疾病的发病率和死亡率。它与肥胖、胰岛素抵抗、β细胞功能障碍和高胰高血糖素血症有关，这些因素的结合通常会导致高血糖。基于肠促胰素的治疗方式，特别是胰高血糖素样肽 1 (GLP-1) 受体激动剂，能够成功抵消 T2DM 的几种潜在病理生理异常。 GLP-1 受体激动剂的胰腺作用包括通过刺激胰岛素分泌和以严格葡萄糖依赖性方式抑制胰高血糖素释放来降低葡萄糖作用、增加 β 细胞增殖和减少 β 细胞凋亡。 GLP-1受体在人体中广泛表达；因此，基于 GLP-1 的疗法发挥的多效性和多系统效应远远超出了胰岛。大量实验和临床数据表明，GLP-1 类似物对心血管系统（降低血压、改善内皮和心肌功能、衰竭和缺血性心脏的功能恢复、动脉血管舒张）、肾脏（增加利尿和尿钠排泄）、胃肠道（延迟胃排空、减少胃酸）具有相当大的保护作用。 分泌）和中枢神经系统（食欲抑制，神经保护特性）。 GLP-1 受体激动剂的药理用途已被证明可以降低体重和收缩压，并显着改善血糖控制和血脂状况。有趣的是，GLP-1类似物引起的体重减轻主要反映了腹部内脏脂肪的减少。 GLP-1类似物所产生的积极心脏代谢作用是否可以转化为糖尿病患者在心血管发病率和死亡率等长期硬终点方面更好的临床结果，这一关键问题仍有待通过前瞻性、大规模临床试验来阐明。
Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease that increases significantly cardiovascular morbidity and mortality. It is associated with obesity, insulin resistance, beta-cell dysfunction, and hyperglucagonemia, the combination of which typically leads to hyperglycemia. Incretin-based treatment modalities, and in particular glucagon-like peptide 1 (GLP-1) receptor agonists, are able to successfully counteract several of the underlying pathophysiological abnormalities of T2DM. The pancreatic effects of GLP-1 receptor agonists include glucose-lowering effects by stimulating insulin secretion and inhibiting glucagon release in a strictly glucose-dependent manner, increased beta-cell proliferation, and decreased beta-cell apoptosis. GLP-1 receptors are widely expressed throughout human body; thus, GLP-1-based therapies exert pleiotropic and multisystemic effects that extend far beyond pancreatic islets. A large body of experimental and clinical data have suggested a considerable protective role of GLP-1 analogs in the cardiovascular system (decreased blood pressure, improved endothelial and myocardial function, functional recovery of failing and ischemic heart, arterial vasodilatation), kidneys (increased diuresis and natriuresis), gastrointestinal tract (delayed gastric emptying, reduced gastric acid secretion), and central nervous system (appetite suppression, neuroprotective properties). The pharmacologic use of GLP-1 receptor agonists has been shown to reduce bodyweight and systolic blood pressure, and significantly improve glycemic control and lipid profile. Interestingly, weight reduction induced by GLP-1 analogs reflects mainly loss of abdominal visceral fat. The critical issue of whether the emerging positive cardiometabolic effects of GLP-1 analogs can be translated into better clinical outcomes for diabetic patients in terms of long-term hard endpoints, such as cardiovascular morbidity and mortality, remains to be elucidated with prospective, large-scale clinical trials.