Papaetis Georgios S
Georgios S Papaetis, Internal Medicine and Diabetes Clinic, Paphos 8049, Cyprus.
World J Diabetes. 2014 Dec 15;5(6):817-34. doi: 10.4239/wjd.v5.i6.817.
The prevalence of type 2 diabetes (T2D) is evolving globally at an alarming rate. Prediabetes is an intermediate state of glucose metabolism that exists between normal glucose tolerance (NGT) and the clinical entity of T2D. Relentless β-cell decline and failure is responsible for the progression from NGT to prediabetes and eventually T2D. The huge burden resulting from the complications of T2D created the need of therapeutic strategies in an effort to prevent or delay its development. The beneficial effects of incretin-based therapies, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, on β-cell function in patients with T2D, together with their strictly glucose-depended mechanism of action, suggested their possible use in individuals with prediabetes when greater β-cell mass and function are preserved and the possibility of β-cell salvage is higher. The present paper summarizes the main molecular intracellular mechanisms through which GLP-1 exerts its activity on β-cells. It also explores the current evidence of incretin based therapies when administered in a prediabetic state, both in animal models and in humans. Finally it discusses the safety of incretin-based therapies as well as their possible role in order to delay or prevent T2D.
2型糖尿病（T2D）在全球范围内正以惊人的速度演变。糖尿病前期是葡萄糖代谢的一种中间状态，存在于正常糖耐量（NGT）和T2D临床实体之间。β细胞持续衰退和功能衰竭是导致从NGT进展为糖尿病前期并最终发展为T2D的原因。T2D并发症所带来的巨大负担促使人们需要采取治疗策略来预防或延缓其发展。基于肠促胰岛素疗法、二肽基肽酶-4抑制剂和胰高血糖素样肽-1（GLP-1）受体激动剂对T2D患者β细胞功能的有益作用，以及它们严格依赖葡萄糖的作用机制，表明在糖尿病前期个体中，当β细胞量和功能得以保留且β细胞挽救的可能性更高时，这些药物可能具有应用价值。本文总结了GLP-1对β细胞发挥作用的主要细胞内分子机制。还探讨了在糖尿病前期状态下给予基于肠促胰岛素疗法的现有证据，包括在动物模型和人类中的证据。最后讨论了基于肠促胰岛素疗法的安全性及其在延缓或预防T2D方面可能发挥的作用。
