Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
Department of Surgery, The University of British Columbia and Research Institute, BC Children's Hospital, Vancouver, Canada.
Diabetes Obes Metab. 2017 Sep;19(9):1205-1213. doi: 10.1111/dom.12935. Epub 2017 Jul 10.
Type 2 diabetes (T2D) is characterized by a gradual decline in pancreatic beta cell function that determines the progressive course of the disease. While beta-cell failure is an important contributor to hyperglycaemia, chronic hyperglycaemia itself is also detrimental for beta-cell function, probably by inducing prolonged secretory stress on the beta cell as well as through direct glucotoxic mechanisms that have not been fully defined. For years, research has been carried out in search of therapies targeting hyperglycaemia that preserve long-term beta-cell function in T2D, a quest that is still ongoing. Current strategies aim to improve glycaemic control, either by promoting endogenous insulin secretion, such as sulfonylureas, or by mechanisms that may impact the beta cell indirectly, for example, providing beta-cell rest through insulin treatment. Although overall long-term success is limited with currently available interventions, in this review we argue that strategies that induce beta-cell rest have considerable potential to preserve long-term beta-cell function. This is based on laboratory-based studies involving human islets as well as clinical studies employing intensive insulin therapy, thiazolidinediones, bariatric surgery, short-acting glucagon-like peptide (GLP)-1 receptor agonists and a promising new class of diabetes drugs, sodium-glucose-linked transporter (SGLT)-2 inhibitors. Nevertheless, a lack of long-term clinical studies that focus on beta-cell function for the newer glucose-lowering agents, as well as commonly used combination therapies, preclude a straightforward conclusion; this gap in our knowledge should be a focus of future studies.
2 型糖尿病（T2D）的特征是胰腺β细胞功能逐渐下降，这决定了疾病的进展过程。虽然β细胞衰竭是导致高血糖的重要因素，但慢性高血糖本身也不利于β细胞功能，可能通过对β细胞产生长期的分泌应激，以及通过尚未完全明确的直接糖毒性机制来实现。多年来，研究人员一直在寻找针对高血糖的治疗方法，以在 T2D 中保留长期的β细胞功能，这一探索仍在继续。目前的策略旨在改善血糖控制，方法是促进内源性胰岛素分泌，如磺酰脲类药物，或通过可能间接影响β细胞的机制，例如通过胰岛素治疗提供β细胞休息。尽管目前可用的干预措施总体上长期成功有限，但在这篇综述中，我们认为诱导β细胞休息的策略具有很大的潜力来保留长期的β细胞功能。这基于涉及人胰岛的实验室研究以及采用强化胰岛素治疗、噻唑烷二酮类药物、减肥手术、短效胰高血糖素样肽 (GLP)-1 受体激动剂和一类有前途的新型糖尿病药物——钠-葡萄糖协同转运蛋白 (SGLT)-2 抑制剂的临床研究。然而，由于缺乏针对新型降糖药物以及常用联合疗法的长期临床研究，无法得出明确的结论；我们对这些知识的缺乏应该成为未来研究的重点。
