Groeneveld Onno N, Kappelle L Jaap, Biessels Geert Jan
University Medical Center Utrecht Brain Center Rudolf Magnus Department of Neurology Utrecht the Netherlands.
J Diabetes Investig. 2016 Jan;7(1):5-16. doi: 10.1111/jdi.12420. Epub 2015 Oct 3.
Patients with type 2 diabetes mellitus are at risk for accelerated cognitive decline and dementia. Furthermore, their risk of stroke is increased and their outcome after stroke is worse than in those without diabetes. Incretin-based therapies are a class of antidiabetic agents that are of interest in relation to these cerebral complications of diabetes. Two classes of incretin-based therapies are currently available: the glucagon-like-peptide-1 agonists and the dipeptidyl peptidase-4 -inhibitors. Independent of their glucose-lowering effects, incretin-based therapies might also have direct or indirect beneficial effects on the brain. In the present review, we discuss the potential of incretin-based therapies in relation to dementia, in particular Alzheimer's disease, and stroke in patients with type 2 diabetes. Experimental studies on Alzheimer's disease have found beneficial effects of incretin-based therapies on cognition, synaptic plasticity and metabolism of amyloid-β and microtubule-associated protein tau. Preclinical studies on incretin-based therapies in stroke have shown an improved functional outcome, a reduction of infarct volume as well as neuroprotective and neurotrophic properties. Both with regard to the treatment of Alzheimer's disease, and with regard to prevention and treatment of stroke, randomized controlled trials in patients with or without diabetes are underway. In conclusion, experimental studies show promising results of incretin-based therapies at improving the outcome of Alzheimer's disease and stroke through glucose-independent pleiotropic effects on the brain. If these findings would indeed be confirmed in large clinical randomized controlled trials, this would have substantial impact.
2型糖尿病患者有认知能力加速衰退和患痴呆症的风险。此外，他们中风的风险增加，且中风后的预后比非糖尿病患者更差。基于肠促胰岛素的疗法是一类抗糖尿病药物，与糖尿病的这些脑部并发症相关。目前有两类基于肠促胰岛素的疗法：胰高血糖素样肽-1激动剂和二肽基肽酶-4抑制剂。基于肠促胰岛素的疗法除了具有降糖作用外，可能还对大脑有直接或间接的有益影响。在本综述中，我们讨论基于肠促胰岛素的疗法在2型糖尿病患者痴呆症（尤其是阿尔茨海默病）和中风方面的潜力。关于阿尔茨海默病的实验研究发现，基于肠促胰岛素的疗法对认知、突触可塑性以及淀粉样蛋白-β和微管相关蛋白tau的代谢有有益影响。关于基于肠促胰岛素的疗法在中风方面的临床前研究表明，其功能预后得到改善、梗死体积减小，以及具有神经保护和神经营养特性。无论是在阿尔茨海默病的治疗方面，还是在中风的预防和治疗方面，针对有或没有糖尿病的患者的随机对照试验正在进行。总之，实验研究表明，基于肠促胰岛素的疗法通过对大脑的非依赖葡萄糖的多效性作用来改善阿尔茨海默病和中风的预后，结果很有前景。如果这些发现确实能在大型临床随机对照试验中得到证实，将会产生重大影响。
