Vagal Nerve Stimulation for Diabetes

糖尿病影响了超过8%的美国人，在美国每年的成本超过2450亿美元。虽然 有可用的医疗方法，有糖尿病患者对药物治疗无效或不能 因体重增加和低血糖等副作用而接受医学治疗。 迷走神经刺激(VNS)已应用于或正在研究中，用于治疗癫痫，治疗- 抵抗抑郁、肥胖和心力衰竭，因为它对自主神经功能有抑制或兴奋作用。 在这个项目中，我们建议将VNS应用于糖尿病的治疗，并进一步建议仅在 餐后时期。用于血糖控制的VNS的新概念是基于这样一个事实：自主神经 失衡在糖尿病中很常见，VNS能够改善自主神经失衡。一种降血糖药 在我们的初步研究中，我们观察到了适当参数的VNS的效果，并且进一步的VNS已经 已被证明可以增加胰升糖素样肽-1和抑制血浆Ghrelin。 本项目的具体目标是：1)寻找一种最有效的迷走神经降低血糖的方法 通过系统优化VNS参数、位置和持续时间建立糖尿病犬模型；2) 研究优化后的VNS对胃肠动力和激素的影响；3)研究 VNS对血糖控制的慢性影响及其安全性。CVRx植入式脉冲发生器 将用于探索VNS对糖尿病的治疗潜力。 本项目的新颖性包括：1)VNS在糖尿病治疗中的新应用；VNS已应用于 治疗肥胖症，但很少有糖尿病的报道。将使用低频VNS来改善自主神经 不平衡和胃肠动力障碍因此降低血糖2)VNS将只提供 3)通过改善自主神经来治疗肥胖的新概念 4)肠促性素激素参与VNS的研究是一个新的课题。 已经组建了一支有竞争力的团队，成员包括神经调节、胃肠动力、 糖尿病临床管理、医疗器械及软件开发。

Diabetes affects more than 8% of Americans with an annual cost of over $245 billion in USA. Although medical therapies are available, there are diabetic patients who are refractory to medical therapies or cannot be treated medically due to side effects such as weight gain and hypoglycemia. Vagal nerve stimulation (VNS) has been applied or under investigation for treating epilepsy, therapy- resistance depression, obesity and heart failure due to its inhibitory or excitatory effect on autonomic functions. In this project, we propose to apply VNS to treat diabetes and further we propose to apply VNS only during the postprandial periods. The novel concept of VNS for glycemic control is based on the facts that autonomic imbalance is common in diabetes and VNS is capable of improving autonomic imbalance. A hypoglycemic effect has been observed with VNS of appropriate parameters in our preliminary studies and further VNS has been shown to increase glucagon-like peptide-1 and inhibit plasma ghrelin. The specific aims of this project are 1) to derive a most effective method of VNS in reducing blood glucose in a canine model of diabetes by systematically optimizing VNS parameters, location and duration; 2) to investigate the effects of the optimized VNS on gastrointestinal motility and hormones; 3) to investigate the chronic effects of VNS on glycemic control and its safety profile. The implantable pulse generator from CVRx will be used to explore the therapeutic potential of VNS for diabetes. The novelties of this project include: 1) a novel application of VNS for diabetes; VNS has been applied for treating obesity but little was reported for diabetes. Low frequency VNS will be used for improving autonomic imbalance and gastrointestinal dysmotility therefore reducing blood glucose 2) VNS will be delivered only during food intake which prevents tachyphylaxis; 3) a novel concept of treating obesity by improving autonomic functions; 4) The involvement of incretin hormones with VNS is new. A competitive team has been assembled to include expertise in neuromodulation, gastrointestinal motility, clinical management on diabetes, medical device and software development.