Vagal Nerve Stimulation for Diabetes

糖尿病影响超过8%的美国人，在美国每年花费超过2450亿美元。虽然 有一些糖尿病患者对药物治疗无效或不能接受药物治疗， 由于体重增加和低血糖等副作用而接受药物治疗。 迷走神经刺激（VNS）已被应用或正在研究用于治疗癫痫，治疗- 由于其对自主神经功能的抑制或兴奋作用，抵抗抑郁、肥胖和心力衰竭。 在这个项目中，我们建议应用VNS治疗糖尿病，并且我们建议仅在糖尿病期间应用VNS。 餐后时期用于血糖控制的VNS的新概念是基于自主神经 不平衡在糖尿病中是常见的，并且VNS能够改善自主神经不平衡。低血糖 在我们的初步研究中，使用适当参数的VNS观察到了效果， 已显示增加胰高血糖素样肽-1和抑制血浆生长素释放肽。 本项目的具体目标是：1）推导出一种最有效的VNS降低血糖的方法， 通过系统地优化VNS参数、位置和持续时间的糖尿病犬模型; 2） 探讨优化的VNS对胃肠动力和激素的影响; 3）研究优化的VNS对胃肠动力和激素的影响。 迷走神经刺激对血糖控制的慢性作用及其安全性。CVRx的植入式脉冲发生器 将用于探索VNS对糖尿病的治疗潜力。 该项目的创新之处包括：1）VNS在糖尿病中的新应用; VNS已被应用于 治疗肥胖，但很少有糖尿病的报道。低频VNS将用于改善自主神经功能 失衡和胃肠动力障碍，因此降低血糖2）VNS将仅输送 3）通过改善自主神经功能来治疗肥胖的新概念 肠促胰岛素与VNS的关系是一个新的发现。 一个有竞争力的团队已经组建，包括神经调节，胃肠动力， 糖尿病临床管理、医疗器械和软件开发。

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.