Vagal Nerve Stimulation for Diabetes

迷走神经刺激治疗糖尿病

• 批准号: 9268933
• 负责人: Jieyun None Yin
• 金额: $ 47.41万
• 依托单位: TRANSTIMULATION RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-20 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9268933
• 关键词: Acute; Adverse effects; Affect; Aftercare; American; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Blood Glucose; Blood specimen; Body Weight; Canis familiaris; Cervical; Chronic; Clinical Management; Clinical Research; Data; Device or Instrument Development; Devices; Diabetes Mellitus; Eating; Ensure; Epilepsy; FDA approved; Fasting; Frequencies; Gastric Bypass; Gastrointestinal Hormones; Gastrointestinal Motility; Glucose; Health; Heart failure; Hormones; Hypoglycemia; Inflammatory Bowel Diseases; Insulin; Insulin Resistance; Intestinal Absorption; Intestines; Investigation; Location; Measures; Medical; Medical Device; Mental Depression; Metabolic syndrome; Methodology; Methods; Modeling; Motor; Nerve; Non-Insulin-Dependent Diabetes Mellitus; Norepinephrine; OGTT; Obesity; Operative Surgical Procedures; Pancreatic Polypeptide; Pathway interactions; Patients; Physiologic pulse; Plasma; Postprandial Period; Procedures; Rattus; Refractory; Reporting; Resistance; Rodent; Safety; Series; Stomach; Tachyphylaxis; Testing; Therapeutic; Time; Vagus nerve structure; Weight Gain; Width; Work; absorption; bariatric surgery; base; cholinergic; cost; design; diabetic; diabetic patient; feeding; gastric inhibitory polypeptide receptor; gastrointestinal; ghrelin; glucagon-like peptide; glycemic control; heart rate variability; improved; incretin hormone; insulin secretion; insulin tolerance; motility disorder; neuroregulation; novel; nutrient absorption; nutrient metabolism; prevent; reduced food intake; research study; sham surgery; software development; standard of care

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.

在美国，糖尿病影响超过8％的美国人，每年成本超过2450亿美元。虽然 可以使用医疗疗法，有糖尿病患者对医疗疗法难治性或不能 由于体重增加和低血糖等副作用，因此受到医学治疗。 迷走神经刺激（VNS）已应用或正在研究以治疗癫痫，治疗 - 耐药性抑郁，肥胖和心力衰竭是由于其对自主功能的抑制作用或兴奋性影响。 在这个项目中，我们建议应用VNS治疗糖尿病，进一步提议仅在此期间应用VNS 餐后期。血糖控制的VN的新颖概念是基于自主神经的事实 失衡在糖尿病中很常见，VNS能够改善自主性失衡。降血糖 在我们的初步研究中，已经使用适当参数的VN观察到效果 被证明会增加胰高血糖素样肽-1并抑制血浆生长素素。 该项目的具体目的是1）得出一种最有效的VN方法来减少血糖 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）到 研究优化VNS对胃肠道运动和激素的影响； 3）调查 VNS对血糖控制及其安全性的慢性影响。 CVRX的植入脉冲发生器 将用于探索VNS对糖尿病的治疗潜力。 该项目的新颖性包括：1）VNS在糖尿病中的新应用； VNS已应用 治疗肥胖，但据报道糖尿病几乎没有报道。低频VN将用于改善自主神经 因此，不平衡和胃肠道不平衡性障碍降低血糖2）仅将VN递送 在食物摄入期间，可以防止速度刺激； 3）通过提高自主神经来治疗肥胖的新颖概念 功能； 4）泌乳素激素与VNS的参与是新的。 一支竞争激烈的团队已组装，包括神经调节，胃肠道运动的专业知识， 糖尿病，医疗设备和软件开发的临床管理。