Automated Intestinal Electrical Stimulation for Diabetes

糖尿病影响超过9%的美国人，2017年在美国花费超过3000亿美元。药物治疗在治疗肥胖的糖尿病患者方面具有局限性，这是由于其常见的体重增加的副作用。减肥手术已被提出用于治疗糖尿病患者，具有良好的效果。在这个项目中，我们提出了一种新的方法，肠电刺激（IES）治疗糖尿病。在生理学上，已证明拟定IES的作用类似于减肥手术，包括减少吸收和食物摄入，以及增强胰高血糖素样肽-1（GLP-1）的分泌。我们的I期项目的完成和其他最近的研究已经证明了所提出的IES的有希望的降血糖作用以及涉及胃肠道激素和β细胞功能的机制。这些发现使我们相信IES是糖尿病的可行疗法。因此，我们建议在这个项目中设计和开发一个新的IES系统。该项目的目的是开发一种创新的植入式脉冲发生器（IPG）和一种用于筛查患者的特殊肠道导管。拟议的系统将如下工作：一旦确定潜在的糖尿病患者，将使用腔内导管对他或她进行非手术筛查，以确定反应性。如果测试表明对IES的反应良好，则将通过腹腔镜放置永久性IPG。IES将在进食后几小时内自动输送。为了达到最大的功效，每个电刺激将在检测到固有的小肠肌电波时传递，这种方法称为同步IES。将设计和开发一种具有两个特殊功能的IPG，一个是自动检测食物摄入，另一个是检测固有肠肌电活动的峰值以实现同步。这些嵌入式算法，按需闭环IES是可行的。第二，设计并研制一种特殊的腔内导管。它可用于执行IES而无需任何外科手术，并筛选患者进行永久IES治疗。PI组建了一个全面而有竞争力的团队，拥有神经调节、糖尿病研究、医疗器械开发和软件实施方面的专业知识。

Diabetes affects more than 9% of Americans and costs over $300 billion in 2017 in USA. Medical therapies have limitations in treating diabetic patients with obesity due their common side effects of weight gain. Bariatric surgery has been proposed for treating diabetic patients with promising outcomes. In this project, we propose a novel method of intestinal electrical stimulation (IES) for treating diabetes. Physiologically, the effects of the proposed IES have been shown to be resemble to bariatric surgery, including reduction in absorption and food intake, and enhanced secretion of glucagon like peptide-1 (GLP-1). The completion of our Phase I project and other recent studies has demonstrated promising hypoglycemic effects of the proposed IES and mechanisms involving gastrointestinal hormones and β cell functions. These findings have led us to believe that IES is a viable therapy for diabetes. Accordingly, we propose to design and develop a novel IES system in this project. The aim of this project is to develop an innovative implantable pulse generator (IPG) and a special intestinal catheter to be used for screening patients. The proposed system will work as follows: once a potential patient with diabetes is identified, he or she will be screened non-surgically using an intraluminal catheter to determine the responsiveness. If the test indicates a good response to IES, a permanent IPG will be placed laparoscopically. The IES will be delivered automatically upon food intake for a few hrs. To achieve maximum efficacy, each electrical stimulus will be delivered upon the detection of an intrinsic small intestinal myoelectrical wave, a method called synchronized IES. An IPG incorporated with two special features will be designed and developed, one to automatically detect food intake and the other to detect peak of intrinsic intestinal myoelectrical activity for synchronization. With these imbedded algorithms, on-demand closed-loop IES is made feasible. Secondly, a special intraluminal catheter will be designed and developed. It can be used to perform IES without any surgical procedures and screen patients for permanent IES therapy. The PI has assembled a comprehensive and competitive team with expertise in neuromodulation, diabetes research, medical device development and software implementation.