Automated Intestinal Electrical Stimulation for Diabetes

糖尿病影响了超过9%的美国人，2017年美国的糖尿病成本超过3000亿美元。由于糖尿病患者体重增加的常见副作用，治疗肥胖的糖尿病患者的药物治疗有局限性。减肥手术已被提议用于治疗糖尿病患者，结果令人振奋。在这个项目中，我们提出了一种新的肠道电刺激(IES)治疗糖尿病的方法。从生理上讲，拟议的IES的效果已被证明类似于减肥手术，包括减少吸收和食物摄取，以及增加胰升糖素样肽-1(GLP-1)的分泌。我们第一阶段项目的完成和其他最近的研究表明，拟议的IES具有良好的降血糖作用，并涉及胃肠激素和β细胞功能的机制。这些发现使我们相信IES是一种可行的糖尿病治疗方法。因此，我们提出了在本项目中设计和开发一种新型的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)和一种特殊的肠道导管，用于筛查患者。拟议的系统将如下工作：一旦确定了潜在的糖尿病患者，他或她将使用腔内导管进行非手术筛查，以确定反应。如果测试显示对IES反应良好，将在腹腔镜下放置永久性IPG。IES将在食物摄入后几个小时内自动交付。为了达到最大的疗效，每个电刺激都将在检测到固有的小肠肌电波时传递，这种方法被称为同步IES。将设计和开发一种集成了两个特殊功能的IPG，一个用于自动检测食物摄入量，另一个用于检测固有肠道肌电活动的峰值以进行同步。通过这些嵌入的算法，使得按需控制的闭环IES成为可能。其次，将设计和开发一种特殊的腔内导管。它可用于实施IES而无需任何外科手术，并可用于筛选接受永久性IES治疗的患者。PI组建了一支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.