SBIR-STTR Award

Diabetes affects more than 8% of Americans and costs over $174 billion in 2007 in USA. Recently bariatric surgery, such as Roux-en-Y gastric bypass, has been proposed for treating diabetic patients with obesity due to its hypoglycemic effect on postprandial blood glucose and significant weight loss. In this proposal, we propose a novel method of automated intestinal electrical stimulation (IES) for the treatment of diabetes. Based on previous published studies in our group, we have discovered that IES alters gastrointestinal motility, physiology and hormones in a way similar to the gastric bypass procedure: it reduces food intake and nutrient absorption, inhibits gastric ghrelin and increases glucagon-like peptide (GLP-1) in the postprandial state. Based on these findings, we hypothesize that acute IES improves postprandial hyperglycemia and chronic IES results in improvement in long-term glycemic control. If proven effective, the proposed IES has advantages of being adjustable, reversible and less invasive, compared with bariatric surgery. The Goto-Kakizaki (GK) rat, one of the best characterized animal models of spontaneous Type 2 diabetes and most widely used in studying anti-diabetic mechanisms of bariatric surgeries will be used in this project to prove following hypotheses and accomplish following specific aims. 1) To optimize IES methodology such that the hypoglycemic effect of IES is maximized. Particularly, the stimulation parameters of IES will be systematically investigated and optimized. The effects of acute optimized IES on postprandial blood glucose and insulin sensitivity will be carefully examined. 2) To investigate possible mechanisms involved in the hypoglycemic effect of acute IES. Experiments are designed to test the hypothesis that IES-induced reduction in postprandial blood glucose is mediated mechanically by delayed gastric emptying and accelerated intestinal transit, and hormonally by reduced ghrelin and increased release of GLP-1. 3) To study effects and mechanisms of chronic IES on long-term glycemic control. Chronic experiments are designed to test the hypothesis that improvement in postprandial hyperglycemia prevents/reduces the detrimental effect of chronic hyperglycemia on beta-cell function and systemic insulin sensitivity, leading to improvement of long-term glucose control. An automatic food intake detection algorithm will be developed for the chronic experiments. A multi-disciplinary team has been assembled to undertake the task. The PI has extensive experience in gastrointestinal electrical stimulation on gastrointestinal motility, obesity and diabetes. The consultant Dr. Abate is an expert from in insulin resistance and diabetes. The small business has all required expertise and facilities to design and develop the proposed automatic feedback controlled IES system.

Public Health Relevance Statement:


Public Health Relevance:
Diabetes affects more than 8% of Americans. A novel method of weak electrical stimulation in the small intestine is proposed for treating diabetes.

NIH Spending Category:
Diabetes; Digestive Diseases; Nutrition; Obesity; Prevention

Project Terms:
Abate; absorption; Acceleration; Acute; Affect; Algorithms; American; Animal Model; Animals; bariatric surgery; base; Beta Cell; Blood Glucose; blood glucose regulation; Body Weight; Body Weight decreased; Businesses; Bypass; Cell physiology; Characteristics; Chronic; Controlled Study; cost; design; Detection; Development; Diabetes Mellitus; diabetic; diabetic patient; diabetic rat; Disease; Disease remission; Distal; Down-Regulation; Duodenum; Eating; Electric Stimulation; Electrodes; Exclusion; experience; Feedback; Gastric Bypass; Gastric Emptying; gastrointestinal; Gastrointestinal Motility; Gastroparesis; ghrelin; glucagon-like peptide; Glucose; glycemic control; Goals; Heart Diseases; Hormones; Human; Hyperglycemia; Hypoglycemia; improved; Insulin Resistance; insulin sensitivity; Intestinal Absorption; Intestines; jejunum; Kidney Failure; Mediating; Medical; Methodology; Methods; Non-Insulin-Dependent Diabetes Mellitus; novel; Nutrient; Obesity; Oral; Patients; Phase; Physiology; prevent; Procedures; public health relevance; Publishing; Rattus; research study; Safety; Series; Small Intestines; Stomach; Stroke; System; Testing; Work

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 ? 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.

Public Health Relevance Statement:
Diabetes is an epidemic health problem in the USA and around the world. In this project, a novel method of treatment is proposed by delivering weak electrical current to the small intestine to reduce blood glucose.

NIH Spending Category:
Diabetes; Digestive Diseases; Nutrition; Obesity

Project Terms:
absorption; Affect; Algorithms; American; Amplifiers; Animals; bariatric surgery; base; Beta Cell; Blood Glucose; blood glucose regulation; Catheters; Cell physiology; Charge; Chronic; Computer software; Controlled Study; cost; Data; design; Detection; Development; Device or Instrument Development; Diabetes Mellitus; diabetes mellitus therapy; diabetic patient; digital; Duodenum; Eating; Electric Stimulation; Electric Stimulation Therapy; Electrocardiogram; Electrodes; Epidemic; Event; Fasting; feeding; Food; Frequencies; Future; Gastric Bypass; Gastrointestinal Hormones; glucagon-like peptide 1; Goals; Health; heart rate variability; Hour; Human; Hyperglycemia; Hypoglycemia; implantation; Ingestion; innovation; Intestines; Medical; Medical Device; Memory; Methods; Morbid Obesity; neuroregulation; Non-Insulin-Dependent Diabetes Mellitus; Nose; novel; Nutrient; nutrient absorption; Obesity; Operative Surgical Procedures; Outcome; patient response; patient screening; Patients; Phase; Physiologic pulse; Physiological; prevent; Procedures; Process; reduced food intake; Research; response; Rodent Model; safety study; sensor; Serous Membrane; side effect; Signal Transduction; Small Intestines; Smooth Muscle; Specific qualifier value; statistics; Stimulus; Stomach; subcutaneous; System; Telemetry; Testing; Time; Training; Weight Gain; Width; Work