Neuro Modulated Diabetes Control (NeuMeDic): Decoding the brain and neural pathways to achieve a better control of diabetes
Lead Research Organisation:
Imperial College London
Department Name: Electrical and Electronic Engineering
Abstract
Diabetes is a disease caused by a breakdown in the glucose metabolic process resulting in abnormal blood glucose fluctuations. Traditionally, control has involved external insulin injection in response to elevated blood glucose to substitute the role of the beta cells in the pancreas, which would otherwise perform this function in a healthy individual.
The central nervous system (CNS), however, also plays a vital role in glucose homoeostasis through the control of pancreatic secretion and insulin sensitivity which could potentially be used as a pathway for enhancing glucose control. Within this context, a novel emerging field called bioelectronic medicine, which relies on electrical modulation of the neural signals to the organs, has been introduced as an alternative treatment to using pharmaceuticals. Furthering this new emerging field, this PhD project aims at studying whether there is potential benefit of interfacing with the neural pathways through bioelectronic medicine for acquiring a tighter control of glucose levels in people with diabetes.
In more detail, this PhD project aims at: i) understanding the physiological basis that underlie this neural regulation in the healthy and diabetic states in vivo (particularly during meals), ii) studying for the first time the potential benefits of modulating these neural signals in vivo for diabetes management and iii) developing novel mathematical models to be included in existing healthy and diabetes simulators. This new approach for diabetes management will have a great impact on the diabetic patients' quality of life. It will allow diabetic people to automatically maintain a better glucose control, leading to a reduction of the complications derived from its deregulation. It will also impact health care services by reducing the medical costs associated with this disease ($245 billion in US in 2012).
Therefore, the proposed PhD will lead to major scientific contributions in the fields of Neurotechnology and Diabetes. This PhD is in alignment with several EPSRC research areas, including Mathematical Biology and Engineering Design.
The central nervous system (CNS), however, also plays a vital role in glucose homoeostasis through the control of pancreatic secretion and insulin sensitivity which could potentially be used as a pathway for enhancing glucose control. Within this context, a novel emerging field called bioelectronic medicine, which relies on electrical modulation of the neural signals to the organs, has been introduced as an alternative treatment to using pharmaceuticals. Furthering this new emerging field, this PhD project aims at studying whether there is potential benefit of interfacing with the neural pathways through bioelectronic medicine for acquiring a tighter control of glucose levels in people with diabetes.
In more detail, this PhD project aims at: i) understanding the physiological basis that underlie this neural regulation in the healthy and diabetic states in vivo (particularly during meals), ii) studying for the first time the potential benefits of modulating these neural signals in vivo for diabetes management and iii) developing novel mathematical models to be included in existing healthy and diabetes simulators. This new approach for diabetes management will have a great impact on the diabetic patients' quality of life. It will allow diabetic people to automatically maintain a better glucose control, leading to a reduction of the complications derived from its deregulation. It will also impact health care services by reducing the medical costs associated with this disease ($245 billion in US in 2012).
Therefore, the proposed PhD will lead to major scientific contributions in the fields of Neurotechnology and Diabetes. This PhD is in alignment with several EPSRC research areas, including Mathematical Biology and Engineering Design.
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509486/1 | 01/10/2016 | 31/03/2022 | |||
| 2029368 | Studentship | EP/N509486/1 | 01/11/2017 | 30/04/2021 | Amparo Guemes Gonzalez |
| Description | Following a scienti?c-based approach, the work funded through this award allowed to carry out studies that increased our understanding of the physiological mechanisms underlying the neural glycemic regulation. To begin with, in vivo experiments in rodents provided new insights into the impact of vagus nerve stimulation (VNS) frequency on blood glucose, insulin and glucagon concentrations. We demonstrated that the higher the stimulation frequency, the greater and more consistent change in glucose levels. To further characterize this neuro-metabolic interaction, we develop and validated the ?rst mathematical model describing the physiological metabolic events after cervical VNS. Then, using an application-based strategy, our work investigated the opportunities for incorporating bioelectronic medicine to traditional diabetes technology in clinical scenarios. In particular, in one study we presented the proof of concept of a novel closed-loop glucose controller that regulates the insulin and glucagon dose delivery, and drive the insulin sensitivity (SI) of virtual patients using neuromodulation. Our in silico experiments demonstrated improved safety and e?cacy compared to traditional controllers. Finally, in an additional study, we introduced an original data-driven approach to predict the quality of overnight glycaemia based on the application of binary classi?ers on metabolic data. The proposed approach was able to predict whether overnight glucose concentrations are going to remain within or outside the target range, and therefore allows the user to take appropriate preventive actions (e.g. snack or change in basal insulin). |
| Exploitation Route | It is well established that the nervous system has a significant role in keeping tight control of blood glucose oscillations, in healthy and disease conditions. The ultimate aim of this project is to integrate the acquired knowledge about the neural mechanisms of glucose control and the impact of neural stimulation into current techniques for the management of diabetes. Our approach is to develop novel neuromodulation-pharmaceutical therapeutic technology for people with diabetes that overcomes the limitations of traditional pharmaceutical approaches. These results will definitely strengthen the multidisciplinary scientific-technical knowledge in bioelectronic medicine and diabetes and present preclinical evidence of new technological solutions that can provide improved outcomes. The application of the novel ICT tools and techniques developed in this work could be extended to other disciplines that interface with the nervous system, such as in emerging therapies for other chronic diseases like autoimmune diseases. |
| Sectors | Electronics,Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | Rafael del Pino Excellence Scholarships |
| Amount | € 50,000 (EUR) |
| Organisation | Rafael del Pino Foundation |
| Sector | Charity/Non Profit |
| Country | Spain |
| Start | 10/2017 |
| End | 09/2019 |
| Description | NeuMeDiC - JHU |
| Organisation | Johns Hopkins University |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Work on instrumentation, biosensors, neural signal processing and in vivo validation of models and control algorithms. I also perform the surgeries for the in vivo experiments when the primary surgeon is not available. |
| Collaborator Contribution | Prof. Etienne-Cummings' time. This will support his time as Principal Investigator (Project Director) over the year duration of this project. His expertise is applied to instrumentation development to collect signals from, and to apply signals to the vagus nerve. Co-Director, Integrated Physiology Core of Diabetes Research Center and Associate Professor of Psychiatry and Behavioral Sciences, Dr. Sheng Bi, is an expert on diabetes research. The overall goal of his research projects is to elucidate the neural mechanisms underlying the controls of food intake and energy expenditure and in the regulation of glucose homeostasis. His contribution will be using in vivo animal models to validate the models of glucose control that are developing. A veterinary or surgeon will be responsible for the neurosurgical and neurophysiological in vivo experiments in rat models. |
| Impact | Awarded a 2019 Johns Hopkins Discovery Award to multidisciplinary research merging engineering (electronics, signal processing, sensors) and medicine (in vivo experiments on rat models). This collaboration aim at giving insight into the dynamics of insulin and glucagon secretion, and therefore, glucose regulation after electrical stimulation of the vagus nerve. To date, a pilot study investigating the metabolic and hemodynamic impact on healthy animals of two stimulation con?gurations has been performed. Two stimulation frequencies of 5Hz and 10Hz, with otherwise same con?guration parameters (monopolar, biphasic charge-balanced square pulses, 1.75mA pulse amplitude, 0.5ms pulse width) were applied to the intact left cervical vagus nerve in fasted anesthetized healthy rats for combined a?erent and e?erent VNS. It was demonstrated that stimulation on the intact nerve consistently resulted in an immediate and sustained increase in glucose concentration using either frequency, with the highest frequency having the greatest percentage of change over baseline. No responses were obtained in insulin or glucagon levels, suggesting that glucose-regulatory mechanisms independent from the pancreatic hormonal secretion are involved. Further contributions may arise from the experimental studies that are currently ongoing. |
| Start Year | 2019 |
| Title | ARTIFICIAL PANCREAS WITH NEURAL SIGNAL INPUT |
| Description | There is provided apparatus for controlling the delivery of insulin to a subject. The apparatus comprises a first input (18) for receiving neural information from the subject indicative of prospective or actual food and/or drink intake and a second input (15) for receiving a signal indicative of the subject's blood glucose level (BG). The apparatus further comprises a processor or processors (10) configured to determine food and/or drink characteristics based on the received neural information and to determine an amount of insulin to be delivered based on the measured blood glucose levels (BG) and the determined food and/or drink characteristics, and an output for providing an insulin pump control signal (12) indicative of the determined amount of insulin. |
| IP Reference | WO2019207007 |
| Protection | Patent application published |
| Year Protection Granted | 2019 |
| Licensed | No |
| Impact | Not applicable for the moment. |