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

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509486/1 30/09/2016 30/03/2022
2029368 Studentship EP/N509486/1 01/11/2017 29/04/2021 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 09/2017 
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.