The influence of vestibular stimulation on metabolism and body composition

Abstract

Background: The metabolic diseases of obesity and type 2 diabetes (T2DM) represent a rapidly increasing and very serious public health challenge across the globe. Although previously seen as a ‘Western’ issue, the effects are now becoming more evident throughout the developing world with ~2 billion people classified as overweight. Whilst it is well known that lifestyle factors, such as physical activity and caloric intake influence adipose storage and glucose metabolism, emerging evidence suggests that autonomic regulation of metabolism is managed within the homeostatic nuclei of the hypothalamus and brainstem. As a consequence of these detrimental lifestyle changes, even within a relatively modest period, increased blood glucose, leptin and circulating fatty acid levels may cause desensitisation and inflammatory damage to neurones in these regions, leading to altered neuro-endocrine regulation, glucose utilization, fat storage, appetite, and satiety, promoting disruption of metabolic homeostasis, obesity and T2DM. Therefore, development of medical interventions that specifically influence these key nuclei may hold therapeutic potential as a novel treatment for these conditions. In this regard, growing evidence indicates that electrical stimulation of the vestibular system influences the brainstem and hypothalamus to improve metabolism and reduce fat storage, in a safe and easy to deliver manner via non-invasive electrode pads placed on the mastoids. The aim of this thesis was to develop and assess the therapeutic potential of non-invasive electrical vestibular stimulation as a novel approach to improve body composition and metabolic function in overweight and T2DM adults.

Methods: A literature review was carried out to assess current understanding and therapeutic approaches to obesity and T2DM, together with knowledge of interactions between these disease processes and the specific role of the vestibular system. In addition, the history, clinical outcomes, and technical requirements of electrical vestibular stimulation were reviewed as the basis for the series of three complementary clinical studies described in this thesis. An initial study was carried out in collaboration with The Clinical Research Centre, University College Dublin, assessing clinical and safety outcomes in a population of adults who were either overweight or obese over 12 weeks, It and designed to investigate potential benefit of adding repeated electrical vestibular stimulation as an adjunctive therapy to a traditional weight loss approach. A second study was carried out at University College Dublin to assess potential benefit of repeated electrical vestibular stimulation, as measured by reduction in HbA1c, in a population of T2DM adults over a period of 16 weeks. Finally, a third study was completed in collaboration the Vestibular Research Lab, Vishnu Dental College, India to assess potential benefit of electrical vestibular stimulation in an Indian adult T2DM population.

Results: All three studies have provided valuable insights into how repeated electrical stimulation may impact the metabolic diseases of obesity and T2DM. Specifically, in terms of the primary endpoint, study one demonstrated reductions in body weight, with studies two and three both reporting decreased circulating glucose levels. Furthermore, improvements in blood pressure (studies one, two and three) and blood lipids (studies two and three), two important cardiometabolic markers, where also noted. Together, the results from these complementary clinical studies have provided compelling evidence to support the theory that non-invasive electrical stimulation of the vestibular system positively influences both energy regulation and body composition; when delivered in the setting of metabolic disease this approach appears to generate improvements in body weight and blood glucose. In terms of overall metabolic health, the reported reductions in blood pressure and improvements in lipid profile add credibility to this theory and further suggest that electrical vestibular stimulation reduces overall cardiovascular risk. In parallel, blinding assessments conducted during the trials suggested a high degree of success with both the active and sham devices, whilst follow-up safety analysis of long-term usage of the active device usage highlighted that the technology is both safe and well tolerated.

Conclusion: The research presented in this thesis has provided new scientific knowledge in the fields of metabolic medicine, vestibular neurology, and neuromodulation medical device technology. The generated outcomes are significant and further complement the strong body of previously published literature in demonstrating important vestibular integrations into the homeostatic sites of the brainstem and hypothalamus which may be modulated to influence metabolism. Specifically, this research has shown that repeated electrical stimulation of the vestibular system, when delivered to adults via a wearable neuromodulation device, can contribute to improved metabolic health outcomes such as reduced body weight, reduced cholesterol and reduced HbA1c. Given that this non-invasive technology is safe, low-cost, and easy to use, it may provide a novel opportunity for the treatment of T2DM and metabolic disease.

Thesis is embargoed until 31 July 2025.

Date of Award	Jul 2023
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Neurovalens Ltd
Supervisor	Paul McGeoch (Supervisor) & David Grieve (Supervisor)