Combining exercise with glucose lowering therapies for optimal metabolic health in type 2 diabetes

Aim
To undertake a programme of research investigating whether glucose lowering therapies work in synergy or interact with exercise training in the promotion of metabolic health.

Background
The vast majority of those with type 2 diabetes are prescribed glucose lowering therapies to help manage their condition, with many taking multiple types of therapies concurrently. Increased physical activity and exercise training are also promoted as important management interventions for type 2 diabetes. However, it is currently unknown whether glucose lowering therapies act to enhance or blunt responses to exercise. This is particular relevant to newer classes of diabetes medications, such as incretin-based therapies or sodium-glucose co-transporter-2 (SGLT2) inhibitors, which like exercise, act to promote weight management and improved cardiovascular health. Understanding how medications and exercise can be used together in the management of type 2 diabetes has important implications for personalised medicine and maximizing patient benefit.

Methods
The project will encompass a multi-disciplinary programme of research providing training and research activity across a range of different disinclines. Specifically the student will undertake an observational study followed by a series of experimental trials. The observational study will utilise large datasets with the aim of investigating whether different classes of glucose lowering therapies modify the association between physical activity and health outcomes. This will be followed by two focused experimental trials within a specialist exercise laboratory to test metabolic responses to exercise training in individuals with type 2 diabetes taking different glucose lowering therapies, with a specific focus on newer classes of medication. Exercise sessions will include treadmill and cycle ergometer based protocols. The first study will use a randomised acute design (response to a single bout of exercise) with the second study using a prospective 12 week design (responses to exercise training). Outcomes will include glucose (primary outcome), insulin and lipid responses to a mixed meal, continuous glucose monitoring and gold stand measures of body composition.

Timeline
Observational study: 0-18 months
Protocol development for intervention studies 1 & 2: 4-16 months
Ethics application preparation and submission for intervention studies 1 & 2: 6-18 months
Intervention studies completed: 24-34 months
Thesis write-up: 34 months onwards

Impact and outcomes
Exercise and pharmaceutical therapies are prescribed in isolation to each other in management of type 2 diabetes without knowing the extent of possible interactions or synergies that such combinations present. This programme of research will allow for more precision in understanding which glucose lowering therapies can be co-prescribed in a synergetic manor with exercise training and which therapies should be avoided.