Remission of type 2 diabetes and improved diastolic function by combining structured exercise with meal replacement and food reintroduction among young adults: the RESET for REMISSION randomised controlled trial protocol
Melanie J Davies,
Thomas Yates,
Elham Rahme,
Gerry P McCann,
Joseph Henson,
Kaberi Dasgupta,
Deborah Chan,
Isabel Fortier,
Deborah Da Costa,
Edward Gregg,
Stéphanie Chevalier,
Matthew McCarthy,
Mark Sherman,
Emma Redman,
Matthias G Friedrich,
Carla M Prado,
Richard B Thompson,
Michelle Hadjiconstantinou,
Abhishek Dattani,
Normand Boulé,
Julia Champagne,
Frank Arsenyadis,
Jordan Rees,
Roseanne Yeung
Affiliations
Melanie J Davies
Diabetes Research Centre, University of Leicester and NIHR Leicester Biomedical Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
Thomas Yates
Diabetes Research Centre, University of Leicester and NIHR Leicester Biomedical Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
Elham Rahme
Department of Medicine, McGill University and Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
Gerry P McCann
Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Biomedical Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
Joseph Henson
Diabetes Research Centre, University of Leicester and NIHR Leicester Biomedical Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
Kaberi Dasgupta
Department of Medicine, McGill University and Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
Deborah Chan
Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
Isabel Fortier
Department of Medicine, McGill University and Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
Deborah Da Costa
Department of Medicine, McGill University and Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
Edward Gregg
School of Public Health, Imperial College London, London, UK
Stéphanie Chevalier
School of Human Nutrition, McGill University, Montreal, Quebec, Canada
Matthew McCarthy
Diabetes Research Centre, University of Leicester and NIHR Leicester Biomedical Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
Mark Sherman
Department of Medicine, McGill University, Montreal, Quebec, Canada
Emma Redman
Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust and NIHR Leicester Biomedical Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
Matthias G Friedrich
Courtois Cardiovascular Signature Centre, McGill University Health Centre and Departments of Medicine and Diagnostic Radiology, McGill University, Montreal, Quebec, Canada
Carla M Prado
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
Richard B Thompson
Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada
Michelle Hadjiconstantinou
Diabetes Research Centre, University of Leicester and NIHR Leicester Biomedical Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
Abhishek Dattani
Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Biomedical Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
Normand Boulé
Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
Julia Champagne
Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
Frank Arsenyadis
Diabetes Research Centre, University of Leicester and NIHR Leicester Biomedical Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
Jordan Rees
Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
Roseanne Yeung
Division of Endocrinology & Metabolism, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
Introduction Type 2 diabetes mellitus (T2DM) onset before 40 years of age has a magnified lifetime risk of cardiovascular disease. Diastolic dysfunction is its earliest cardiac manifestation. Low energy diets incorporating meal replacement products can induce diabetes remission, but do not lead to improved diastolic function, unlike supervised exercise interventions. We are examining the impact of a combined low energy diet and supervised exercise intervention on T2DM remission, with peak early diastolic strain rate, a sensitive MRI-based measure, as a key secondary outcome.Methods and analysis This prospective, randomised, two-arm, open-label, blinded-endpoint efficacy trial is being conducted in Montreal, Edmonton and Leicester. We are enrolling 100 persons 18–45 years of age within 6 years’ T2DM diagnosis, not on insulin therapy, and with obesity. During the intensive phase (12 weeks), active intervention participants adopt an 800–900 kcal/day low energy diet combining meal replacement products with some food, and receive supervised exercise training (aerobic and resistance), three times weekly. The maintenance phase (12 weeks) focuses on sustaining any weight loss and exercise practices achieved during the intensive phase; products and exercise supervision are tapered but reinstituted, as applicable, with weight regain and/or exercise reduction. The control arm receives standard care. The primary outcome is T2DM remission, (haemoglobin A1c of less than 6.5% at 24 weeks, without use of glucose-lowering medications during maintenance). Analysis of remission will be by intention to treat with stratified Fisher’s exact test statistics.Ethics and dissemination The trial is approved in Leicester (East Midlands – Nottingham Research Ethics Committee (21/EM/0026)), Montreal (McGill University Health Centre Research Ethics Board (RESET for remission/2021-7148)) and Edmonton (University of Alberta Health Research Ethics Board (Pro00101088). Findings will be shared widely (publications, presentations, press releases, social media platforms) and will inform an effectiveness trial.Trial registration number ISRCTN15487120.
