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.

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. 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. 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. ISRCTN15487120.

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© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: MGF is board member, shareholder, and consultant of Circle Cardiovascular Imaging. Through the University Hospitals of Leicester NHS Trust, coinvestigator GM has a research agreement with Circle Cardiovascular Imaging. We will be using software from this company to analyse the cardiac MRI images that we will obtain. KK has received honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, Takeda, Servier, and Pfizer and research support from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, and Pfizer. MJD has acted as consultant, advisory board member and speaker for Novo Nordisk, Sanofi, Lilly and Boehringer Ingelheim, an advisory board member and speaker for AstraZeneca, an advisory board member for Janssen, Lexicon, Servier and Gilead Sciences and as a speaker for Napp Pharmaceuticals, Mitsubishi Tanabe Pharma and Takeda Pharmaceuticals International. She has received grants in support of investigator and investigator initiated trials from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, Astrazeneca and Janssen. TY has received investigator initiated funding for obesity-related research from AstraZeneca.