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.

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.

Relative protein intake and associations with markers of physical function in those with type 2 diabetes.

AIMS: To examine the independent associations between relative protein intake (g kg-1  day 1 ) and markers of physical function in those with type 2 diabetes, while also comparing with current guidelines for protein intake. METHODS: This analysis reports data from the ongoing Chronotype of Patients with Type 2 Diabetes and Effect on Glycaemic Control (CODEC) study. Functional assessments included: Short Physical Performance Battery (SPPB), 60 s sit-to-stand (STS-60), 4-m gait speed, time to rise from a chair (×5) and handgrip strength. Participants also completed a self-reported 4 day diet diary. Regression analyses assessed whether relative protein intake was associated with markers of physical function. Interaction terms assessed whether the associations were modified by sex, age, HbA1c or body mass index (BMI). RESULTS: 413 participants were included (mean ± SD:age = 65.0 ± 7.7 years, 33% female, BMI = 30.6 ± 5.1 kg/m2 ). The average total protein intake was 0.88 ± 0.31 g kg-1  day-1 . 33% of individuals failed to meet the reference nutrient intake for the United Kingdom (≥0.75 g kg-1  day-1 ), and 87% for European recommendations (≥1.2 g kg-1  day-1 ). After adjustment, each 0.5 g/kg of protein intake was associated with an 18.9% (95% CI: 2.3, 35.5) higher SPPB score, 22.7% (1.1, 44.3) more repetitions in STS-60, 21.1% (4.5, 37.7) faster gait speed and 33.2% (16.9, 49.5) lower chair rise time. There were no associations with handgrip strength or any interactions. CONCLUSIONS: Relative protein intake was positively associated with physical function outcomes, even after consideration of total energy intake. As a number of individuals were below the current guidelines, protein intake may be a modifiable factor of importance for people with type 2 diabetes.