Independent and combined effects of mediterranean diet and ultra-processed food reduction within cardiac rehabilitation on cardiometabolic health: the DIABEPIC Reform randomized controlled trial

Background The world faces a growing epidemic of chronic diseases and obesity. Despite advances in treatment, metabolic diseases continue to impose a major cardiovascular burden. Ultra-processed foods (UPF) account for ~45% of adults’ daily caloric intake and may contribute to up to 38% of Canadian national cardiovascular disease burden. Yet, no randomized controlled trial has tested if reducing UPF intake prevents or reverses cardiometabolic diseases. The DIABEPIC-1 and -2 pilot trials demonstrated that integrating nutritional strategies (Mediterranean diet, time-restricted eating, and reduction of UPF intake) within a cardiac rehabilitation program may achieve significant reductions in waist circumference, visceral fat mass and body mass, and promising remission rates of prediabetes, type 2 diabetes (T2D), and metabolic syndrome. Purpose Building on this work, the DIABEPIC Reform trial will aim to evaluate the independent and combined effects of Mediterranean diet and UPF reduction within a structured cardiac rehabilitation program on sustainable body mass loss and remission of prediabetes, T2D, and obesity. Methods DIABEPIC Reform will be a 12-month, three-arm, parallel-group randomized controlled trial. Ninety-nine adults with preclinical or clinical obesity referred to cardiac rehabilitation will be randomized (1:1:1) to one of three interventions: (1) Mediterranean diet, (2) targeted UPF reduction, or (3) combined Mediterranean diet + targeted UPF reduction. All participants will receive standard cardiac rehabilitation, including 36 supervised exercise sessions, four one-hour personalized nutrition counselling sessions with a dietitian, and will have access to a moderated intervention-specific social network group. Assessments will be conducted at baseline, 3 months, 6 months, and 12 months, including: body composition by bioimpedance; resting blood pressure; cardiorespiratory fitness through a maximal exercise test; glycemic, lipid, and hepatic profiles with blood tests; dietary habits assessed with food diaries and food frequency questionnaires. Some measures will evaluate remission of prediabetes, T2D, and obesity. The primary analysis (intention-to-treat) will compare 6-month body mass loss between the combined strategy and each single strategy using linear mixed models. Remission endpoints will be analyzed via logistic regression. Anticipated results: Combining Mediterranean diet and UPF reduction should produce synergistic effects on body mass loss, metabolic improvement, and remission rates, exceeding the benefits of either approach alone. Conclusion The DIABEPIC Reform study is a novel and pragmatic clinical trial designed to address one of the most pressing nutritional challenges in Canada. By targeting a reduction of UPF, this study aims to generate the first randomized evidence that focusing on food processing, alongside traditional dietary quality, prevents and potentially reverses diet-related cardiometabolic diseases.