Combining structured exercise with a low-energy diet to attenuate lean mass loss in South Asian adults living with type 2 diabetes: the COMBINE randomised trial protocol.

South Asian adults develop type 2 diabetes at a higher rate, younger age, and lower body mass index than white British counterparts.

• The global prevalence of T2D is rising and disproportionately affects South Asian adults, including those in the United Kingdom.
• South Asians develop T2D at a higher rate and at a younger age than their white British counterparts, at a lower body mass index.
• This disparity motivates the focus on South Asians as an understudied population in intervention research.

Lean mass loss during weight reduction interventions may have physiological and metabolic consequences for people living with type 2 diabetes and obesity.

• A substantial proportion of lean mass is lost while achieving weight loss.
• This lean mass loss may have physiological and metabolic consequences affecting long-term health outcomes and quality of life.
• Active efforts to reduce adiposity can improve glycaemic control and in some cases achieve T2D remission.

The COMBINE trial is a prospective, randomised, two-arm parallel-group, open-label, blinded-endpoint trial conducted in Leicester, UK.

• 36 South Asian adults aged 40-65 years within 10 years of T2D diagnosis and not on insulin therapy will be enrolled.
• The trial compares a combined low energy diet and supervised exercise intervention versus low energy diet alone.
• The trial was approved by the NHS research ethics service (23/WM/0201) and registered as ISRCTN11175684.
• The study is conducted in accordance with the Declaration of Helsinki and all participants provide informed consent prior to enrolment.

Both intervention arms receive an 800-900 kcal/day low energy diet for 12 weeks.

• The low energy diet is prescribed at 800-900 kcal/day for a duration of 12 weeks.
• This dietary intervention is common to both the exercise and control arms.
• Those randomised to the exercise group additionally receive a mixture of supervised and home-based resistance and aerobic exercise training three times per week.

The exercise intervention consists of a mixture of supervised and home-based resistance and aerobic exercise training administered three times per week over 12 weeks.

• The exercise arm receives both resistance and aerobic exercise components.
• Training is delivered as a combination of supervised and home-based sessions.
• Exercise is performed three times per week in addition to the low energy diet.

The primary outcome is the difference in the change of lean mass between groups measured using dual-energy X-ray absorptiometry at baseline and 12 weeks.

• Lean mass will be assessed using dual-energy X-ray absorptiometry (DXA).
• Measurements are taken at baseline and at 12 weeks.
• The primary outcome will be analysed using linear regression modelling.
• The trial is designed to inform a subsequent larger effectiveness trial.