Effects of a Multimodal Exercise Program on Physical Performance and Muscle Function in Middle-aged Patients With T2DM

The Effects of a Multimodal Exercise Program on Physical Performance and Muscle Function in Middle-Aged Patients With Type 2 Diabetes: A Multicenter Randomized Controlled Trial

Background Middle-aged adults with type 2 diabetes mellitus (T2DM), especially in Asian populations, are at increased risk of sarcopenia, reduced muscle function, and decline in physical performance. Effective and feasible exercise interventions are needed to support early prevention and healthy aging.

Methods This is a multicenter randomized controlled trial. The study plans to recruit 66 adults aged 45 to 64 years with a confirmed diagnosis of T2DM. Participants will be randomly assigned to either a control group or an intervention group. The control group will receive a Nutrition and Muscle Health Education Sheet and continue routine health management. The intervention group will receive the same education sheet, a Diabetes and Muscle Health Handbook, and a 12-week multimodal exercise program. From Week 13 to Week 24, app-based maintenance reminders will be provided every two weeks.

All participants will be assessed at baseline (Week 0), Week 6, Week 12, and Week 24. The Week 6 assessment is a mid-intervention assessment, the Week 12 assessment evaluates immediate post-intervention effects, and the Week 24 assessment evaluates sustained effects during the maintenance phase. Assessments include physical performance, muscle function, glycated hemoglobin (HbA1c), health-related quality of life, and the risk of sarcopenia. No additional invasive tests or additional research procedures will be introduced at Week 24.

Outcome Measures The primary outcomes are physical performance and muscle function, including the Short Physical Performance Battery (SPPB), Five-Time Sit-to-Stand Test (5TSTS), handgrip strength, and Skeletal Muscle Index (SMI). Secondary outcomes include HbA1c, health-related quality of life measured by the SF-12, and sarcopenia risk assessed by SARC-CalF.

Expected Outcomes This study aims to provide an evidence-based and feasible multimodal exercise prescription for middle-aged adults with T2DM and to support early intervention strategies for healthy aging.

Primary Outcomes

Physical Function:

Physical performance was assessed using the Short Physical Performance Battery (SPPB), which evaluates lower extremity function through three subtests: balance, gait speed, and chair-stand performance. Each component was scored from 0 to 4, with a total score ranging from 0 to 12, where higher scores indicate better physical performance.

The Five-Times Sit-to-Stand Test (5TSTS) was also used to assess lower limb muscle strength and functional mobility. Participants were instructed to rise from a standard chair (seat height 43-45 cm) to a full standing position and return to sitting five consecutive times as quickly as possible without using their arms. The total time required was recorded in seconds, with longer times indicating poorer performance.

Muscle Strength and Mass:

Handgrip strength was measured using a digital dynamometer (e.g., Jamar or equivalent model) as an indicator of upper limb muscle strength. Participants performed the test in a standing position with the arm fully extended at the side and were instructed to exert maximum force for 3-5 seconds. Two trials were performed for each hand, and the highest value (kg) was used for analysis. Low muscle strength was defined according to the Asian Working Group for Sarcopenia (AWGS 2019) criteria (<28 kg for men and <18 kg for women).

Skeletal Muscle Mass Index (SMI) was determined by bioelectrical impedance analysis (BIA; e.g., InBody 720 or equivalent). Appendicular skeletal muscle mass (ASM, kg) was calculated as the sum of lean mass from both arms and legs. SMI was expressed as ASM divided by height squared (kg/m²). Low muscle mass was defined according to the AWGS 2019 cut-off values (<7.0 kg/m² for men and <5.7 kg/m² for women).

Secondary Outcomes

Metabolic Control:

Glycemic control was evaluated by measuring glycated hemoglobin (HbA1c) levels. Venous blood samples were collected after an overnight fast and analyzed using a standardized high-performance liquid chromatography (HPLC) method. HbA1c values were expressed as percentages according to the National Glycohemoglobin Standardization Program (NGSP) guidelines.

Quality of Life:

Health-related quality of life was assessed using the 12-Item Short Form Health Survey (SF-12). This validated questionnaire consists of 12 items covering eight domains, which are summarized into two composite scores: the Physical Component Summary (PCS) and Mental Component Summary (MCS). Scores were calculated according to the standard scoring manual, with higher scores representing better quality of life.

Sarcopenia Risk Assessment:

Risk of sarcopenia was screened using the SARC-CalF questionnaire, which combines the five-item SARC-F (strength, assistance in walking, rising from a chair, climbing stairs, and falls) with calf circumference measurement. Each item of SARC-F was scored from 0 to 2, yielding a total score ranging from 0 to 10. Calf circumference was measured at the widest point of the right leg using a non-elastic tape, with values ≤34 cm for men and ≤33 cm for women, adding 10 points to the SARC-F score. A total SARC-CalF score ≥11 indicated a high risk of sarcopenia.

Inclusion Criteria:

• Diagnosed with Type 2 Diabetes Mellitus and on stable oral hypoglycemic medication.

Middle-aged adults between 45 and 64 years old.

Able to communicate in Mandarin or Taiwanese.

Willing to provide informed consent or have informed consent obtained from a proxy

Exclusion Criteria:

• Limited limb or joint function (e.g., fractures or dislocations).
• Communication or emotional issues, such as depression or mental illness.
• Severe cognitive impairment, such as dementia.
• End-stage renal disease.
• Major comorbidities or complications, including diabetic foot, amputation, myocardial infarction, autonomic neuropathy, and a history of stroke within the last 3 years.