Exercise Training and Type 2 Diabetes
NCT Number: NCT06478173
Status: ACTIVE_NOT_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Type2diabetes
Interventions: BEHAVIORAL: Exercise training
Sponsor: University of the Faroe Islands
Collaborators: National Hospital of the Faroe Islands|University of Copenhagen
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 126
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: OTHER
Start Date: 2024-08-01
Completion Date: 2026-08-01
Locations: University of the Faroe Islands, Tórshavn, 110, Faroe Islands

Summary:
Objective: This study investigates the effects of hybrid training in the form of small-sided football games on health status, blood glucose regulation, muscle metabolism, and well-being in patients with type 2 diabetes mellitus (T2DM), with additional focus on the impact of concurrent treatment with Glucagon-Like Peptide-1 receptor agonists and Sodium-Glucose Co-Transporter-2 inhibitors.

Background: T2DM prevalence has surged globally, characterized by insulin resistance, abnormal insulin secretion, and elevated blood glucose levels, significantly increasing cardiovascular disease risk. Physical activity is known to reduce visceral fat, improve glycaemic control, and lower cardiovascular mortality. However, the interaction between hybrid training and T2DM medication effects remains underexplored.

Methods: A randomized controlled trial will be conducted with men and women aged 40-70 diagnosed with T2DM within the last 10 years. Exclusion criteria include severe micro- or macrovascular complications and pregnancy. Participants (n=800) will be invited and enrolled participants will be randomized in a 60/40 ratio into a football group (FG) or control group (CG), using a stratified randomization approach. Stratification will be based on age, gender and GLP-1 agonist treatment. The FG will engage in 60-minute small-sided football sessions three times per week for 14 weeks. Both groups will undergo pre- and post-intervention assessments, including blood pressure, blood parameters, body composition via dual-energy X-ray absorptiometry scans, physical fitness (Peak oxygen uptake and Yo-Yo Intermittent Endurance Test Level 1), and 24-hour glucose profiling using Continuous Glucose Monitoring systems. Muscle biopsies will be collected from a subset of participants.

Conclusion: This study aims to provide insights into the benefits of hybrid training for T2DM patients, potentially informing new treatment guidelines that integrate exercise and pharmacotherapy to optimize health outcomes.

Primary Outcome Measures: Lean mass (kg), Lean mass will be measured using Dual-energy X-ray absorptiometry (DXA) scans, Change from baseline to end-of-intervention (14 weeks)
Secondary Outcome Measures: Fasting plasma glucose (mmol/L), Fasting plasma glucose will be measured from blood samples in a fasting state, Change from baseline to end-of-intervention (14 weeks)|Peak oxygen uptake (mL/min), Peak oxygen uptake will be measured on a bicycle ergometer, Change from baseline to end-of-intervention (14 weeks)|Glycosylated hemoglobin A1c (HbA1c) (mmol/mol), HbA1c will be measured from blood samples in a fasting state, Change from baseline to end-of-intervention (14 weeks)|C-peptide (nmol/L), C-peptide will be measured from blood samples in a fasting state, Change from baseline to end-of-intervention (14 weeks)|24h glycemic variability, Measured using continuous glucose monitors (CGM) during weeks 1 and 2 and weeks 13 and 14, Change from baseline to end-of-intervention (14 weeks)|Body fat percentage (%), Body fat percentage will be measured using Dual-energy X-ray absorptiometry (DXA) scans, Change from baseline to end-of-intervention (14 weeks)|Body fat mass (kg), Body fat mass will be measured using Dual-energy X-ray absorptiometry (DXA) scans, Change from baseline to end-of-intervention (14 weeks)|Body weight (kg), Body weight will be measured to the nearest 0.1 kg. in a fasting state without shoes and wearing light clothes., Change from baseline to end-of-intervention (14 weeks)|Waist and hip circumference (cm), Waist and hip circumference will be measured in duplicate after gentle expiration., Change from baseline to end-of-intervention (14 weeks)|Blood pressure (mmHg), Systolic- and diastolic blood pressure will be measured in duplicate from the non-dominant arm with a digital blood pressure monitor in sitting position after at least 5 min of rest., Change from baseline to end-of-intervention (14 weeks)|Resting heart rate (bpm), Resting heart rate will be measured in duplicate from the non-dominant arm with a digital blood pressure monitor in sitting position after at least 5 min of rest., Change from baseline to end-of-intervention (14 weeks)|Lipid profile (mmol/L), Total cholesterol (mmol/L), low-density lipoprotein-cholesterol (mmol/L), high-density lipoprotein cholesterol (mmol/l) and triglycerides (mmol/l) will be measured from blood samples in a fasting state., Change from baseline to end-of-intervention (14 weeks)|Lipoprotein (a) (nmol/L), Lipoprotein (a) will be measured from blood samples in a fasting state, Change from baseline to end-of-intervention (14 weeks)|Apolipoprotein B (nmol/L), Apolipoprotein B will be measured from blood samples in a fasting state, Change from baseline to end-of-intervention (14 weeks)|World Health Organization Quality of Life - BREF instrument (scale score 0-100), Quality of life will be evaluated with a Faroese version of the World Health Organization Quality of Life - BREF instrument (WHOQOL-BREF), which ranges from 1-5 for individual items and 0-100 for the overall domain scores with higher scores reflecting a higher quality of life., Change from baseline to end-of-intervention (14 weeks)|Warwick-Edinburgh Mental Well-being Scale (scale score 14-70), Mental well-being will be evaluated with a Faroese version of the Warwick-Edinburgh Mental Well-Being Scale, which is a 14-item scale covering subjective well-being and psychological functioning. The scale is scored by summing responses to each item answered on a 1 to 5 Likert scale. The minimum scale score is 14 and the maximum is 70. A high score indicates good mental well-being whereas a low score indicates poor mental well-being, Change from baseline to end-of-intervention (14 weeks)|Cardiorespiratory fitness (m), Cardiorespiratory fitness will be evaluated using the Yo-Yo intermittent endurance test level 1., Change from baseline to end-of-intervention (14 weeks)|Jump and balance, Countermovement jump and balance (bilateral quiet stand for 30 seconds with eyes open and one attempt with eyes closed as well as single leg stand for 15 seconds with hands on the hips and one foot raised) will be evaulated using the VALD Forcedeck force plates., Change from baseline to end-of-intervention (14 weeks)|C-terminal telopeptide of type 1 collagen (ng/ml), C-terminal telopeptide of type 1 collagen will be measured from blood samples., Change from baseline to end-of-intervention (14 weeks)|Procollagen type 1 N propeptide (ng/ml), Procollagen type 1 N propeptide will be measured from blood samples., Change from baseline to end-of-intervention (14 weeks)|Osteocalcin (ng/ml), Osteocalcin will be measured from blood samples, Change from baseline to end-of-intervention (14 weeks)|Bone mineral density (g/cm2), Bone mineral density will be measured using Dual-energy X-ray absorptiometry (DXA) scans, Change from baseline to end-of-intervention (14 weeks)|Bone mineral content (g), Bone mineral content will be measured using Dual-energy X-ray absorptiometry (DXA) scans, Change from baseline to end-of-intervention (14 weeks)|Skeletal muscle mitochondrial oxidative capacity (µmol/g/min), Skeletal muscle oxidative capacity will be evaluated as maximal 3-hydroxy-acetylCoa-dehydrogenase and citrate synthase activity (µmol/g/min), Change from baseline to end-of-intervention (14 weeks)|Skeletal muscle glucose transport capacity, Skeletal muscle glucose transport capacity will be evaluated as GLUT-4 protein expression, Change from baseline to end-of-intervention (14 weeks)
Other Outcome Measures: Systemic markers of inflammation (fg/mL), Interferon gamma (fg/mL), tumor necrosis factor alpha (fg/mL) and interleukins 1beta, 2, 6, 8, 10 (fg/mL) will be measured from blood samples, Change from baseline to end-of-intervention (14 weeks)|White blood cell count (×10^9/L), White blood cell count will be measured from blood samples, Change from baseline to end-of-intervention (14 weeks)|C-reactive protein (mg/L), C-reactive protein will be measured from blood samples, Change from baseline to end-of-intervention (14 weeks)|skeletal muscle muscle capillarization, Skeletal muscle muscle capillarization will be evaluated from immunohistochemical staining of muscle biopsies, Change from baseline to end-of-intervention (14 weeks)|Myofibre cross-sectional area, Myofibre cross-sectional area will be evaluated from immunohistochemical staining of muscle biopsies, Change from baseline to end-of-intervention (14 weeks)|Skeletal muscle glycogen content (mmol kg-1 d.w.), For the biochemical assessment of whole-muscle glycogen content, muscle tissue will be freeze-dried and dissected free of blood and connective tissue, and analyzed spectrophotometrically., Change from baseline to end-of-intervention (14 weeks)