Exercise Training and Type 2 Diabetes
- Conditions
- Type2diabetes
- Interventions
- Behavioral: Exercise training
- Registration Number
- NCT06478173
- Lead Sponsor
- University of the Faroe Islands
- Brief 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 stratified by gender and medication status, then randomized into a football group (FG) or control group (CG). 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 (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.
- Detailed Description
Background
In recent years, there's been heightened awareness of chronic diseases like type 2 diabetes mellitus (T2DM) and their global impact. T2DM has surged dramatically, with cases quadrupling in the last 30 years. The International Diabetes Federation estimates 451 million cases globally, with projections indicating a rise to 629 million by 2045. In high-income countries, T2DM prevalence peaks in older age groups, and a study from the Faroe Islands shows the same tendency. T2DM is characterized by insulin resistance (often associated with visceral obesity), abnormal insulin secretion, and elevated blood glucose levels. It significantly increases the risk of cardiovascular disease, which is the leading cause of death among T2DM patients.
Studies on T2DM patients demonstrate that 2-3 months of regular aerobic training leads to a significant reduction in visceral fat, ranging from 27% to 45% in men and women. Additionally, physical exercise improves glycemic control, with postprandial blood glucose lowered after aerobic, resistance, or combined training. Combination training, including aerobic and resistance exercises or team sports, is recommended for T2DM patients, offering optimal benefits. High-intensity interval training has shown efficiency in blood glucose regulation. Intensive lifestyle interventions in T2DM patients can markedly improve regulation and increase the likelihood of partial remission compared to general diabetes support programs. Small-sided football game studies demonstrate beneficial effects on fasting plasma glucose and complication markers. Physical fitness protects against all-cause mortality and cardiovascular death. Even low-volume physical activity is associated with a significant reduction in the relative risk of noncommunicable diseases. Recent studies suggest that complex training modes like team sports can provide broad-spectrum health effects, even with volumes lower than WHO recommendations.
Standard treatment for T2DM typically includes dietary guidance and advice on a healthy lifestyle. Medical therapy often includes metformin tablets, a Glucagon-Like Peptide-1 (GLP-1) receptor agonist, and/or a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, and insulin. A large portion of T2DM patients on the Faroe Islands are undergoing GLP-1 receptor agonist or SGLT-2 inhibitor treatment. Studies have shown that these medications are highly effective in improving glucose levels and promoting weight loss. The weight loss mainly involves a decrease in fat mass. However, a review has revealed that the reduction in lean body mass accounts for 20% to 50% of the total weight lost, aligning with weight loss observed with dietary changes and bariatric surgery. Therefore, it is also important to investigate to what extent the positive impact of hybrid training is influenced by GLP-1 receptor agonist and SGLT-2 inhibitor treatment.
Hypothesis
The primary hypothesis is that hybrid training (football) combining endurance, high-intensity interval, and resistance training improves general health status, blood glucose regulation, and muscle metabolism, as well as well-being in patients with T2DM. An exploratory hypothesis is that these changes occur irrespective of GLP-1 receptor agonist and SGLT-2 inhibitor treatment.
Methods
Men and women aged 40-70 diagnosed with T2DM within the last 10 years will be invited. Individuals with severe micro- or macrovascular complications and lactating or pregnant women will be excluded, as further detailed in the full protocol. Extraction from the electronic patient records indicates that approximately 800 individuals meet the criteria.
The study will be designed as a randomized control trial with small-sided football playing as the intervention. In the randomization, there will be stratification based on gender and whether the individuals are undergoing treatment with a GLP-1 receptor agonist and/or an SGLT-2 inhibitor or not. Patients will go through a test battery before (pre-tests) they are randomized into either a football group (FG) or a control group (CG) who will receive standard treatment. After the intervention, participants will undergo the same test battery (post-tests) for evaluation.
Test battery: blood pressure, blood parameters such as HbA1c, plasma glucose, C-peptide, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides, as well as systemic markers of inflammation, bone turnover markers, and urine albumin-to-creatinine ratio test. Body composition will be assessed by dual-energy X-ray absorptiometry (DXA) scans of body fat content, lean body mass, and bone mineralization. The patients will perform a Yo-Yo Intermittent Endurance test level 1 (Yo-Yo IE1) to determine physical fitness. To exclude severe peripheral neuropathy, vibration sensation in the feet will be measured using a biothesiometer along with the pre-tests.
To assess the 24-hour glucose profile, all participants in FG and CG will be provided with a blinded Continuous Glucose Monitoring system (CGM) with two sensors, each designed to last for 14 days. These sensors will be worn consecutively during the initial and final 14 days of the intervention period.
Muscle biopsies will be taken from half of the football group and half of the control group before and after the intervention. The number of biopsies will depend on the total number of participants in the study.
Intervention
The FG group will train in small-sided football games for 60 minutes minimum three times per week for 14 weeks. Training will be intensified from walking football to small-sided game football (3v3-7v7) after two weeks, as described by Krustrup and Krustrup. Trained coaches will be responsible for the training sessions.
Perspective
Additional knowledge about the impact of hybrid training (football), combining endurance, high-intensity interval, and resistance training, on general health status, blood glucose regulation, muscle metabolism, and well-being in patients with T2DM, could form the basis for new recommendations in the treatment of this patient group. Furthermore, there is a need for a comprehensive understanding regarding the impact of hybrid training combined with GLP-1 receptor agonists and SGLT-2 inhibitor treatment in patients with T2DM.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 126
- Diagnosed with type 2 diabetes within ten years of study recruitment
- Diabetic retinopathy (expect mild non-proliferative retinopathy or early proliferative retinopathy
- Macro-albuminuria (urine albumin-creatinine ratio ≥ 300 mg/g)
- Nepropathy (plasma creatinine ≥ 130 μM)
- Diabetic neuropathy (except mild affected vibratory testing (<50 V)
- History of ischemic heart disease
- History or signs of arterial insufficiency
- Steroid treatment within 3 months of baseline examination
- Thyroid disease
- Inability or contraindication to increased levels of physical activity
- Anaemia (haemoglobin < 7.3 mmol/L (women) and 8.3 mmol/L (men)
- Signs of kidney disease
- Pregnancy or breast feeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Exercise training Exercise training Patients in the exercise group will engage in supervised soccer training 3 times a week for 14 weeks.
- Primary Outcome Measures
Name Time Method Lean mass (kg) Change from baseline to end-of-intervention (14 weeks) Lean mass will be measured using Dual-energy X-ray absorptiometry (DXA) scans
- Secondary Outcome Measures
Name Time Method C-terminal telopeptide of type 1 collagen (ng/ml) Change from baseline to end-of-intervention (14 weeks) C-terminal telopeptide of type 1 collagen will be measured from blood samples.
Fasting plasma glucose (mmol/L) Change from baseline to end-of-intervention (14 weeks) Fasting plasma glucose will be measured from blood samples in a fasting state
Peak oxygen uptake (mL/min) Change from baseline to end-of-intervention (14 weeks) Peak oxygen uptake will be measured on a bicycle ergometer
Glycosylated hemoglobin A1c (HbA1c) (mmol/mol) Change from baseline to end-of-intervention (14 weeks) HbA1c will be measured from blood samples in a fasting state
C-peptide (nmol/L) Change from baseline to end-of-intervention (14 weeks) C-peptide will be measured from blood samples in a fasting state
24h glycemic variability Change from baseline to end-of-intervention (14 weeks) Measured using continuous glucose monitors (CGM) during weeks 1 and 2 and weeks 13 and 14
Body fat percentage (%) Change from baseline to end-of-intervention (14 weeks) Body fat percentage will be measured using Dual-energy X-ray absorptiometry (DXA) scans
Body fat mass (kg) Change from baseline to end-of-intervention (14 weeks) Body fat mass will be measured using Dual-energy X-ray absorptiometry (DXA) scans
Body weight (kg) Change from baseline to end-of-intervention (14 weeks) Body weight will be measured to the nearest 0.1 kg. in a fasting state without shoes and wearing light clothes.
Waist and hip circumference (cm) Change from baseline to end-of-intervention (14 weeks) Waist and hip circumference will be measured in duplicate after gentle expiration.
Blood pressure (mmHg) Change from baseline to end-of-intervention (14 weeks) 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.
Resting heart rate (bpm) Change from baseline to end-of-intervention (14 weeks) 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.
Lipid profile (mmol/L) Change from baseline to end-of-intervention (14 weeks) 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.
Lipoprotein (a) (nmol/L) Change from baseline to end-of-intervention (14 weeks) Lipoprotein (a) will be measured from blood samples in a fasting state
Apolipoprotein B (nmol/L) Change from baseline to end-of-intervention (14 weeks) Apolipoprotein B will be measured from blood samples in a fasting state
World Health Organization Quality of Life - BREF instrument (scale score 0-100) Change from baseline to end-of-intervention (14 weeks) 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.
Warwick-Edinburgh Mental Well-being Scale (scale score 14-70) Change from baseline to end-of-intervention (14 weeks) 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
Cardiorespiratory fitness (m) Change from baseline to end-of-intervention (14 weeks) Cardiorespiratory fitness will be evaluated using the Yo-Yo intermittent endurance test level 1.
Jump and balance Change from baseline to end-of-intervention (14 weeks) 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.
Procollagen type 1 N propeptide (ng/ml) Change from baseline to end-of-intervention (14 weeks) Procollagen type 1 N propeptide will be measured from blood samples.
Osteocalcin (ng/ml) Change from baseline to end-of-intervention (14 weeks) Osteocalcin will be measured from blood samples
Bone mineral density (g/cm2) Change from baseline to end-of-intervention (14 weeks) Bone mineral density will be measured using Dual-energy X-ray absorptiometry (DXA) scans
Bone mineral content (g) Change from baseline to end-of-intervention (14 weeks) Bone mineral content will be measured using Dual-energy X-ray absorptiometry (DXA) scans
Skeletal muscle mitochondrial oxidative capacity (µmol/g/min) Change from baseline to end-of-intervention (14 weeks) Skeletal muscle oxidative capacity will be evaluated as maximal 3-hydroxy-acetylCoa-dehydrogenase and citrate synthase activity (µmol/g/min)
Skeletal muscle glucose transport capacity Change from baseline to end-of-intervention (14 weeks) Skeletal muscle glucose transport capacity will be evaluated as GLUT-4 protein expression
Trial Locations
- Locations (1)
University of the Faroe Islands
🇫🇴Tórshavn, Faroe Islands