Clinical trial NCT06478173: Exercise Training and Type 2 Diabetes
Official title: The Effect of Complex Exercise Training on General Health Status in Patients with Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type2diabetes
Keywords: Type2diabetes
Exercise training
Health
Adaptation, physiological
Lead sponsor: University of the Faroe Islands
Sponsor class: OTHER
Collaborators: name: National Hospital of the Faroe Islands
name: University of Copenhagen
First posted: 2024-06-27
Enrollment: 126
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The participants are randomized in a 60:40 ratio to 1) exercise training or 2) control, using a stratified randomization approach. Stratification will be based on gender (male/female), age (≥55 years vs. \<55 years), and GLP-1 agonist use (yes/no) to ensure that the distribution of gender, age, and GLP-1 agonist use is balanced across the two groups.
Primary purpose: OTHER

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 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.

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 age (≥55 yrs/\<55 yrs), gender (male/female) and whether the individuals are undergoing treatment with a GLP-1 receptor agonist or not (treatment/non-treatment). 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 Peak oxygen uptake test on a cycling ergometer as well as 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.

Finally, muscle biopsies will be obtained from a random subset of participants allocated to the FG (10 males and 10 females treated with GLP-1 and 10 males and 10 females not treated with GLP-1) in order to assess the potential impact of GLP-1 on training-induced adaptations in skeletal muscle.

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.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with type 2 diabetes within ten years of study recruitment

Exclusion Criteria:

* 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

Primary outcomes:
measure: Lean mass (kg)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
Secondary outcomes:
measure: Fasting plasma glucose (mmol/L)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Peak oxygen uptake (mL/min)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Glycosylated hemoglobin A1c (HbA1c) (mmol/mol)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: C-peptide (nmol/L)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: 24h glycemic variability
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Body fat percentage (%)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Body fat mass (kg)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Body weight (kg)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Waist and hip circumference (cm)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Blood pressure (mmHg)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Resting heart rate (bpm)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Lipid profile (mmol/L)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Lipoprotein (a) (nmol/L)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Apolipoprotein B (nmol/L)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: World Health Organization Quality of Life - BREF instrument (scale score 0-100)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Warwick-Edinburgh Mental Well-being Scale (scale score 14-70)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Cardiorespiratory fitness (m)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Jump and balance
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: C-terminal telopeptide of type 1 collagen (ng/ml)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Procollagen type 1 N propeptide (ng/ml)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Osteocalcin (ng/ml)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Bone mineral density (g/cm2)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Bone mineral content (g)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Skeletal muscle mitochondrial oxidative capacity (µmol/g/min)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Skeletal muscle glucose transport capacity
timeFrame: Change from baseline to end-of-intervention (14 weeks)
Other outcomes:
measure: Systemic markers of inflammation (fg/mL)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: White blood cell count (×10^9/L)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: C-reactive protein (mg/L)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: skeletal muscle muscle capillarization
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Myofibre cross-sectional area
timeFrame: Change from baseline to end-of-intervention (14 weeks)
measure: Skeletal muscle glycogen content (mmol kg-1 d.w.)
timeFrame: Change from baseline to end-of-intervention (14 weeks)
Locations:
city: Tórshavn
country: Faroe Islands
facility: University of the Faroe Islands
Study officials:
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