The Muscle Phenotype and Cardiometabolic Health Monitoring Project
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 250
- 试验地点
- 1
- 主要终点
- Whole-body insulin sensitivity
研究概览
简要总结
Insulin resistance is an early etiological factor in the development of type-2 diabetes (T2D), which constitutes a large societal health burden with an expected additional rise in the years to come.
Skeletal muscle is the body's largest lean tissue mass and the major site of glucose disposal in response to insulin stimulation. Prior studies have suggested that a fast skeletal muscle phenotype, including a predominant fast muscle fiber composition, reduced capillary density, low fat oxidation and muscle oxidative capacity may be implicated in insulin resistance and TD2 development. However, key questions pertain in relation to the cause and effect of these relationships as well as the interaction with potential confounders and effect-modifiers including life-style factors (e.g. diet and physical activity levels) and general participant characteristics (e.g. body composition and training status).
In the present project, we therefore aim to derive muscle fiber type and extensively map the proteomic signature of the early stages of insulin resistance in a large cross-sectional study using a young and apparently healthy cohort prior to T2D development, including a thorough participant characterization. We will recruit ~250 participants (men and women) in the age of 20-30 years and conduct extensive phenotyping and tissue sampling across one laboratory-based test day and a scan visit, as well as measurements of physical activity level and glucose handling in free-living conditions with wearable sensors.
The study has a longitudinal aspect as participants will be re-invited at 5-year intervals for up to 20 years to delineate the trajectory of metabolic health in relation to muscle phenotype measures.
The results of the project are expected to lead to significant advancements in our understanding of the importance of muscle phenotype for early-stage insulin resistance and metabolic health trajectories. Such understanding has potentially important clinical implications, as it can open new avenues for targeted interventions and individualized early preventive strategies to counter or delay the progression of insulin resistance and associated metabolic and cardiovascular disorders.
详细描述
The project is composed of 1) a screening visit to determine study eligibility, 2) a main test day in the lab, 3) 10 days of physical activity tracking and continuous glucose monitoring in free-living conditions and 4) a scan visit including a whole-body MRI scan and lower leg pQCT scan.
For the main lab visit the participants will arrive in the morning after an overnight fast. This visit includes measurements of anthropometrics, resting metabolic rate, resting heart rate + heart rate variability, arterial stiffness, intima media thickness, as well as blood pressure obtained in the supine position. In addition, a fasting blood sample will be obtained followed by a 2-h glucose tolerance test with concomitant questionnaires provided in writing on basic demographics, physical activity level, sleep, stress and mental health. Two thigh muscle biopsies and a subcutaneous adipose tissue fat sample from the abdominal region will be obtained, while maximal voluntary knee-extensor contraction torque and rate of force development will be measured. Lastly, cycling-based assessments of maximal fat oxidation rate, peak power and maximal oxygen uptake will be assessed using indirect calorimetry including capillary lactate samples.
The scan visit will consist of an MRI whole-body scan, soleus and gastrocnemius 1H-MRS and a pQCT bone scan of the lower limb at 4% and 66% of the total bone length.
The objective measurements of physical activity levels and glucose-handling capacity will be performed for 10 days in free-living conditions using feasibly worn sensors (continuous glucose monitor and thigh-worn accelerometer). During this time, a food dairy needs to be filled in during two week days and one weekend day to estimate the habitual food intake.
A standardized evening meal will be provided prior to the laboratory-based test day and a standardized lunch meal served during the testing day.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 20 Years 至 30 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Sex: Males and females
- •Age: 20-30 years
- •Healthy (no diagnosed chronic disease)
排除标准
- •Chronic disease deemed to affect study outcomes
- •Disease that increase haemorrhage risk
- •Daily intake of medication that could confound study outcomes
- •Regular smokers
- •Active pregnancy
- •Immobilization (inactivity due to injury or illness, e.g. cast or brace) for more than a week in the month prior to the study or for more than 4 weeks in the past 6 months prior to the study
- •Very high structured physical exercise level (>10 h/week).
- •Participants not willing to adhere to standardized meal prescriptions included in the study protocols will also be excluded (due to e.g. allergies or specific dietary preferences)
结局指标
主要结局
Whole-body insulin sensitivity
时间窗: At baseline and at 5-year intervals for up to 20 years
The Matsuda index derived from an oral glucose tolerance test
次要结局
- Skeletal muscle fiber type(At baseline and at 5-year intervals for up to 20 years)
- Molecular skeletal muscle profile(At baseline and at 5-year intervals for up to 20 years)
- MRI-derived muscle and fat volumes(At baseline and at 5-year intervals for up to 20 years)
- MRI derived tissue fat infiltration(At baseline and at 5-year intervals for up to 20 years)
- Physical activity level(At baseline and at 5-year intervals for up to 20 years)
- HOMA-IR(At baseline and at 5-year intervals for up to 20 years)
- Cardiorespiratory fitness(At baseline and at 5-year intervals for up to 20 years)
- Muscle strength(At baseline and at 5-year intervals for up to 20 years)
- Free-living glycaemic control(At baseline and at 5-year intervals for up to 20 years)
- Dietary intake(At baseline and at 5-year intervals for up to 20 years)
- Subcutaneous adipose tissue phenotyping(At baseline and at 5-year intervals for up to 20 years)
- Maximal fat oxidation rate(At baseline and at 5-year intervals for up to 20 years)
- Pulsewave velocity(At baseline and at 5-years intervals for up to 20 years)
- Resting heart rate(At baseline and at 5-year intervals for up to 20 years)
- Heart rate variability(At baseline and at 5-year intervals for up to 20 years)