The Muscle Monitor: Early Skeletal Muscle Indicators of Insulin Resistance and Cardiometabolic Risk (MUSCLE MONITOR)

The Muscle Phenotype and Cardiometabolic Health Monitoring Project

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.

Study Overview

• Status: Recruiting
• Conditions: Physical Activity; Insulin Resistance; Insulin Resistance and Type 2 Diabetes; Cardiometabolic Risk Factors; Muscle Fiber Type

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Eline Lievens, Professor; Phone Number: 00320478312585; Email: eline.lievens@ugent.be
• Study Contact Backup: Name: Jeppe Foged Vigh-Larsen, PhD; Phone Number: 004529870635; Email: jeppefoged.vighlarsen@ugent.be

Study Locations

• Belgium
  • East Flanders
    • Ghent, East Flanders, Belgium, 9000
      • Recruiting
      • Ghent University
      • Contact: Eline Lievens, Professor; Phone Number: 00320478312585; Email: eline.lievens@ugent.be
      • Contact: Jeppe Foged Vigh-Larsen, PhD; Email: jeppefoged.vighlarsen@ugent.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from the greater Ghent area (Belgium) using recruitment materials including posters mounted on relevant locations (e.g. educational sites) and circulated on social media (e.g. Facebook, Linkedin, Twitter). The Gent University volunteer register of people who have expressed interest in participating in research studies will also be used.

Description

Inclusion Criteria:

• Sex: Males and females
• Age: 20-30 years
• BMI <35
• Healthy (no diagnosed chronic disease)

Exclusion Criteria:

• 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)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Whole-body insulin sensitivity	The Matsuda index derived from an oral glucose tolerance test	At baseline and at 5-year intervals for up to 20 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skeletal muscle fiber type	Skeletal muscle fiber type assessed using SDS page	At baseline and at 5-year intervals for up to 20 years
Molecular skeletal muscle profile	Molecular profiling of skeletal muscle tissue, including proteomic and related pathway-level analyses relevant to metabolic function.	At baseline and at 5-year intervals for up to 20 years
MRI-derived muscle and fat volumes	Whole-body MRI-derived muscle and fat volumes at the total and regional body level	At baseline and at 5-year intervals for up to 20 years
MRI derived tissue fat infiltration	Whole-body MRI-derived tissue fat infiltration in the liver, intermuscular and intramuscular area	At baseline and at 5-year intervals for up to 20 years
Physical activity level	Accelerometer-based physical activity levels	At baseline and at 5-year intervals for up to 20 years
HOMA-IR	Homeostatic Model Assessment of Insulin Resistance based on fasted blood sampling	At baseline and at 5-year intervals for up to 20 years
Cardiorespiratory fitness	Maximal oxygen uptake assessed using indirect calorimetry during incremental cycling	At baseline and at 5-year intervals for up to 20 years
Muscle strength	Maximal voluntary isometric contraction torque assessed in a dynamometer	At baseline and at 5-year intervals for up to 20 years
Free-living glycaemic control	Continuous glucose monitoring-derived glycaemic metrics during free-living conditions	At baseline and at 5-year intervals for up to 20 years
Dietary intake	Dietary intake assessed using repeated 24-hour food diaries and food frequency questionnaires, including estimates of energy intake and macronutrient composition.	At baseline and at 5-year intervals for up to 20 years
Subcutaneous adipose tissue phenotyping	Proteomics derived measures of adipose tissue phenotype	At baseline and at 5-year intervals for up to 20 years
Maximal fat oxidation rate	Maximal fat oxidation rate obtained using indirect calorimetry during incremental cycling	At baseline and at 5-year intervals for up to 20 years
Pulsewave velocity	Carotid-femoral pulsewave velocity measured using Doppler echocardiography with ECG gating	At baseline and at 5-years intervals for up to 20 years
Resting heart rate	Resting heart rate assessed using a chest-worn heart rate monitor	At baseline and at 5-year intervals for up to 20 years
Heart rate variability	Heart rate variability assessed using a chest-worn heart rate monitor	At baseline and at 5-year intervals for up to 20 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure	Systolic and diastolic blood pressure obtained using a sphygmomanometer	At baseline and at 5-year intervals for up to 20 years
10 s sprint peak and average power	Peak and average power output during a 10 s sprint test	At baseline and at 5-year intervals for up to 20 years
Lactate accumulation	Lactate accumulation during a 10 s cycling sprint test	At baseline and at 5-year intervals for up to 20 years
Blood lipid profile	Including measures of triglycerides, free fatty acids, lipoprotein (a), cholesterol, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol	At baseline and at 5-year intervals for up to 20 years
Bone measurements	Bone density assessed using peripheral quantitative computed tomography (pQCT).	At baseline and at 5-year intervals for up to 20 years

Collaborators and Investigators

• Sponsor: University Ghent
• Collaborators: University Hospital, Ghent

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2025
• Primary Completion (Estimated): December 31, 2046
• Study Completion (Estimated): December 31, 2046

Study Registration Dates

• First Submitted: February 12, 2026
• First Submitted That Met QC Criteria: June 24, 2026
• First Posted (Actual): July 1, 2026

Study Record Updates

• Last Update Posted (Actual): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Physical activity; Insulin sensitivity; Skeletal muscle
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Hyperinsulinism; Behavior; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Insulin Resistance; Motor Activity
• Other Study ID Numbers: ONZ-2024-0588

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No