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.
Sex: Males and females
Age: 20-30 years
BMI <35
Healthy (no diagnosed chronic disease)
Chronic disease deemed to affect study outcomes
Disease that increase haemorrhage risk
Daily intake of medication that could confound study outcomes
Regular smokers
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.
Cohort
Prospective
Not listed
Whole-body insulin sensitivity
The Matsuda index derived from an oral glucose tolerance test
Skeletal muscle fiber type
Skeletal muscle fiber type assessed using SDS page
Molecular skeletal muscle profile
Molecular profiling of skeletal muscle tissue, including proteomic and related pathway-level analyses relevant to metabolic function.
MRI-derived muscle and fat volumes
Whole-body MRI-derived muscle and fat volumes at the total and regional body level
MRI derived tissue fat infiltration
Whole-body MRI-derived tissue fat infiltration in the liver, intermuscular and intramuscular area
Blood pressure
Systolic and diastolic blood pressure obtained using a sphygmomanometer
10 s sprint peak and average power
Peak and average power output during a 10 s sprint test
Lactate accumulation
Lactate accumulation during a 10 s cycling sprint test
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
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University Ghent
Lead sponsor
University Hospital, Ghent
Collaborator
