To assess the impact of short-term forearm immobilization on forearm muscle glucose uptake and amino acid net balance and kinetics of individuals with T2D compared with a control group with normoglycaemia.
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Protein and amino acid metabolism disorders NEC
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
•The primary study endpoint is the change in postprandial muscle insulin
sensitivity from 0 to 48 hours, measured as the delta forearm glucose uptake
(FGU) via the arteriovenous forearm balance technique.
Secondary outcome
• Postprandial muscle insulin sensitivity, measured as the temporal response of
forearm glucose uptake (FGU) via arteriovenous forearm balance.
• Forearm amino acid net balance and kinetics (i.e. the rate of appearance and
disappearance) measured via the forearm balance technique and stable isotope
tracer infusion.
• Whole-body substrate oxidation (measured via indirect calorimetry).
Background summary
In the growing group of individuals diagnosed with type 2 diabetes (T2D) in the
Netherlands (estimated to be 1.3 million in 2040), periods of physical
inactivity (e.g. due to hospitalization, diabetes complications, and/or
COVID-19) are increasingly prevalent. Short periods of bedrest or limb
immobilization that are often required for recovery from illness or injury lead
to loss of metabolic health and muscle mass in people with normoglycemia.
People with T2D (who also have low muscle mass and are generally even more
insulin-resistant than their age-matched counterparts) may be similarly or even
more vulnerable to the detrimental effects of physical inactivity. Work
studying the impact of muscle disuse has predominantly been conducted in
individuals without T2D. It is therefore currently unknown how individuals with
T2D respond to physical inactivity.
Study objective
To assess the impact of short-term forearm immobilization on forearm muscle
glucose uptake and amino acid net balance and kinetics of individuals with T2D
compared with a control group with normoglycaemia.
Study design
Controlled trial with parallel group design.
Intervention
Participants with and without T2D will undergo 2 days of forearm immobilization
as a model of local physical inactivity. Before, throughout, and after
immobilization arteriovenous forearm balance measurements will be combined with
intravenous L-[ring-2H5]-phenylalanine infusion to measure muscle glucose
uptake and amino acid balance, uptake, and efflux.
Study burden and risks
The temporary discontinuation of metformin does not pose risks to the
participants.
Insertion of the catheters in a vein is comparable to a normal blood draw and
the only risk is a small local hematoma.
The labeled, non-radioactive amino acid tracer that will be infused
intravenously is produced under sterile conditions according to GMP standards
and is completely safe.
When making the DXA-scan, a very low amount of X-ray radiation is used. The
total exposure to radiation as a result of the DXA scan is so low that it poses
no health risks.
Participants will be asked to keep the casted arm in a sling, so they will not
be able to use their arm during the 2-day immobilization period. This will
impact the ability to do certain activities of daily living, such as eating,
washing dishes, and using the restroom
De Elst 1
Wageningen 6708 WD
NL
De Elst 1
Wageningen 6708 WD
NL
Listed location countries
Age
Inclusion criteria
• Males and females with or without diagnosed type 2 diabetes (diagnosed
at least one year prior)
• Apply lifestyle changes and/or use metformin as oral glucose-lowering
medication as treatment for T2D
• Aged 18-65 years at the time of signing informed consent
• 18.5 < BMI < 30 kg·m2
Exclusion criteria
• Type 1 or a genetic form of diabetes
• Any diagnosed cardiovascular (heart) disease or high blood pressure (>=140
mmHg systolic and/or >=90 mmHg diastolic)
• Chronic use of any prescribed or over-the-counter pharmaceuticals (excluding
oral contraceptives and contraceptive devices)
• Do not consume three regular meals a day (breakfast, lunch, and dinner)
and/or follows a low-carbohydrate diet
• Smoking or chewing tobacco
• Known anaemia
• Regular use of dietary protein and/or amino acid supplements (>3 times per
week)
• Currently involved in a structured progressive resistance training program
(>3 times per week)
• A personal or family history of thrombosis (clots), epilepsy, seizures, or
schizophrenia
• Any previous motor disorders or disorders in muscle and/or lipid metabolism
• History of kidney disease
• History of liver disease
• Pregnant or breastfeeding
• History of any drug or alcohol abuse in the past two years
• Any musculoskeletal injury of the arms in the 12 months before starting the
study
• Claustrophobia
• Unable to give consent
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL87404.028.24 |