- to investigate the difference in diacylglycerol species and subcellular localisation in athletes, sedentary insulin sensitive subjects and sedentary insulin resistant subjects. - to investigate the potential effect of alternative DAG localization…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Skeletal muscle content of DAG species and subcellular partitioning in
athletes, sedentary insulin sensitive subjects and sedentary insulin resistant
subjects (measured in muscle biopsies).
- Activation and isotype form of protein kinase C in athletes, sedentary
insulin sensitive subjects and sedentary insulin resistant subjects (measured
in muscle biopsies at baseline and after insulin stimulation).
Secondary outcome
- IMCL by 1H-Magnetic Resonance Spectroscopy
- Insulin sensitivity by implementing a 1-step hyperinsulinemic-euglycemic
clamp.
- Metabolites in blood before and during insulin stimulation (i.e. glucose,
free fatty acids, triglycerides, cholesterol, insulin)
Background summary
Fat accumulation in skeletal muscle is associated with the development of type
2 diabetes mellitus. Indeed, type 2 diabetes patients (T2DM) have increased
levels of intramyocellular lipids (IMCL). Paradoxically, however, endurance
trained athletes are also characterized by elevated levels of IMCL, while being
highly insulin sensitivity. This paradox has been called the athletes paradox,
and has so far not been explained. Here, we aim to investigate the levels and
localization of diacylglycerol - a fatty acid intermediate that is able to
impair insulin signaling - in sedentary insulin resistant subjects and
endurance trained athletes, with similar IMCL content, and compare them to a
group of sedentary but insulin sensitive subjects.
Study objective
- to investigate the difference in diacylglycerol species and subcellular
localisation in athletes, sedentary insulin sensitive subjects and sedentary
insulin resistant subjects.
- to investigate the potential effect of alternative DAG localization on
insulin signaling in the three groups by investigating activation and isotype
form of protein kinase C in athletes, sedentary insulin sensitive subjects and
sedentary insulin resistant subjects.
Study design
The current study is an international multicenter, exploratory, cross-sectional
study without intervention.
Study burden and risks
Subjects will first visit the University once for screening purposes during
which length, body weight and blood pressure will be measured. An ECG will be
performed, blood will be drawn, and subjects will fill in 2 questionnaires. An
oral glucose tolerance test will be performed, to determine whether the
subjects are insulin sensitive or insulin resistant, by calculating OGIS
values. The second screening day will contain a maximal cycling test, after
approval of the dependent physician (based on the outcomes of screening day 1).
If screening was successfully completed and a subject fulfils the inclusion
criteria, the subject can participate in the study. The subjects will be
divided into one of the three study groups (based on the results of the maximal
cycling test and OGTT) and be invited for the first test day. The first test
day at the university will be in the morning (fasted) for a DEXA scan (body
composition measurement) and a non-invasive measurement of intramyocellular
lipid content using magnetic resonance spectroscopy (MRS). On the second test
day, subjects will come to the university after an overnight fast and a muscle
biopsy will be taken and resting energy expenditure will be measured.
Subsequently, subjects will undergo a 1-step hyperinsulinemic-euglycemic clamp.
Furthermore, during the clamp, a second muscle biopsy will be obtained. For all
visits, subjects have to report to the university in the morning in the fasted
state, except for the second screening day. The evenings prior to the last test
day, subjects have to eat a standardized meal. Muscle biopsies can cause mild
discomfort and there is a risk of hematoma. During the
hyperinsulinemic-euglycemic clamp, a risk of hypoglycaemia exists. In total, we
will draw approximately 206 ml blood during the entire study period.
Universiteitssingel 50
Maastricht 6229 ER
NL
Universiteitssingel 50
Maastricht 6229 ER
NL
Listed location countries
Age
Inclusion criteria
General inclusion criteria:
- Caucasian
- Male and female
- Ages 18 - 70 years
- Generally healthy
- Stable dietary habits (no weight loss/gain > 5 kg in the last 3 months),
Group 1 and 2, normal weight to overweight/obese healthy control participants:
- BMI > 18 and BMI < 35 kg/m2
- No medication use that interferes with our research parameters.
- Sedentary lifestyle
- VO2max < 30 for women and VO2max < 40ml/kg/min for men, Group 3, endurance
trained athletes:
- BMI < 25 kg/m2
- No family history of diabetes
- No medication use that interferes with our research parameters.
- VO2max > 60ml/kg/min for males and VO2max > 45ml/kg/min for females
- Active in endurance-exercise activities, 3 times a week for at least 2 years
- Stable level of training for at least 3 months
Exclusion criteria
- Regular smoking (in the last year)
- Previously diagnosed with type 2 diabetes
- Alcohol consumption (men> 30g/d; women > 20g/d)
- Medication use known to interfere with study parameters
- Use of anti-coagulants (not thrombocyte-aggregation inhibitors) or other
medication known to hamper blood coagulation.
- Weight gain/loss > 5 kg in the last 3 months
- Contraindications for MRI scans
- Participation in other studies within 1 month before the start of this study.
- Participants, who do not want to be informed about unexpected medical
findings, or do not wish that their physician be informed, cannot participate
in the study.
- Any condition, disease or abnormal laboratory test result that, in the
opinion of the investigator and the dependent physician, would interfere with
the study outcome, affect trial participation or put the subject at undue risk.
- Medication will be looked into per individual participant whether it
interferes with the study outcome, affect trial participation or put the
subject at undue risk, with special attention to the following medication:
o Selective serotonin re-uptake inhibitors
o Antipsychotics
o Anticonvulsants
o Thiazide diuretics
o Beta-blockers
o Corticosteroids
o Levotyroxine
o GnRH agonists
o Nicotinic acid
o Protease inhibitor
o Fibrates
o NSIADs
o Anticoagulants
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 | NL61390.068.17 |