The primary objectives of this study are: (1) To establish the role of brown adipose tissue in cold-induced thermogenesis before and after a cold acclimation period; (2) to study the involvement of skeletal muscle mitochondrial uncoupling in cold-…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
type 2 diabetes en overgewicht
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. To establish the role of brown adipose tissue in cold-induced thermogenesis
before and after a cold acclimation period
2. To study the involvement of skeletal muscle mitochondrial uncoupling in
cold-induced thermogenesis
3. To study the effect of chronic cold exposure on the white adipose tissue
depot
Secondary outcome
1. To study the effect of short-term and chronic cold exposure on relevant
blood parameters
2. To establish the effect of short-term and chronic cold exposure on body
temperatures and skin temperatures
3. To establish the role of polymorphisms in the UCP-1 and beta-3 receptor gene
on BAT activity and cold-induced thermogenesis.
Background summary
Upon mild cold exposure people can increase their energy expenditure. This is
called non-shivering thermogenesis (NST). Moreover, during prolonged cold
exposure NST can increase, this is called adaptive thermogenesis (AT). This
metabolic reaction is subject to high inter-individual variability. These
differences might be explained by the amount of active brown adipose tissue
(BAT). Furthermore, a negative correlation between BAT activity and BMI was
found and obese people show an impaired cold-induced thermogenesis. In
addition, diabetic status has been associated independently with reduced BAT
activity. In rodents, BAT and the skeletal muscle are mainly responsible for
NST, and upon chronic cold exposure recruitment of BAT takes place. Recently,
we showed that severe weight loss in obese subjects causes BAT recruitment, and
BAT activity correlates with NST. Moreover, white fat cells can be converted
into brown-like cells, called BRITE cell recruitment. Chronic cold exposure in
healthy men showed a decrease in shivering with remaining elevated energy
expenditure; this indicates that humans are also capable to increase NST.
It is hypothesized that upon chronic cold exposure in healthy obese adults,
with or without type 2 diabetes, BAT and BRITE recruitment will take place.
Furthermore, skeletal muscle mitochondrial uncoupling and adaptive
thermogenesis will increase.
Study objective
The primary objectives of this study are: (1) To establish the role of brown
adipose tissue in cold-induced thermogenesis before and after a cold
acclimation period; (2) to study the involvement of skeletal muscle
mitochondrial uncoupling in cold-induced thermogenesis and (3) to study the
effect of chronic cold exposure on the white adipose tissue depot.
Study design
The volunteers will undergo two PET/CT-scans, in which cold-induced BAT
activity will be measured before and after a cold acclimation period of 10
days. To investigate the role of the skeletal muscle mitochondrial uncoupling
and BRITE cell recruitment a muscle and fat biopsy sample will be taken prior
to the acclimation period and afterwards.
Intervention
Cold exposure. For 10 consecutive days the subjects will be exposed to cold (12
C).
To easily get used to this, exposure will be 2hours at the 1st day, 4hours at
the 2nd day and day 3-10 6hours/day.
Study burden and risks
The risks of this study are low.
The total effective dose is low and will not give any risk to the subjects
The total absorbed radiation dose from two FDG-PET/CT-scans after
administration of two times 75 MBq of 18F-FDG
is 4.6 mSv.
This is about three times the background radiation in the Netherlands and is
below the criteria as stated in ICRP-60,
<10 mSv.
St. Annalaan 9B7
Maastricht 6214 AA
NL
St. Annalaan 9B7
Maastricht 6214 AA
NL
Listed location countries
Age
Inclusion criteria
* Caucasians
* Age:
o Obese without type 2 diabetes: 18-65 years
o Obese with type 2 diabetes: 18-65 years
* BMI: 28-35 kg/m2
* Fat percentage: > 23%
* Gender: Male
* Specifically for obese subjects with type 2 diabetics:
o Diagnosed with type 2 diabetes at least 1.5 years before the start of the study
o Well-controlled type 2 diabetes: HBA1C < 8.5%
o Oral glucose lowering medication (metformin only or in combination with sulfonylurea agents)
o No signs of active diabetes-related co-morbidities like cardiovascular diseases, diabetic foot, polyneuropathy, retinopathy.
o No signs of active uncontrolled hypertension, liver of kidney malfunction
* Specifically for obese subjects without type 2 diabetes:
o Fasting blood glucose level <6.1 mmol/l
o No signs of active cardiovascular disease, uncontrolled hypertension, liver of kidney malfunction.
Exclusion criteria
* Participate in physical activity more than 2x/week
* Participation in earlier research that included a PET/CT-scan
* Radiation therapy due to medical treatment
* Unstable body weight (weight gain or loss > 5 kg in the last three months)
* Participation in another biomedical study within 1 month before the first screening visit;* Specifically for obese subjects without type 2 diabetes:
o Elevated fasting blood glucose level (> 6.1 mmol/L);* Specifically for obese subjects with type 2 diabetes:
o Impaired kidney- and/or hepatic function
o Diabetes related co-morbidities like cardiovascular diseases, diabetic foot, polyneuropathy, and retinopathy.
o Insulin dependent diabetic subjects
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 | NL45645.068.13 |