To determine the effect of hypoglycaemia on BAT-activity.
ID
Source
Brief title
Condition
- Diabetic complications
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in Standardised Uptake Value (SUV) of the tracer
[18F]-fluorodeoxyglucose (FDG) visualised with positron emission tomography
(PET) in BAT (normoglycaemia vs. hypoglycaemia).
Secondary outcome
Difference between the change in SUV in BAT in the group with healthy
volunteers versus the diabetes patients.
Background summary
We hypothesise that there is a central mechanism that shuts down energy
consumption by brown adipose tissue (BAT) during hypoglycaemia. This could be a
mechanism to protect the brain from neuroglycopenia.
Study objective
To determine the effect of hypoglycaemia on BAT-activity.
Study design
Observational design. Two 18F-FDG PET-CT scans per patient will be performed of
the upper body half to visualise the activity of BAT.
The first scan will be performed following a hyperinsulinaemic normoglycaemic
clamp and the second scan will be performed following a hyperinsulinaemic
hypoglycaemic clamp (separated from the first scan by at least 2 weeks).
Intervention
The first scan will be performed following a hyperinsulinaemic normoglycaemic
clamp and the second scan will be performed following a hyperinsulinaemic
hypoglycaemic clamp (separated from the first scan by at least 2 weeks).
Study burden and risks
Included subjects will visit the AMC hospital on three occasions.
Visit 1: informed consent, medical history, vital signs, explanation of study
procedures, laboratory measurements. Total blood drawn: 12.5 ml.
Visit 2: hyperinsulinaemic normoglycaemic clamp and subsequent [18F]FDG-PET scan
Visit 3: hyperinsulinaemic hypoglycaemic clamp and subsequent [18F]FDG-PET scan
At visit 2 and 3: subjects will be asked to come to the AMC in a fasting state.
In total 213.5 ml of blood will be drawn over the study.
Induction of hypoglycaemia can lead to severe hypoglycaemia with coma or
seizures. However, this normally does not occur with the arterialized blood
glucose values that are reached in this study. In case of adverse sequelae of
hypoglycaemia (e.g. coma, epileptic fit), insulin will be discontinued and
glucose will be infused until symptoms abate. The patients might develop
hypothermia when they stay in a cold room, especially in a situation with
hypoglycaemia. We will monitor the patient*s temperature with a tympanic
thermometer. In case a patient develops hypothermia the study will be
cancelled.The resulting dose from the low-dose CT scan and the injected
radioactive tracer is approximately 9.4 mSv. This is classified as an
intermediate risk (ICRP62).
There is no direct benefit for the volunteers. The study will provide new
physiologic insight in a possible central pathway influencing BAT activity and
the effect of diabetes itself on BAT activity and therefore also on temperature
regulation and metabolism. This knowledge might be useful in developing
strategies to prevent hypoglycaemia and its consequences in insulin treated
diabetes. Moreover, insight in the regulatory mechanisms of BAT activity may
help to find a way to increase energy expenditure and prevent/treat obesity.
Postbus 22660
1100DD
NL
Postbus 22660
1100DD
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria for healthy volunteers
* Male
* Caucasian race
* 18-50 years old
* BMI 20-28 kg/ m2
* Subjects should be able and willing to give informed consent;Inclusion criteria for type 1 diabetes patients
* Male
* Caucasian race
* Age 18-50 years
* BMI 20-28 kg/ m2
* Type 1 Diabetes Mellitus
* Subjects should be able and willing to give informed consent
Exclusion criteria
Exclusion criteria for healthy volunteers
* Use of prescription medications (beta-adrenoreceptor blockers)
* Cardiac history (previous arrhythmia)
* History of epilepsy
* Acute illness within 3 months before the study
* Significant renal impairment (creatinine clearance <50ml/min)
* Family history of diabetes;Exclusion criteria for type 1 diabetes patients
* Impaired awareness of hypoglycaemia
* Evidence of severe diabetes complications (autonomic neuropathy, macroalbuminuria, proliferative retinopathy)
* Use of beta-adrenoreceptor blockers
* Cardiac history (previous arrhythmia)
* History of epilepsy
* Acute illness within 3 months before the study
* Significant renal impairment (creatinine clearance <50ml/min)
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 | NL34584.018.10 |