To study nocturnal FFA rhythm with or without *-blockers in insulin resistant subjects and healthy controls.
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Percent and/or absolute changes in nocturnal FFA levels with or without *-
blockage.
2. Difference in nocturnal FFA levels between lean and obese subjects.
Secondary outcome
Phenotypical differences (adipose tissue distribution, plasma parameters)
Background summary
It has been convincingly demonstrated that free fatty acids (FFA) play a key
role in the induction of obesity-induced insulin resistance (3). The higher
plasma levels of FFA originate from adipocytes which show higher rates of
lipolysis in insulin stimulated states, i.e. insulin resistance of adipose
tissue. The release of FFA is pulsatile and show a circadian rhythm (4) and is
thereby in part controlled by the central nervous system. Whether this
pulsatility or rhythm is disturbed in insulin resistant subjects is not known.
In a dog model FFA levels can be lowered by blocking the *-receptor present on
the adipocyt, thereby decreasing the influence of the central nervous system on
FFA release. In this study we aim to translate these findings to obese insulin
resistant and lean insulin sensitive humans.
Study objective
To study nocturnal FFA rhythm with or without *-blockers in insulin resistant
subjects and healthy controls.
Study design
observational single blinded intervention study.
Intervention
Each subject will be studied twice in random assignment. They will receive
propranolol or saline intravenously for 12 hours during one night.
Study burden and risks
Subjects will visit the research unit twice. Each visit lasts 14 hours. On both
visits the subject will have to stay overnight during which blood will be taken
every ten minutes. Catheters will be placed in antecubital veins for blood
sampling (maximum volume for each visit 250 ml) and infusion of saline or
propranolol. Heart rate will be monitored every 30 minutes and the propranolol
infusion will be adapted when heart rate will drop under 50 beats per minute.
Meibergdreef 9
1105 AZ Amsterdam Zuidoost
Nederland
Meibergdreef 9
1105 AZ Amsterdam Zuidoost
Nederland
Listed location countries
Age
Inclusion criteria
Kaukasische man met een BMI > 30 kg/m2 of een BMI 20<25 kg.m2.
Exclusion criteria
* any chronic medical condition or use of any medication
* asthma and bronchospastic COPD
* tobacco use
* alcohol abuse (>3/day)
* frequent intensive exercise (>2 week)
* familial lipid disorders, renal insufficiency (creatinine > 150 umol/L) , elevated liver enzymes (> 2 times), hypertension
* Hypotension (BP < 100/60 mmHg), bradycardia (HR < 60min)
* unwilling or unable to provide informed consent
* first degree family members with diabetes
* abnormal day/night rhythm (shiftworkers etc)
* Blood donation in the past three months
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2008-006843-37-NL |
| CCMO | NL24949.018.08 |