In this study we want to investigate whether the increased levels of RBP-4 are correlated to the expression levels in liver, skeletal muscle and adipose tissue. Also, we want to study the correlation between the levels of expression and glucose and…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Expression of RBP4 in liver, skeletal muscle and adipose tissue
Glucose production, glucose uptake and lipolysis
RBP-4 concentration in plasma
Secondary outcome
Correlation tissue levels of RBP4 and phosphorylation of insulin signaling
proteins
Background summary
The prevalence of obesity, insulin resistance and diabetes type 2 is increasing
worldwide and threatens human health. How obesity interferes with glucose
metabolism is not completely elucidated yet.
Recently, retinol binding protein-4 (RBP-4), derived from adipose tissue and
liver has been described to be elevated in plasma of obese insulin resistant
subjects. Also, it has been shown that insulin sensitivity is correlated
negatively to levels of circulating RBP-4. In studies with rodents, RBP-4
interfered directly with glucose uptake in muscle and with glucose production
in the liver. Whether this is also true for humans, is unknown.
Study objective
In this study we want to investigate whether the increased levels of RBP-4 are
correlated to the expression levels in liver, skeletal muscle and adipose
tissue. Also, we want to study the correlation between the levels of expression
and glucose and lipid fluxes.
Study design
We will study two groups of obese subjects scheduled for bariatric surgery, one
group with obese subjects who are metabolically healthy and one group who is
metabolically unhealthy. This will show whether RBP-4 is indeed important in
the induction of insulin resistance. We will also study differences in
expression levels of RBP-4 in subcutaneous adipose tissue, liver and skeletal
muscle between lean and obese subjects.
Intervention
Glucose fluxes will be measured during a hyperinsulinemic clamp using stable
isotopes. Biopsies of skeletal muscle and subcutaneous adipose tissue will be
performed during the clamp. Biopsies of the liver and intra abdominal fat from
subjects which will be operated will be taken during surgery.
Study burden and risks
The hyperinsulinemic clamp and the use of stable isotopes are safe.
Hypoglycemia during the clamp will be avoided by measuring plasma glucose
regularly. The risk of prolonged bleeding from the biopsies of muscle and
subcutaneous adipose tissue will be minimized by use of a pressure bandage and
manual external compression. The risk of bleeding from the liver and intra
abdominal fat biopsies will be reduced by checking local hemostasis during and
twice after the biopsy. If needed electrical coagulation will be performed.
Meibergdreef 9
1105 AZ Amsterdam
NL
Meibergdreef 9
1105 AZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
Lean subjects:
BMI 20-25 kg/m2 (stable weight)
Age between 20 and 60 years
Obese subjects:
- BMI > 30 kg/m2 for part one or > 35 kg/m2 for part two
- Age between 20 and 60 years
- HOMA-IR > 1.95 for part one
Exclusion criteria
Lean subjects:
any medical condition (except for gallstone formation) or use of medication
family history of diabetes mellitus type 2
performance of vigorous exercise
Obese subjects:
primary lipid disorder or secondary lipid disorder treated with fibrates
diabetes mellitus type 2 (DM2) treated with thiazolidinediones, DPP4-inhibitors or GLP1-analogues
any medical condition except for glucose intolerance, DM2, hypertension and secondary dyslipidemia
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 | NL29089.018.09 |