To characterize phenotypical parameters, cytokine production and epigenetic characteristics of monocytes in patients with diabetes mellitus type 2, stratified according to antidiabetic treatment regime. Ex vivo exploration of the conditions which…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
We will compare monocyte expression of pro-atherogenic markers, cytokine
production, epigenetic changes and trans-endothelial migration between diabetes
patients and controls, and asses differences between patient groups.
Furthermore, changes in these parameters after ex vivo incubation with stimuli
and current and novel anti-inflammatory therapies will be assessed.
Secondary outcome
N.A.
Background summary
Patients with diabetes mellitus have an over tenfold lifetime risk for
cardiovascular (CV) disease. Chronic inflammation plays a key role in the
pathogenesis of atherosclerotic CV disease and transduces many of the CV risk
factors. Previous studies have appropriated a central role for monocytes, which
may exhibit prolonged pro-inflammatory phenotypes due to epigenetic
reprogramming mediated by hyperlipidemia. Similar epigenetically mediated
pro-inflammatory effects are thought to occur in patients with diabetes,
providing specific targets for novel anti-inflammatory therapies. However,
research addressing these changes in this heterogeneous group is lacking.
Study objective
To characterize phenotypical parameters, cytokine production and epigenetic
characteristics of monocytes in patients with diabetes mellitus type 2,
stratified according to antidiabetic treatment regime. Ex vivo exploration of
the conditions which lead to the pro-inflammatory activation of monocytes and
examination of its reversibility by current and novel anti-inflammatory
treatment options.
Study design
This study is designed as a single centre observational study. After screening
for eligibility, all subjects will undergo cardiovascular risk assessment and
laboratory testing. Monocyte phenotype (flow cytometry, gene expression and
protein expression) as well as functionality (cytokine production,
trans-endothelial migration) and epigenetic changes (methylation / acetylation
markers) will be analysed. The effect of ex vivo anti-inflammatory treatment on
these parameters will be assessed.
Study burden and risks
The burden and risks of participating in this study are estimated to be low.
The amount of visits will be limited to a maximum of two, in which patients
will undergo standard cardiovascular risk assessment once, with a maximal blood
withdrawal of 82 ml per visit.
Meibergdreef 9
Amsterdam Zuid Oost 1105 AZ
NL
Meibergdreef 9
Amsterdam Zuid Oost 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Patients
- Aged 18 years or older
- Diagnosed with diabetes mellitus type 2 ;Control subjects
- Age 18 years or older
- No history of diabetes mellitus or impaired glucose tolerance
- No history of cardiovascular events
- No medication use
Exclusion criteria
Exclusion criteria for all subjects
- Known malignant disorders or any clinically significant medical condition that could interfere with the conduct of the study in the opinion of the investigator.
- Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study.
- History of cardiovascular event within the last 3 months.
- Clinical signs of acute infection and/or CRP > 10 mg/L.
- The use of chronic immunosuppressant drugs or antibiotics in the last 6 weeks.
- Chronic use of anti-inflammatory drugs.
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 | NL63927.018.17 |