Primary Objective: 1. To determine whether there is a difference in arterial wall inflammation between well-controlled and poorly-controlled type 1 diabetes patients2. To determine whether patients with type 1 diabetes have a higher level of…
ID
Source
Brief title
Condition
- Diabetic complications
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Vascular wall inflammation in the aorta, left and right carotid artery and left
and right iliac and femoral arteries, as quantified by FDG-PET scanning.
Secondary outcome
FDG uptake in spleen and bone marrow.
Ex vivo determination of the inflammatory/atherogenic phenotype, cellular
metabolism of circulating monocytes and epigenetic signature of monocytes.
Background summary
Hyperglycemia is a well-known cardiovascular risk factor. It has also been
shown that episodes of hyperglycemia increase the risk for cardiovascular
diseases despite return to normoglycemia, a phenomenon termed 'glycemic or
metabolic memory'. The molecular mechanism underlying this phenomenon remains
unclear.
Cardiovascular events, such as myocardial infarction and stroke are caused by
atherosclerosis, which is characterized by low grade inflammation of the
vascular wall, including accumulation of innate immune cells such as monocytes
and macrophages.
We hypothesize that chronic hyperglycemia shifts intracellular metabolism of
innate immune cells towards glycolysis and changes the epigenetic state of
(progenitors of) innate immune cells (monocytes and macrophages), which
reprograms these cells towards a more aggressive, pro-atherogenic phenotype,
thereby accelerating atherosclerosis.
In this study, we aim to test this hypothesis. This research will reveal
whether the innate immune cells of patients with chronic hyperglycemia show a
durable shift in intracellular metabolism and epigenetic changes and whether
this associates with vascular inflammation.
Study objective
Primary Objective:
1. To determine whether there is a difference in arterial wall inflammation
between well-controlled and poorly-controlled type 1 diabetes patients
2. To determine whether patients with type 1 diabetes have a higher level of
arterial wall inflammation than patients without diabetes.
Secondary Objectives:
3. To determine whether poorly-controlled type 1 diabetes patients have an
increased FDG uptake in the bone marrow and spleen as compared to
well-controlled patients, and whether type 1 diabetes patients differ from
healthy controls with this respect.
4. To investigate whether circulating monocytes of patients with
poorly-controlled type 1 diabetes are characterized by a more pro-inflammatory
phenotype compared to well-controlled type 1 diabetes patients, and whether
there is a difference between type 1 diabetes patients and healthy controls.
5. To study whether there is a shift in intracellular metabolism in monocytes
of type 1 diabetes patients (well-controlled versus poorly-controlled patients)
compared to healthy controls.
6. To explore epigenetic changes in monocytes of type 1 diabetes patients
(well-controlled versus poorly-controlled patients) compared to healthy
controls.
Study design
Observational study in patients with type 1 diabetes (well-controlled versus
poorly-controlled patients) and healthy controls.
Study burden and risks
The risks associated with participation in this study are low. In total, 100 ml
blood will be obtained, which is not associated with relevant side effects. In
addition, all patients will undergo an 18FDG-PET/CT. This diagnostic procedure
will be performed according to standard state-of-the-art clinical procedures as
define by the European association of Nuclear Medicine. Duration of the
procedure: 3 hours. Procedure-related exposure to radioactivity: 5.0 mSv.
Patients will not have a direct benefit from participation in the study.
Geert Grooteplein 8
Nijmegen 6524 GA
NL
Geert Grooteplein 8
Nijmegen 6524 GA
NL
Listed location countries
Age
Inclusion criteria
Group 1: Type 1 diabetes, HbA1c > 64 mmol/mol; Group 2: Type 1 diabetes, HbA1c <64 mmol/l; Group 3: Healthy controls.
Group 1 and 2: type 1 diabetes, diagnosis based on clinical data, duration of diabetes *10 years, age *20 years, * 60 years, written informed consent
Group 3: absence of disease; matched for age,, gender and BMI; HbA1c <42 mmol/mol; written informed consent
Exclusion criteria
- Inability to provide informed consent
- Smoking
- Specific Medication use:
o Use of immunosuppressive drugs
o Use of statins < 2 weeks before performing PET-CT (Those that use statins will be asked to discontinue for two weeks. This can be safely done in the context of primary prevention.)
o Use of acetylsalicylic acid
- Previous cardiovascular events (ischemic stroke/TIA, myocardial infarction, peripheral arterial disease)
- Auto-inflammatory or auto-immune diseases
- Current or recent infection (< 3 months)
- Previous vaccination (< 3 months)
- Renal failure (MDRD <45)
- BMI>30 kg/m2
- Pregnancy
- Claustrophobia
- Severe hypoglycaemia < 1 week before PET-CT
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 | NL62200.091.17 |