Activation of the Innate Immune System and Vascular Inflammation in Patients With Type 1 Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Arterial wall inflammation, measured by 18F-FDG-PET/CT
研究概览
简要总结
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.
The investigators 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, the investigators 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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 20 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Group 1 and 2 (patients with type 1 diabetes):
- •Diagnosis based on clinical criteria
- •Duration of diabetes ≥10 years
- •Age ≥20 years, ≤ 60 years
- •Group 1: HbA1c >64 mmol/mol
- •Group 2: HbA1c ≤64 mmol/mol
- •Written informed consent
- •Group 3 (healthy controls):
- •Absence of disease, no use of medication
- •Matched for age, gender and BMI
- •HbA1c <42 mmol/mol
- •Written informed consent
排除标准
- •Inability to provide informed consent
- •Specific Medication use:
- •Use of immunosuppressive drugs
- •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.)
- •Use of acetylsalicylic acid
- •Previous cardiovascular events (ischemic stroke/TIA (transient ischemic attack), 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
结局指标
主要结局
Arterial wall inflammation, measured by 18F-FDG-PET/CT
时间窗: through study completion, within 1 year
Compare arterial wall inflammation (expressed as target-to-background-ratio (TBR) measured in large arterial vessels) between well- and poorly-controlled patients. The TBR is the ratio of FDG uptake in large arterial and large venous bloodvessels.
次要结局
- FDG (fluorodeoxyglucose) uptake in spleen and bone marrow, measured by 18F-FDG-PET/CT.(through study completion, within 1 year)
- Inflammatory phenotype(Most measurements within 1 week after inclusion. Cytokine measurements after completion of the inclusion of all patients.)
- Intracellular metabolism, measured by Seahorse respirometer(within 1 day after inclusion)
- Epigenetic changes(Within 2 months after inclusion)
- Arterial wall inflammation, measured by 18F-FDG-PET/CT(through study completion, within 1 year)