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.

Inclusion Criteria:

• 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

Exclusion Criteria:

• Inability to provide informed consent

• Smoking

• 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

Type 1 diabetes patients, without macrovascular complications. Minimum diabetes duration 10 years.

Patients are recruited at university hospital.