Activation Innate Immune System in Type 1 Diabetes
Activation of the Innate Immune System and Vascular Inflammation in Patients With Type 1 Diabetes
1 other identifier
observational
66
1 country
1
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for all trials
Started Jan 2018
Shorter than P25 for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 18, 2018
CompletedFirst Submitted
Initial submission to the registry
January 22, 2018
CompletedFirst Posted
Study publicly available on registry
February 22, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 21, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
January 21, 2019
CompletedApril 2, 2019
March 1, 2019
1 year
January 22, 2018
March 29, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Arterial wall inflammation, measured by 18F-FDG-PET/CT
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.
through study completion, within 1 year
Secondary Outcomes (5)
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
Study Arms (3)
Patients with type 1 diabetes, poor glycemic control
* Diagnosis based on clinical criteria * Duration of diabetes ≥10 years * Age ≥20 years, ≤ 60 years * HbA1c \>64 mmol/mol
Patients with type 1 diabetes, good glycemic control
* Diagnosis based on clinical criteria * Duration of diabetes ≥10 years * Age ≥20 years, ≤ 60 years * HbA1c \<64 mmol/mol
Healthy subjects
* Absence of disease, no use of medication * Matched for age, gender and BMI * HbA1c \<42 mmol/mol
Interventions
PET-CT to determine vascular inflammation
Blood drawn
Eligibility Criteria
Type 1 diabetes patients, without macrovascular complications. Minimum diabetes duration 10 years. Patients are recruited at university hospital.
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Radboud University Nijmegen Medical Centre, Department of Internal Medicine
Nijmegen, PO BOX 9101, 6500 HB, Netherlands
Related Publications (1)
Thiem K, van Dierendonck XAMH, Janssen AWM, Boogaard JP, Riksen NP, Tack CJ, Stienstra R. A High Glycemic Burden Relates to Functional and Metabolic Alterations of Human Monocytes in Patients With Type 1 Diabetes. Diabetes. 2020 Dec;69(12):2735-2746. doi: 10.2337/db20-0568. Epub 2020 Sep 25.
PMID: 32978233DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- observational
- Observational Model
- CASE CONTROL
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 22, 2018
First Posted
February 22, 2018
Study Start
January 18, 2018
Primary Completion
January 21, 2019
Study Completion
January 21, 2019
Last Updated
April 2, 2019
Record last verified: 2019-03