Targeting Glutamine Metabolism to Prevent Diabetic Cardiovascular Complications
Sleutelwoorden
Abstract
Omschrijving
The aim of the study is to investigate the role of glutamine metabolism in the pro-inflammatory activation of macrophages in diabetes and related cardiovascular complications.
The study focuses on 5 adult patients' population with different diabetic status and level of cardiovascular risk:
- Patients with uncomplicated type 1 or type 2 diabetes and low cardiovascular risk
- Patients with uncomplicated type 1 or type 2 diabetes and high cardiovascular risk
- Patients with complicated type 1 or type 2 diabetes
- Patients without diabetes and with a high cardiovascular risk
- Patients without diabetes and with a history of cardiovascular event
Participants (n=1650) will be recruited at clinical sites, in the diabetes and cardiology departments (APHP, Bichat - Claude-Bernard Hospital and APHP, Lariboisière Hospital), over a 2-year period.
The study will consist in a single visit. During a scheduled hospitalization or consultation as part of the follow-up of their diabetes or as part of the follow-up of their cardiological problems, clinical data will be collected as well as additional blood and urine samples for analyses and biobanking. There will be no other intervention specific to the study.
Datums
| Laatst geverifieerd: | 12/31/2019 |
| Eerste ingediend: | 04/15/2020 |
| Geschatte inschrijving ingediend: | 04/15/2020 |
| Eerst geplaatst: | 04/20/2020 |
| Laatste update ingediend: | 04/22/2020 |
| Laatste update geplaatst: | 04/26/2020 |
| Werkelijke startdatum van het onderzoek: | 06/29/2020 |
| Geschatte primaire voltooiingsdatum: | 06/29/2022 |
| Geschatte voltooiingsdatum van het onderzoek: | 12/29/2022 |
Conditie of ziekte
Interventie / behandeling
Biological: Bio collection
Fase
Armgroepen
| Arm | Interventie / behandeling |
|---|---|
| Group 1 Patients with uncomplicated diabetes and low cardiovascular risk
During a scheduled hospitalization or consultation as part of the follow-up of their diabetes additions of biological samples, which include:
A unique venous blood sampling of 9 tubes: 4 x 7 mL EDTA (Éthylènediaminetétraacétique) tubes + 3 x 5 mL EDTA tubes + 2 x 4 mL no additive tubes (total: 51 mL) at a single time during the study and collection of 2 monovettes of 1.6 ml urine (total: 3.2 mL). | |
| Group 2 Patients with uncomplicated diabetes and high cardiovascular risk
During a scheduled hospitalization or consultation as part of the follow-up of their diabetes additions of biological samples, which include:
A unique venous blood sampling of 9 tubes: 4 x 7 mL EDTA tubes + 3 x 5 mL EDTA tubes + 2 x 4 mL no additive tubes (total: 51 mL) at a single time during the study and collection of 2 monovettes of 1.6 ml urine (total: 3.2 mL). | |
| Group 3 Patients with complicated diabetes
During a scheduled hospitalization or consultation as part of the follow-up of their diabetes additions of biological samples, which include:
A unique venous blood sampling of 9 tubes: 4 x 7 mL EDTA tubes + 3 x 5 mL EDTA tubes + 2 x 4 mL no additive tubes (total: 51 mL) at a single time during the study and collection of 2 monovettes of 1.6 ml urine (total: 3.2 mL). | |
| Group 4 Patients without diabetes and with a high cardiovascular risk
Practical implementation During a scheduled hospitalization or consultation as part of the follow-up of their cardiological problems, additions of biological samples, which include:
A unique venous blood sampling of 9 tubes: 4 x 7 mL EDTA tubes + 3 x 5 mL EDTA tubes + 2 x 4 mL no additive tubes (total: 51 mL) at a single time during the study and collection of 2 monovettes of 1.6 ml urine (total: 3.2 mL). | |
| Group 5 Patients without diabetes and with a history of cardiovascular event
Practical implementation During a scheduled hospitalization or consultation as part of the follow-up of their cardiological problems, additions of biological samples, which include:
A unique venous blood sampling of 9 tubes: 4 x 7 mL EDTA tubes + 3 x 5 mL EDTA tubes + 2 x 4 mL no additive tubes (total: 51 mL) at a single time during the study and collection of 2 monovettes of 1.6 ml urine (total: 3.2 mL). |
Geschiktheidscriteria
| Leeftijden die in aanmerking komen voor studie | 18 Years Naar 18 Years |
| Geslachten die in aanmerking komen voor studie | All |
| Bemonsteringsmethode | Probability Sample |
| Accepteert gezonde vrijwilligers | Ja |
| Criteria | Inclusion criteria General inclusion criteria applying to the five populations are the following: - Age above 18 years - BMI between 25 and 35 kg/m² Inclusion criteria according to study group are listed below. Group 1: Patients with uncomplicated diabetes and low cardiovascular risk, additional inclusion criteria are: - 5 or more years of diabetes - 7% < HbA1c < 9% - No history of cardiovascular event, diabetic microvascular complications (normal kidney function and albuminuria/creatininuria < 30 mg/g) except background of non-proliferative moderate retinopathy - Coronary artery calcium score < 100 (assessment < 12 months) Group 2: Patients with uncomplicated diabetes and high cardiovascular risk, additional inclusion criteria are: - 5 or more years of diabetes - 7% < HbA1c < 9% - No history of cardiovascular event, diabetic microvascular complications (normal kidney function and albuminuria/creatininuria < 30 mg/g) except background of non-proliferative moderate retinopathy. - Coronary artery calcium score > 400 (assessment < 12 months) Group 3: Patients with complicated diabetes, additional inclusion criteria are: - 5 or more years of diabetes - 7% < HbA1c < 9% - A history of cardiovascular event (myocardial infarction, stroke, peripheral vascular disease, or angioplasty) at least 3 months ago Group 4: Patients without diabetes and with a high cardiovascular risk, additional inclusion criteria are: - Fasting glycemia < 1,26 g/l - No history of cardiovascular event (myocardial infarction, stroke, peripheral vascular disease, or angioplasty) - A coronary artery calcium score >400, (assessment < 12 months) Group 5: Patients without diabetes and with a history of cardiovascular event, additional inclusion criteria are: - Fasting glycemia < 1,26 g/l - A history of cardiovascular event (myocardial infarction, stroke, peripheral vascular disease, or angioplasty) at least 3 months ago Exclusion Criteria: - - Pregnant or breastfeeding woman - Absence of free and informed consent - Non-affiliation to a social security regimen or CMU (universal health coverage) - Subject deprived of freedom, subject under a legal protective measure |
Resultaat
Primaire uitkomstmaten
1. Compare the plasma concentrations of glutamine in patients with various levels of cardiovascular (CV) risk. [DAY 1]
Secundaire uitkomstmaten
1. Study glutamine metabolism in patients with various levels of CV risk [DAY 1]
2. Study glutamine metabolism in patients with various levels of CV risk [DAY1]
3. Study glutamine metabolism in patients with various levels of CV risk [DAY 1]
4. study the inflammatory status in patients with various levels of CV risk [DAY 1]
5. study the inflammatory status in patients with various levels of CV risk [DAY 1]
6. study the inflammatory status in patients with various levels of CV risk [DAY 1]
7. study the monocyte activation status in patients with various levels of CV risk [DAY 1]
8. characterize the transcriptomic program through modification gene expression and epigenetic changes related to KDM6B (Lysine Demethylase 6B) and TET2 (Ten-eleven-translocation 2) activity in blood monocytes from patients with various levels of CV risk [DAY 1]
9. characterize the transcriptomic program through modification gene expression and epigenetic changes related to KDM6B and TET2 activity in blood monocytes from patients with various levels of CV risk [DAY 1]
10. characterize the transcriptomic program through modification gene expression and epigenetic changes related to KDM6B and TET2 activity in blood monocytes from patients with various levels of CV risk [DAY 1]
