Diabetes
Conditions
Keywords
glutamine, cardiovascular
Brief summary
Diabetes and related complications, particularly cardiovascular disease, are associated to exacerbated inflammation, which is characterized by an activation into a pro-inflammatory status of myeloid cells including blood monocytes and tissue macrophages. It is known that monocytes and macrophages sense, integrate and respond to their microenvironment and continually monitor the availability of nutrients in order to adapt their activity and metabolism accordingly. However, the molecular mechanisms driving their activation and switch to a pro-inflammatory phenotype in diabetes are not fully elucidated. The Tricarboxylic Acid cycle is a nexus for multiple nutrient inputs and the generation of Tricarboxylic Acid cycle metabolites is nowadays thought to orient macrophage polarization. Reduced glutamine concentrations have been reported in patients with type 2 diabetes compared to healthy individuals. Ex vivo studies (mainly performed in rodent models) have shown that glutamine catabolism (glutaminolysis) is involved in the activation of macrophages by generating Tricarboxylic Acid cycle intermediates that promote the pro-inflammatory polarization of macrophages. Yet, the link - glutamine catabolism, monocytes polarization and diabetes-related cardiovascular complications - remains unclear. The first phase of this project (GlutaDiab) aimed to clarify this association by quantifying glutamine metabolism in serum and monocytes activation of type 1 and type 2 diabetic patients and investigating the possible correlation with the risk of cardiovascular complications in a transversal cohort. The GlutaDiab2 is the second phase of this project and aims to further investigate the association between glutamine metabolism and cardiovascular risk by collecting follow-up data on cardiovascular events. This longitudinal data will also address the directionality of the association between glutamine metabolism, monocytes activation and cardiovascular risk.
Detailed description
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 10 tubes (total: 53,5 mL) at a single time during the study
Interventions
BIOLOGICALblood sampling
A unique venous blood sampling of 10 tubes: 4 x 7 mL EDTA tubes + 3 x 5 mL EDTA tubes + 2 x 4 mL no additive tubes + 1x 2,5 mL Paxgene tube (total: 53,5 mL) at a single time during the study
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Person previously enroled in the GLUTADIAB study in group 1 or 2 (cf appendix 1 for GLUTADIAB inclusion criteria)
Exclusion criteria
* Pregnant or breastfeeding woman * Absence of free and informed consent * Subject deprived of freedom, subject under a legal protective measure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The main objective of the study is to compare the plasma concentrations of glutamine in patients at the first visit (baseline) and the risk of cardiovascular events occurring until the GlutaDiab2 visit | inclusion | The primary endpoint is the association between plasma concentration of glutamine in each subject and cardiovascular events occurring during follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To study cardiovascular events during follow-up according to glutamine metabolism in patients at baseline | inclusion | For the analysis of study cardiovascular events during follow-up according to glutamine metabolism in patients at baseline: First occurrence of a cardiovascular events according to the plasma concentration of glutamate in each treatment group |
| To study cardiovascular events during follow-up according to the inflammatory status in patients at baseline | inclusion | For the analysis of the cardiovascular events during follow-up according to the inflammatory status in patients at baseline: First occurrence of a cardiovascular events according to the plasma concentration of VEGF (vascular endothelial growth factor) in each treatment group |
| To study cardiovascular events during follow-up according to the monocyte activation status in patients at baseline | inclusion | First occurrence of a cardiovascular events according to the frequency of monocyte subsets |
| To study glutamine metabolism variations between baseline and follow-up visit according to variation in cardiovascular risk | inclusion | To study glutamine metabolism variations between baseline and follow-up visit according to variation in cardiovascular risk In participants without cardiovascular events occurring during follow-up, cardiovascular risk will be assessed through clinical and biological data and coronary artery calcium score |
Countries
France
Contacts
CONTACTAnnabelle METOIS
STUDY_CHAIRLouis POTIER
Bichat Hospital
Outcome results
None listed