Experimental data suggest that glutamine catabolism in involved in the activation of macrophages by generating TCA(Tricarboxylic acid) intermediates that promote the pro-inflammatory polarization of macrophages. The project investigates the possible link between glutaminolysis, monocytes polarization and diabetes related cardiovascular complications in humans
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 3 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 Participants (n=975) 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.
Study Type
OBSERVATIONAL
Enrollment
995
venous blood sampling and collection of urine
Diabétologie - Hôpital Lariboisière
Paris, France, France
Diabetologie Bichat
Paris, France, France
Compare the plasma concentrations of glutamine in patients with various levels of cardiovascular (CV) risk.
plasma concentration of glutamine in each subject.
Time frame: DAY 1
Study glutamine metabolism in patients with various levels of CV risk
plasma concentration of glutamate in each treatment group
Time frame: DAY 1
Study glutamine metabolism in patients with various levels of CV risk
plasma concentration of a-ketoglutarate, fumarate, and succinate in each treatment group
Time frame: DAY1
Study glutamine metabolism in patients with various levels of CV risk
monocyte cytoplasmic concentration of a-ketoglutarate, fumarate and succinate in each treatment group
Time frame: DAY 1
study the inflammatory status in patients with various levels of CV risk
plasma concentration of VEGF (Vascular endothelial growth factor) in each treatment group
Time frame: DAY 1
study the inflammatory status in patients with various levels of CV risk
plasma concentration of the proinflammatory cytokines IL-1, IL-6, IL-8 (interleukin) and TNF-a (Tumor Necrosis Factor alpha)
Time frame: DAY 1
study the inflammatory status in patients with various levels of CV risk
blood concentration of circulating PBMCs (peripheral blood mononuclear cell)
Time frame: DAY 1
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study the monocyte activation status in patients with various levels of CV risk
frequency of monocyte subsets (CD14++CD16+, CD14++CD16++, CD14+CD16++)
Time frame: DAY 1
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
Number of transcript for each gene
Time frame: DAY 1
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
Number of methylated gene loci and their proportion of methylation
Time frame: DAY 1
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
Frequency and level of histone H3K27me (Methylation of lysine 27 on histone H3) methylation
Time frame: DAY 1