Targeting Glutamine Metabolism to Prevent Diabetic Cardiovascular Complications

Completed

• Conditions: Diabetic; Glutamine; Cardiovascular Complications
• Interventions: Biological: Bio collection

• Registration Number: NCT04353869
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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

Detailed Description

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 Timeline

• Study First Submitted: 2020-04-16
• Study First Submitted QC: 2020-04-16
• Study First Posted: 2020-04-21
• Study Start: 2020-11-16
• Primary Completion: 2024-01-10
• Study Completion: 2024-01-10
• Status Verified: 2024-03
• Last Update Submitted: 2025-02-28
• Last Update Posted: 2025-03-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 995

Inclusion Criteria

Not provided

Exclusion Criteria

• Solid organ or bone marrow transplant patient
• 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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Group 2	Bio collection	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 1	Bio collection	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 3	Bio collection	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).

Primary Outcome Measures

Name	Time	Method
Compare the plasma concentrations of glutamine in patients with various levels of cardiovascular (CV) risk.	DAY 1	plasma concentration of glutamine in each subject.

Secondary Outcome Measures

Name	Time	Method
study the monocyte activation status in patients with various levels of CV risk	DAY 1	frequency of monocyte subsets (CD14++CD16+, CD14++CD16++, CD14+CD16++)
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	Number of transcript for each gene
study the inflammatory status in patients with various levels of CV risk	DAY 1	blood concentration of circulating PBMCs (peripheral blood mononuclear cell)
Study glutamine metabolism in patients with various levels of CV risk	DAY 1	monocyte cytoplasmic concentration of a-ketoglutarate, fumarate and succinate in each treatment group
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	Frequency and level of histone H3K27me (Methylation of lysine 27 on histone H3) methylation

Trial Locations

Locations (2)

Diabétologie - Hôpital Lariboisière; 🇫🇷 Paris, France

Diabetologie Bichat; 🇫🇷 Paris, France