Targeting Glutamine Metabolism to Prevent Diabetic Cardiovascular Complications

NCT ID: NCT04353869

Last Updated: 2025-03-05

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 995 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-11-16
• Study Completion Date: 2024-01-10

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.

Conditions

Glutamine; Diabetic; Cardiovascular Complications

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

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).

Bio collection

Intervention Type: BIOLOGICAL

venous blood sampling and collection of urine

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).

Bio collection

Intervention Type: BIOLOGICAL

venous blood sampling and collection of urine

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).

Bio collection

Intervention Type: BIOLOGICAL

venous blood sampling and collection of urine

Interventions

Bio collection

venous blood sampling and collection of urine

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Age above 18 years
• BMI between 25 and 40 kg/m²

• 5 or more years of diabetes
• 6% < HbA1c < 10%
• no history of cardiovascular event, diabetic microvascular complications (kidney function normal and albuminuria/creatininuria < 30 mg/g)
• Coronary artery calcium score < 100 (assessment < 12 months)

• 5 or more years of diabetes
• 6% < HbA1c < 10%
• no history of cardiovascular eventand diabetic nephropathy no more than stage 2 (i.e. GFR ≥ 60 ml/min by MDRD or CKD-EPI formula and albuminuria/creatininuria ≤ 30 mg/g)
• Coronary artery calcium score > 400 (assessment < 12 months)

• 5 or more years of diabetes
• 6% < HbA1c < 10%
• A history of cardiovascular event (myocardial infarction, stroke, peripheral vascular disease, or angioplasty) at least 3 months ago

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Research Agency, France

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Diabétologie - Hôpital Lariboisière

Paris, France, France

Diabetologie Bichat

Paris, France, France

Countries

France

References

Julla JB, Girard D, Diedisheim M, Saulnier PJ, Tran Vuong B, Bleriot C, Carcarino E, De Keizer J, Orliaguet L, Nemazanyy I, Potier C, Khider K, Tonui DC, Ejlalmanesh T, Ballaire R, Mambu Mambueni H, Germain S, Gaborit B, Vidal-Trecan T, Riveline JP, Garchon HJ, Fenaille F, Lemoine S, Carlier A, Castelli F, Potier L, Masson D, Roussel R, Vandiedonck C, Hadjadj S, Alzaid F, Gautier JF, Venteclef N. Blood Monocyte Phenotype Is A Marker of Cardiovascular Risk in Type 2 Diabetes. Circ Res. 2024 Jan 19;134(2):189-202. doi: 10.1161/CIRCRESAHA.123.322757. Epub 2023 Dec 28.

Reference Type: DERIVED

PMID: 38152893 (View on PubMed)

Other Identifiers

GLUTADIAB

Identifier Type: -

Identifier Source: org_study_id