Clinical trial NCT04353869: Targeting Glutamine Metabolism to Prevent Diabetic Cardiovascular Complications
Official title: Targeting Glutamine Metabolism to Prevent Diabetic Cardiovascular Complications
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Glutamine
Diabetic
Cardiovascular Complications
Keywords: Diabetes
Cardiovascular complications
Glutamine metabolism
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: National Research Agency, France
First posted: 2020-04-21
Enrollment: 995
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Adult Type 1 and 2 diabetic patients and non-diabetic subjects with various levels of cardiovascular risk

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.

Eligibility criteria: Inclusion criteria General inclusion criteria applying to the five populations are the following:

* Age above 18 years
* BMI between 25 and 40 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
* 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)

Group 2: Patients with uncomplicated diabetes and high cardiovascular risk, additional inclusion criteria are:

* 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)

Group 3: Patients with complicated diabetes, additional inclusion criteria are:

* 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

Primary outcomes:
measure: Compare the plasma concentrations of glutamine in patients with various levels of cardiovascular (CV) risk.
timeFrame: DAY 1
Secondary outcomes:
measure: Study glutamine metabolism in patients with various levels of CV risk
timeFrame: DAY 1
measure: Study glutamine metabolism in patients with various levels of CV risk
timeFrame: DAY1
measure: Study glutamine metabolism in patients with various levels of CV risk
timeFrame: DAY 1
measure: study the inflammatory status in patients with various levels of CV risk
timeFrame: DAY 1
measure: study the inflammatory status in patients with various levels of CV risk
timeFrame: DAY 1
measure: study the inflammatory status in patients with various levels of CV risk
timeFrame: DAY 1
measure: study the monocyte activation status in patients with various levels of CV risk
timeFrame: DAY 1
measure: 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
timeFrame: DAY 1
measure: 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
timeFrame: DAY 1
measure: 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
timeFrame: DAY 1
Other outcomes:
Locations:
city: Paris
country: France
facility: Diabétologie - Hôpital Lariboisière
city: Paris
country: France
facility: Diabetologie Bichat
Study officials:
References: