Targeting Glutamine Metabolism to Prevent Diabetic Cardiovascular Complications

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.

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