PBMC as Biomarkers of Diabetic Cardiomyopathy

Use of Peripheral Blood Mononuclear Cells as biOmarkers of diaBetic cardIomyopathy

Type 2 diabetes (T2D), especially when associated with metabolic syndrome (MS) is at high risk to develop heart failure with preserved ejection fraction (HFpEF) or heart failure with mildly reduced ejection fraction (HFmrEF), and the specific impact of T2D+MS in cardiac function impairment is usually known as "diabetic cardiomyopathy" (DC). Cardiac remodelling (ie hypertrophy) and subtle myocardial dysfunction are highly prevalent in T2D+MS but not specific enough to predict further HFpEF or HFmrEF. Also, current biomarkers can identify but do not predict HFpEF or HFmrEF in T2D patients; Furthermore, specific biomarkers are needed. Peripheral blood mononuclear cells (PBMC) obtained from a peripheral blood sample can provide insights from calcic and inflammatory pathways, and may identify more specific molecular signatures shared between T2D+MS and HFpEF.

Inclusion Criteria:

Inclusion criteria common to the 4 groups:

• Patient attending a scheduled cardiology or endocrinology follow-up visit
• Patient fasting for blood sampling
• Male or female aged 40 to 85 years inclusive
• Patient not opposing participation in this research
• Patient agreeing to the storage of biological samples and to genetic analyses

Group 1: No-T2D +MS / No-HF (control group)

- Patient without T2D or MS and without heart failure coming to a consultation or day hospital for another reason (e.g. screening for atypical symptom, etc.)

Group 2: No-T2D +MS / HFpEF or HFmrEF

• Patient without T2D or MS
• HFpEF or HFmrEF. diagnosed

Group 3: T2D+MS / no-HF

• Patient diagnosed with T2D+MS
• - Absence of HF

Group 4: T2D +MS / HFpEF or HFmrEF

• Patient diagnosed with T2D and MS
• HFpEF or HFmrEF. diagnosed

Exclusion Criteria:

Non-inclusion criteria common to the 4 groups:

• History of cardiovascular disease (valvular disease [greater than moderate severity], radiation-induced, post-cardiotoxic chemotherapy, amyloidosis, etc.) other than HFpEF or HFmrEF
• Acute or ongoing systemic inflammatory or infectious disease
• History of known coronary artery disease
• Uncontrolled hypertension (>160/100 mmHg)
• Pregnant or breastfeeding women (based on interview)
• Persons deprived of liberty by judicial or administrative decision
• Persons undergoing psychiatric care
• Patient under legal protection (guardianship or curatorship)
• Subject participating in another interventional study with an ongoing exclusion period
• Chronic kidney disease (eGFR <30 mL/min/1.73 m²)

Group 1: No-T2D +MS / No-HF (control group)

• Presence of diabetes (whatever the type) and MS
• Presence of heart failure or other known heart disease

Group 2: No-T2D +MS / HFpEF or HFmrEF

• Presence of diabetes (whatever the type) and MS
• Left Ventricular Ejection Fraction (LVEF) on ultrasound ≤ 40%

Group 3: T2D+MS / no-HF

• Without diabetes or other type of diabetes than T2D
• Presence of Heart failure (all types)

Group 4: T2D +MS / HFpEF or HFmrEF

• Absence of diabetes or presence of another type of diabetes than T2D
• LVEF on ultrasound ≤ 40%