PBMC as Biomarkers of Diabetic Cardiomyopathy

Official title

Use of Peripheral Blood Mononuclear Cells as biOmarkers of diaBetic cardIomyopathy

Overview

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.

Interventions

• Biological Blood test
  During the routine blood test of the patient, 4 more tubes of 4 milliliters (mL) will be collected to make a biological collection of PBMC and plasma for further analysis.
• Behavioral quality of life Questionnaire
  During the routine medical visit, the patient will be asked to fill in a short questionnaire about quality of life. This is a descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. This decision results into a 1-digit number that expresses the level selected for that dimension. Each patient's health state is referred to in terms of a
• Behavioral Diet habits questionnaire
  During the routine medical visit, the patient will be asked to fill in a short questionnaire about his diet habits. This is an exploratory questionnaire that describes and quantifies the foods (pro- or anti-inflammatory) ingested by patients.

Primary outcome measures

• Comparison of Initial level of Ca2+ fluxes from T2D+MS patients vs non T2D+MS patients, according to the presence or not of HFpEF or HFmrEF [Time frame: Day of blood sample (inclusion visit)]
• Comparison of amplitude of Ca2+ fluxes from T2D+MS patients vs non T2D+MS patients, according to the presence or not of HFpEF or HFmrEF [Time frame: Day of blood sample (inclusion visit)]
• Comparison of area under curve of Ca2+ fluxes from T2D+MS patients vs non T2D+MS patients, according to the presence or not of HFpEF or HFmrEF [Time frame: Day of blood sample (inclusion visit)]
• Comparison of slope of the response to pharmacological stimulation of Ca2+ fluxes from T2D+MS patients vs non T2D+MS patients, according to the presence or not of HFpEF or HFmrEF [Time frame: Day of blood sample (inclusion visit)]
• Comparison of the inflammatory profile of PBMC from T2D+MS patients vs non T2D+MS patients, according to the presence or not of HFpEF or HFmrEF [Time frame: Day of blood sample (inclusion visit)]

Eligibility criteria

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%

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-control

Study locations

France · 1 center

• Hopital Louis Pradel — Bron

Identifiers

NCT: NCT05651919 · 69HCL22_0580 · 2022-A02435-38

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗