Trancriptomics and Lipidomics of Epicardial Ectopic Fat

Overview

Cohort studies have shown that patients with obesity associated with metabolic abnormalities (metabolically unhealthy obesity) have an accumulation of ectopic fat deposits (EDF) linked to subcutaneous adipose tissue dysfunction. Although it is accepted that the storage capacity of subcutaneous adipose tissue is genetically determined, the genetic factors predisposing to adipose tissue distribution abnormalities remain poorly understood. The Angiosafe T2D cohort consists of 7200 highly phenotyped type 2 diabetes (T2D) patients. In 297 patients from this cohort (ancillary study), investigators assessed epicardial fat volume (EFV) using an artificial intelligence algorithm. In 42 of these patients, designated as early T2DM/DGE, an accumulation of epicardial fat and diabetes occurring before the age of 40 were observed, clinically approaching the clinical presentation of genetic lipodystrophy, although subcutaneous adipose tissue persisted in their case. This study will focus on a case-control study nested within the pre-existing cohort of T2D patients (Angiosafe T2D), and more specifically within this cohort on a subgroup of 42 patients with early-onset diabetes and an abnormal distribution of adipose tissue caracterized by ectopic fat accumulation. In order to understand the severe metabolic phenotype observed in this group of 42 patients, investigators propose to perform a multiomic analysis combining clinico-biological, exomic, transcriptomic and lipidomic data. This study will compare the rate of patients with at least one rare (\<1% general population) potentially pathogenic genetic variant in a coding region of the genetic lipodystrophy genes by whole exome sequencing in 42 early-onset T2DM and a high epicardial fat volume patients versus 42 patients without early-onset T2DM and/or high epicardial fat volume (control group).

Interventions

• Procedure Subcutaneous adipose tissue biopsy
  Under local anesthesia, subcutaneous adipose tissue will be collected from 2 puncture points in the umbilical region for a total volume of 2 mL.
• Other Blood sampling
  One 4 mL tube of blood will be collected

Primary outcome measures

• Frequency of variants genes [Time frame: Day 1]

Secondary outcome measures (3)

• Plasma and adipocyte lipidic profil determined by mass spectrometry [Time frame: Day 1]
• Integrative multiomic analysis including clinical, biological, exomic, transcriptomic and lipidomic data. [Time frame: Day 1]
• Gene expression profil in subcutaneous adipose tissue determined by mRNA sequencing [Time frame: Day 1]

Eligibility criteria

Inclusion Criteria for T2D/DGE patient:

• Adult patient of legal age included in the Angiosafe T2D multicenter study, having consented to the use of the data collected for research purposes.
• Patient who has signed the GENTLE informed consent form.
• Patient not objecting to re-use of data and samples collected in the Angiosafe T2D study
• Patient with type 2 diabetes according to ADA recommendations
• Age at diagnosis of diabetes less than or equal to 40 years and epicardial fat volume greater than 72 mL\*.
• Patient beneficiary or affiliated to a social security scheme

Inclusion Criteria for control patient:

• Adult patient of legal age included in the Angiosafe T2D multicenter study, having consented to the use of the data collected for research purposes.
• Patient who has signed the GENTLE informed consent form.
• Patient not objecting to re-use of data and samples collected in the Angiosafe T2D study
• Patient with type 2 diabetes according to ADA recommendations
• Age at diagnosis of diabetes greater than 40 and/or epicardial fat volume less than 72 mL
• Patient beneficiary or affiliated to a social security scheme

Exclusion criteria

• Type 1 diabetic patient
• Patient with monogenic diabetes
• Patient with diabetes secondary to pancreatic disease
• Pregnant or breast-feeding women, patients under guardianship, deprived of liberty.

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

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Other

Study locations

France · 1 center

• Assistance Publique - Hôpitaux de Marseille — Marseille

Identifiers

NCT: NCT06590415 · RCAPHM24_0060

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗