Trancriptomics and Lipidomics of Epicardial Ectopic Fat

Not Applicable

Not yet recruiting

• Conditions: Type 2 Diabetes
• Interventions: Procedure: Subcutaneous adipose tissue biopsy; Other: Blood sampling

• Registration Number: NCT06590415
• Lead Sponsor: Assistance Publique Hopitaux De Marseille

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-09
• Study First Submitted: 2024-09-03
• Study First Submitted QC: 2024-09-06
• Last Update Submitted: 2024-09-06
• Study First Posted: 2024-09-10
• Last Update Posted: 2024-09-10
• Study Start: 2024-10-01
• Primary Completion: 2026-10-01
• Study Completion: 2027-04-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 84

Inclusion Criteria

Not provided

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
T2D/DGE patients	Subcutaneous adipose tissue biopsy	Diagnostic age of diabètes mellitus less than or equal to 40 years and epicardial fat volume greater than 72 mL.
T2D/DGE patients	Blood sampling	Diagnostic age of diabètes mellitus less than or equal to 40 years and epicardial fat volume greater than 72 mL.
Control patients	Subcutaneous adipose tissue biopsy	Age at diagnosis of diabetes greater than 40 and/or epicardial fat volume less than 72 mL.
Control patients	Blood sampling	Age at diagnosis of diabetes greater than 40 and/or epicardial fat volume less than 72 mL.

Primary Outcome Measures

Name	Time	Method
Frequency of variants genes	Day 1	Higher frequency of rare heterozygous missense variants of lipodystrophy genes, or the presence of variants more often classified as pathogenic or of unknown significance (according to the ACMG classification) in the target group compared with the control group.; A variant is considered rare if its frequency in GnomAD is \< 1%.

Secondary Outcome Measures

Name	Time	Method
Plasma and adipocyte lipidic profil determined by mass spectrometry	Day 1	Identification of plasma and adipocyte lipid species whose expression is significantly altered in patients according to their phenotype and genotype (T2D/DGE versus controls)
Integrative multiomic analysis including clinical, biological, exomic, transcriptomic and lipidomic data.	Day 1	identification of a multiomic signature that would differentiate the 2 groups: Early T2D/DGE and controls.
Gene expression profil in subcutaneous adipose tissue determined by mRNA sequencing	Day 1	identification of genes whose expression is significantly altered in patients according to their phenotype and genotype (comparison of early T2D/DGE versus controls) in subcutaneous adipose tissue

Trial Locations

Locations (1)

Assistance Publique - Hôpitaux de Marseille; 🇫🇷 Marseille, France