Trancriptomics and Lipidomics of Epicardial Ectopic Fat

NCT06590415 | Not Yet Recruiting

• 1 other identifier: RCAPHM24_0060
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

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).

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Frequency of variants genes

  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%.

  Day 1

Secondary Outcomes (3)

• Plasma and adipocyte lipidic profil determined by mass spectrometry

  Day 1

• Integrative multiomic analysis including clinical, biological, exomic, transcriptomic and lipidomic data.

  Day 1

• Gene expression profil in subcutaneous adipose tissue determined by mRNA sequencing

  Day 1

Study Arms (2)

T2D/DGE patients

EXPERIMENTAL

Diagnostic age of diabètes mellitus less than or equal to 40 years and epicardial fat volume greater than 72 mL.

Procedure: Subcutaneous adipose tissue biopsy; Other: Blood sampling

Control patients

ACTIVE COMPARATOR

Age at diagnosis of diabetes greater than 40 and/or epicardial fat volume less than 72 mL.

Procedure: Subcutaneous adipose tissue biopsy; Other: Blood sampling

Interventions

Subcutaneous adipose tissue biopsy PROCEDURE

Under local anesthesia, subcutaneous adipose tissue will be collected from 2 puncture points in the umbilical region for a total volume of 2 mL.

Control patients; T2D/DGE patients

Blood sampling OTHER

One 4 mL tube of blood will be collected

Control patients; T2D/DGE patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Assistance Publique - Hôpitaux de Marseille

Marseille, 13005, France

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Benedicte Gaborit, Pr

CONTACT

0491968723; benedicte.gaborit@ap-hm.fr

Lauren Agnelli

CONTACT

0491435186; lauren.agnelli@ap-hm.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2024
• First Posted: September 19, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

FR (1)