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NCT Number: NCT06590415

Trancriptomics and Lipidomics of Epicardial Ectopic Fat

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).

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Key information

Conditions

Type 2 Diabetes Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Assistance Publique - Hôpitaux de Marseille

Marseille, 13005, France

Location contact

Benedicte Gaborit

CONTACT

Lauren Agnelli

CONTACT

[email protected]

0491435186

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

Blood sampling

Other

One 4 mL tube of blood will be collected

Primary outcomes

  1. Frequency of variants genes

    Time frame: 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 outcomes

  1. Plasma and adipocyte lipidic profil determined by mass spectrometry

    Time frame: 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)

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

    Time frame: Day 1

    identification of a multiomic signature that would differentiate the 2 groups: Early T2D/DGE and controls.

  3. Gene expression profil in subcutaneous adipose tissue determined by mRNA sequencing

    Time frame: 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

Study contacts

Contact information is provided by the study sponsor or research team.

Benedicte Gaborit, Pr

CONTACT

[email protected]

0491968723

Lauren Agnelli

CONTACT

[email protected]

0491435186

Sponsors and collaborators

Lead sponsor

Assistance Publique Hopitaux De Marseille

Other

Registry information

Acronym: GENTLE

Important dates

Study start
2024
Primary completion
2026
Study completion
2027
First posted
Sep 19, 2024
Registry last updated
Sep 19, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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