Type 2 Diabetes
Conditions
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).
Interventions
PROCEDURESubcutaneous 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.
OTHERBlood sampling
One 4 mL tube of blood will be collected
Sponsors
Assistance Publique Hopitaux De Marseille
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
France
Contacts
Primary ContactBenedicte Gaborit, Pr
Backup ContactLauren Agnelli
Outcome results
None listed