Trancriptomics and Lipidomics of Epicardial Ectopic Fat
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Frequency of variants genes
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
T2D/DGE patients
Diagnostic age of diabètes mellitus less than or equal to 40 years and epicardial fat volume greater than 72 mL.
干预措施: Subcutaneous adipose tissue biopsy (Procedure)
T2D/DGE patients
Diagnostic age of diabètes mellitus less than or equal to 40 years and epicardial fat volume greater than 72 mL.
干预措施: Blood sampling (Other)
Control patients
Age at diagnosis of diabetes greater than 40 and/or epicardial fat volume less than 72 mL.
干预措施: Subcutaneous adipose tissue biopsy (Procedure)
Control patients
Age at diagnosis of diabetes greater than 40 and/or epicardial fat volume less than 72 mL.
干预措施: Blood sampling (Other)
结局指标
主要结局
Frequency of variants genes
时间窗: 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%.
次要结局
- 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)