Clinical trial NCT01129297: A Biological Atlas of Severe Obesity (Biological Tissue Collection)
Official title: Influence of the Glycemic and Ponderal Status on Tissues Gene Expression (Biological Tissue Collection)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Obesity
Glucose Intolerance
Diabetes
Keywords: Obesity
surgery
genetic expression
collection of samples
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
First posted: 2010-05-24
Enrollment: 20000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Recruiting: Clinical Medical Center from the north of France

Brief summary: Type 2 diabetes and obesity are both multifactorial diseases resulting from gene-environment interactions. However, this interaction, as well as the specific effect of each polymorphism, remains poorly understood.

We now proposed a prospective cohort study to improve our understanding of the influence of phenotypic characteristics on gene expression in tissues involved in glucose and/or lipid metabolism by collecting different biological samples.

Detailed description: Type 2 diabetes (T2D) is a disease commonly associated with obesity, which is an important risk factor for this condition. More than 80% of the diabetic subjects are obese. By analogy with the metabolic syndrome, the close association between obesity and T2D justifies the recognition of a new disease entity named by the neologism "diabesity".

This study will examine the contribution of different genetic variants on "diabesity" development, by integrating multiple genomics approaches (linkage analysis on whole genome, transcriptomics and bioinformatics) and analysis of biological pathways in relevant animals models and humans.

Eligibility criteria: Inclusion Criteria:

* Age between 18 and 65 years
* Indication of abdominal surgery requiring a laparotomy or laparoscopy for bariatric surgery, cholecystectomy, or parietal surgical
* Phenotype corresponding to one of the following four cases :

  1. Body Mass Index ≥ 35 kg/m2 and diabetes defined by a fasting blood glucose ≥ 7 mmol/l and/or ≥ to 11.1 mmol/l, 120 minutes after ingestion of glucose (hyperglycemia caused by oral route)
  2. Body Mass Index ≥ 35 kg/m2 with intolerance glucose defined by a fasting blood glucose\> 6 mmol/L and \<7 mmol/l and/or\> 7.8 mmol/l and \<11.1 mmol/l , 120 minutes after ingestion of glucose (hyperglycemia caused by oral route)
  3. Body Mass Index ≥ 35 kg/m2 without diabetes defined by a blood glucose ≤ 6 mmol/L and / or ≤ 7.8 mmol/l, 120 minutes after ingestion of glucose (hyperglycemia caused by oral route)
  4. Body Mass Index \<27 kg/m2 without diabetes defined by a blood glucose ≤ 6 mmol/L and / or ≤ 7.8 mmol/l, 120 minutes after ingestion of glucose (hyperglycemia caused by oral route)

5)27 \<Body Mass Index \<35 kg/m2 without diabetes defined by a blood glucose ≤ 6 mmol/L and / or ≤ 7.8 mmol/l, 120 minutes after ingestion of glucose (hyperglycemia caused by oral route)

Exclusion Criteria:

* unable to receive clear information
* refusal to sign the consent form
* pathology associated judged by the surgeon, may increase the risk of adverse events related to sampling tissue

Primary outcomes:
measure: Study the influence of phenotypic characteristics on gene expression of tissues involved in glucose metabolism
timeFrame: Baseline
Secondary outcomes:
measure: Correlation between gene expression and tissue insulin resistance index (HOMA2) (The Homeostasis Model Assessment)
timeFrame: 1 year
measure: Correlation between gene expression and tissue insulin resistance index (HOMA2) (The Homeostasis Model Assessment)
timeFrame: 2 years
measure: Correlation between gene expression and tissue insulin resistance index (HOMA2) (The Homeostasis Model Assessment)
timeFrame: 5 years
measure: Prospective assessment of clinical and biological features before and after bariatric surgery
timeFrame: 1 year
measure: Prospective assessment of clinical and biological features before and after bariatric surgery
timeFrame: 2 years
measure: Prospective assessment of clinical ans biological features before and after bariatric surgery
timeFrame: 5 years
measure: Genotype-Phenotype correlation
timeFrame: Baseline
Other outcomes:
Locations:
city: Lille
country: France
facility: Lille University Hospital
state: Nord
Study officials:
affiliation: Lille University Hospital
name: Francois PATTOU, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Margerie D, Lefebvre P, Raverdy V, Schwahn U, Ruetten H, Larsen P, Duhamel A, Labreuche J, Thuillier D, Derudas B, Gheeraert C, Dehondt H, Dhalluin Q, Alexandre J, Caiazzo R, Nesslany P, Verkindt H, Pattou F, Staels B. Hepatic transcriptomic signatures of statin treatment are associated with impaired glucose homeostasis in severely obese patients. BMC Med Genomics. 2019 Jun 3;12(1):80. doi: 10.1186/s12920-019-0536-1.
citation: Lien F, Berthier A, Bouchaert E, Gheeraert C, Alexandre J, Porez G, Prawitt J, Dehondt H, Ploton M, Colin S, Lucas A, Patrice A, Pattou F, Diemer H, Van Dorsselaer A, Rachez C, Kamilic J, Groen AK, Staels B, Lefebvre P. Metformin interferes with bile acid homeostasis through AMPK-FXR crosstalk. J Clin Invest. 2014 Mar;124(3):1037-51. doi: 10.1172/JCI68815. Epub 2014 Feb 17.