Adipose Tissue Pre and Post Bariatric Surgery (ETAPP)

Evaluation of Adipose Tissue Pre and Post Bariatric Surgery

Published data suggest that inflammation and fibrosis of adipose tissue could be factors favoring the development of insulin resistance in obese individuals and that a decrease in the activity of the AMP-activity kinase protein (AMPK) could lead to these dysfunctions. However, very few data are available in humans.

There is also growing interest in persistent organic pollutants (POPs) as a cardiometabolic and type 2 diabetes (T2D) risk factor. There is some evidence to suggest that POPs directly contribute to lipid metabolism dysfunction and insulin resistance. Additionally, POPs are stocked in adipose tissue. The accumulation of POPs in adipose tissue therefore limits their bioavailability to other organs, thus reducing their systemic toxicity. It has been observed that a large amplitude weight loss leads to a significant increase in POPs in the blood.

The goal of this project is to identify adipose tissue factors/dysfunctions that contribute to insulin resistance and type 2 diabetes associated with obesity in humans and thus raise avenues for screening and treatment of these metabolic complications. More specifically, the objectives are:

• To study the relationship between AMPK, fibrosis and inflammation of adipose tissue and their role in the development of insulin resistance and T2D associated with obesity;
• To examine the relationship between POPs and the cardiometabolic profile.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity
• Intervention / Treatment: Procedure: Bariatric surgery; Other: Blood sampling; Other: Blood pressure; Other: Anthropometric measurements; Other: Body composition; Other: Resting metabolic rate; Other: Food intake; Procedure: Adipose tissue biopsy

• Study Type: Observational
• Enrollment (Actual): 98

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2W 1R7
      • Institut de recherches cliniques de Montreal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The study population will be composed of obese individuals with type 2 diabetes, insulin-sensitive obese individuals and insulin-resistant obese individuals, all awaiting bariatric surgery.

Description

Inclusion Criteria:

1. Awaiting bariatric surgery
2. BMI ≥ 35 kg/m2 without cardiometabolic complications or ≥ 30 kg/m2 if presence of type 2 diabetes or hypertension
3. ≥ 18 years old
4. Non smoker
5. Sedentary (less than 3 hours of regular physical activity per week)

Exclusion Criteria:

1. Type 1 diabetes
2. Acute event in the last 3 months (myocardial infarction, cerebrovascular hemorrhage or transient cerebral ischemia, unstable angina, peripheral vascular disease, revascularization or angioplasty, recent hospitalization for more than 4 days)
3. Infection in the last month (fever, antibiotics treatment)
4. Cancer in the last 3 years
5. Chronic inflammatory disease
6. Pharmacologic treatment (any medication affecting glucose metabolism (except those for diabetes), hypotensive medication unless stable dose for at least 1 month, lipid-lowering medication unless stable dose for at least 1 month)
7. Uncontrolled disease of pituitary or thyroid gland
8. Bleeding disorders
9. Alcohol or drug abuses
10. Claustrophobia

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Obese with type 2 diabetes	Procedure: Bariatric surgery; Sleeve gastrectomy; Other: Blood sampling; Blood samples will be collected to measure glucose, insulin, albumin, uric acid, HbA1c, lipids, hepatic enzymes, TSH, hs-CRP, complete blood cell counts and persistant organic pollutants; Other: Blood pressure; Systolic and diastolic blood pressure will be measured.; Other: Anthropometric measurements; Body weight, height and waist circumference will be measured.; Other: Body composition; Body composition will be evaluated by dual-energy X-ray absorptiometry.; Other: Resting metabolic rate; Resting metabolic rate will be measured by indirect calorimetry.; Other: Food intake; Food intake, energy intake and food quality will be evaluated using the food frequence questionnaire.; Procedure: Adipose tissue biopsy; A sample of 3-5g of adipose tissue will be collected under local anesthesia by needle aspiration in the periumbilical region.
Obese insulin-sensitive	Procedure: Bariatric surgery; Sleeve gastrectomy; Other: Blood sampling; Blood samples will be collected to measure glucose, insulin, albumin, uric acid, HbA1c, lipids, hepatic enzymes, TSH, hs-CRP, complete blood cell counts and persistant organic pollutants; Other: Blood pressure; Systolic and diastolic blood pressure will be measured.; Other: Anthropometric measurements; Body weight, height and waist circumference will be measured.; Other: Body composition; Body composition will be evaluated by dual-energy X-ray absorptiometry.; Other: Resting metabolic rate; Resting metabolic rate will be measured by indirect calorimetry.; Other: Food intake; Food intake, energy intake and food quality will be evaluated using the food frequence questionnaire.; Procedure: Adipose tissue biopsy; A sample of 3-5g of adipose tissue will be collected under local anesthesia by needle aspiration in the periumbilical region.
Obese insulin-resistant	Procedure: Bariatric surgery; Sleeve gastrectomy; Other: Blood sampling; Blood samples will be collected to measure glucose, insulin, albumin, uric acid, HbA1c, lipids, hepatic enzymes, TSH, hs-CRP, complete blood cell counts and persistant organic pollutants; Other: Blood pressure; Systolic and diastolic blood pressure will be measured.; Other: Anthropometric measurements; Body weight, height and waist circumference will be measured.; Other: Body composition; Body composition will be evaluated by dual-energy X-ray absorptiometry.; Other: Resting metabolic rate; Resting metabolic rate will be measured by indirect calorimetry.; Other: Food intake; Food intake, energy intake and food quality will be evaluated using the food frequence questionnaire.; Procedure: Adipose tissue biopsy; A sample of 3-5g of adipose tissue will be collected under local anesthesia by needle aspiration in the periumbilical region.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adipose tissue fibrosis using qRT-PCR, immunoblotting, histochemistry and immunohistochemistry	Before bariatric surgery
Adipose tissue fibrosis using qRT-PCR, immunoblotting, histochemistry and immunohistochemistry	6 months after bariatric surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
Calory intake	Before bariatric surgery
Calory intake	3 months after bariatric surgery
Calory intake	6 months after bariatric surgery
Food quality using the Food Frequency Questionnaire	Before bariatric surgery
Food quality using the Food Frequency Questionnaire	3 months after bariatric surgery
Food quality using the Food Frequency Questionnaire	6 months after bariatric surgery
Persistant organic pollutants measured by high-resolution chromatography combined with high-resolution mass spectrometry	Before bariatric surgery
Persistant organic pollutants measured by high-resolution chromatography combined with high-resolution mass spectrometry	3 months after bariatric surgery
Persistant organic pollutants measured by high-resolution chromatography combined with high-resolution mass spectrometry	6 months after bariatric surgery
AMP-activated protein kinase	Before bariatric surgery
AMP-activated protein kinase	3 months after bariatric surgery
AMP-activated protein kinase	6 months after bariatric surgery
Inflammation in adipose tissue using qRT-PCR, immunoblotting and immunohistochemistry	Before bariatric surgery
Inflammation in adipose tissue using qRT-PCR, immunoblotting and immunohistochemistry	3 months after bariatric surgery
Inflammation in adipose tissue using qRT-PCR, immunoblotting and immunohistochemistry	6 months after bariatric surgery

Collaborators and Investigators

• Sponsor: Institut de Recherches Cliniques de Montreal

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 25, 2012
• Primary Completion (ANTICIPATED): July 31, 2022
• Study Completion (ANTICIPATED): September 30, 2022

Study Registration Dates

• First Submitted: March 14, 2022
• First Submitted That Met QC Criteria: March 22, 2022
• First Posted (ACTUAL): March 31, 2022

Study Record Updates

• Last Update Posted (ACTUAL): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Type 2 diabetes; Bariatric surgery; Persistant organic pollutants
• Other Study ID Numbers: 2011-22 (Other Identifier: AP HM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No