Effects of Various Bariatric Surgical Procedures on Intestinal TRL Metabolism in Obese Type 2 Diabetic Patients (MISTRAL)

Effects of Various Bariatric Surgical Procedures on Intestinal Triglyceride-rich-lipoprotein (TRL) Metabolism in Obese Type 2 Diabetic Patients

Rational: The world and french epidemic of obesity and diabetes represents a major problem of public health. The prevalence in France, in the adult population, is 15 % corresponding to 6.9 million people for obesity and 6 % corresponding to 3.9 million people for diabetes. Morbidly obesity (body mass index 40 kg/m²), the most serious, is more and more frequent. Cardiovascular diseases are the first cause of morbidity and mortality. The atherogenic dyslipidemia of these insulin-resistant obese type 2 diabetic patients characterized by the quartet: elevated plasma triglycerides, low high-density lipoprotein-cholesterol, increased proportion of small and dense low-density lipoproteins, is widely explained by the blood accumulation of TRL from the liver and the intestine, and represents a major cardiovascular risk factor. The overproduction of intestinal TRL (which apoprotein B48 is the specific tracer) is a constituent recently recognized of insulin-resistance and the atherogenous role of these intestinal TRL has been shown. In view of this important overmortality and the failures of the medical, nutritional, dietary and psychotherapeutic combined treatment, the bariatric surgery quickly developed. Two main procedures are performed: 1 based exclusively on the gastric restriction (the sleeve gastrectomy) and one associating a malabsorption (the gastric bypass).

Objectives: The main objective of this study is to compare the effect of each surgical procedure and the differential effect of the 2 bariatric surgery procedures on the production and clearance rates of the intestinal TRL. The secondary objectives are to compare the effect of each surgical procedure and the differential effect of the 2 bariatric surgery procedures on the production and clearance rates of the hepatic TRL and to document the potential links between the expected reduction of these productions after the surgery and the loss of weight, the improvement of the insulin-sensitivity, the changes in hormones, the decrease of the inflammatory state, the changes in energy expenditure, body composition and energy intake.

Methods: It is a multicentric, prospective, comparative study of cohorts. After identification of the eligible subjects, the kinetics (production and clearance rates) of intestinal and hepatic TRL will be performed in the hospital, using established stable isotope enrichment methodology (5,5,5-D3-L-Leucine), in 2 groups of obese patients (15 patients per surgery procedure), before and 6 months after the surgery.

Perspectives: A better understanding of the dyslipidemia of obese type 2 diabetic patients and the factors modulating this dyslipidemia may lead to develop new dietary and/or drugs and/or surgical treatments targeted at the enterocyte to improve the lipid profile of these patients and reduce the incidence of cardiovascular diseases. Moreover, a differential effect between the 2 surgical procedures could help to choose the best surgical procedure for obese type 2 diabetic patients depending on the lipid profile at baseline.

Study Overview

• Status: Unknown
• Conditions: Obesity; Diabetes
• Intervention / Treatment: Other: stable isotope enrichment methodology (5,5,5-D3-L-Leucine)

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13005
    • Recruiting
    • Assistance Publique Hôpitaux Marseille
    • Contact: Sophie Beliard, MD; Email: sophie.beliard@ap-hm.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject with a body mass index between 35 and 60 kg / m²
• Subject with no contradiction to the 2 surgical techniques studied: Sleeve Gastrectomy and Gastric Bypass
• Subject with type 2 diabetes as defined
• Subject not having presented cardiovascular events (myocardial infarct, stroke, peripheral ischemia) in the previous 6 months

Exclusion Criteria:

• Pregnant women

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sleeve gastrectomy; bariatric surgery procedure based exclusively on the gastric restriction (the sleeve gastrectomy).	Other: stable isotope enrichment methodology (5,5,5-D3-L-Leucine)
Experimental: gastric bypass; bariatric surgery procedure associating a malabsorption (the gastric bypass).	Other: stable isotope enrichment methodology (5,5,5-D3-L-Leucine)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
production and clearance rates of intestinal and hepatic TRL, in 2 groups of obese patients (15 patients per surgery procedure), before and 6 months after the surgery.	7 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Study Director: Urielle Desalbres, Assistance Publique Hôpitaux Marseille

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Anticipated): January 1, 2018
• Study Completion (Anticipated): January 1, 2019

Study Registration Dates

• First Submitted: January 5, 2015
• First Submitted That Met QC Criteria: January 5, 2015
• First Posted (Estimate): January 6, 2015

Study Record Updates

• Last Update Posted (Estimate): November 17, 2015
• Last Update Submitted That Met QC Criteria: November 16, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Other Study ID Numbers: 2014-15; RCAPHM14_0179 (Registry Identifier: APHM)