Bariatric surgery procedures promote weight loss by limiting the amount of food consumed through reduction of the size of the stomach and by decreasing absorption of nutrients through reorganizing or bypassing portions of the small intestine. Among the procedures used to induce weight loss, sleeve gastrectomy (SG) was initially developed in the early 90's as the restrictive component of a biliopancreatic diversion with duodenal switch (BPD-DS). It was then offered by laparoscopy as a staged-approach in order to reduce peri-operative complications in high-risk patients. The second step of the surgery (i.e. the duodenal switch) was planned when sufficient weight loss had been obtained. However, it was observed that some patients experienced appreciable weight loss with the SG alone, and did not require a second-stage surgery, thus avoiding the side-effects of a malabsorptive surgery. This led to the surge in popularity of SG as a stand-alone operation, because of its relative technical simplicity, feasibility, and good outcomes. Multiple mechanisms have been postulated to induce metabolic recovery and weight loss following surgery. The independent effects of each component of the BPD-DS with SG have never been investigated in humans within a well-controlled study design. The general objective of the present project is to assess the impact of each component of the BPD-DS and SG, either combined of separated, on physiological variables potentially responsible for metabolic recovery. Patients will be randomized to undergo one of three surgical sequences: 1) SG followed by BPD-DS one year later; 2) BPD-DS followed by SG one year later; or 3) SG and BPD-DS within a single operation. A series of tests will be performed at baseline, at 1 year, and 2 years after the initial surgery. We propose two Specific Aims to asses 1) the impact of each surgical component on the hormonal determinants of metabolic recovery; and 2) the impact of weight loss responses on subcutaneous and visceral adipose tissue function improvements. This project will help better understand the mechanisms underlying metabolic recovery following weight loss surgery.

Inclusion Criteria:

• Men and Women between 18-60 years old;
• BMI ≥ 45 à ≤ 55 kg/m2;
• Subjects capable of understanding and being able to sign a consent form;
• Subjects capable of following the protocol directives, including the proposed visits (timeline);
• Subjects living within a reasonable distance from the hospital and capable of being present at all required visits.

Exclusion Criteria:

• Pregnant women or women who plan on becoming pregnant during the study, or women in fertile age range who refuse proper contraceptive methods during the study. (Must have negative pregnancy test at the moment of enrollment and use medically acceptable contraception which include: oral contraceptives, injectable or implantable contraceptives, intrauterine devices or double-barrier method ie. condoms and diaphragm);
• Diabetics
• Subjects with HbA1c ≥ 6,5 % or fasting Glucose ≥7mmol/l or non-fasting Glucose ≥11mmol/l;
• Previous oesophagal, gastric or bariatric surgery;
• Irritable bowel syndrome, unexplained intermittent vomiting, severe abdominal pain, diarrhea or chronic constipation;
• History of duodenal or gastric ulcers;
• Pre-operative hypoalbuminuria (<35g/l);
• History of renal disease, hepatic disease (cirrhosis) or severe cardiac or pulmonary disease;
• Corticosteroid intake in the previous month;
• Presence of psychiatric problems or behavioral issues that could limit subject's capacity at understanding the procedure and to conform to medical/surgical recommendations;
• History of drug use or alcoholism in previous 12 months before study;
• History of inflammatory diseases of the gastro-intestinal tract (Esophagitis, varices, gastric or duodenal ulcers, Crohn's disease, congenital or acquired anomalies of the digestive tract).