Postprandial Metabolism After Bariatric Surgery in Type 2 Diabetes
Condition: Type 2 Diabetes; Obese
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional

Summary: 
      Bariatric surgery procedures have now been firmly demonstrated to lead to significant
      improvement and even, in many cases, complete reversal of abnormal glucose homeostasis in
      type 2 diabetes (T2D). Various surgery procedures are can be performed to induce weight loss.
      The most striking anti-diabetic effects are observed with biliopancreatic diversion with
      duodenal switch (BPD-DS), followed by Roux-in-Y gastric bypass (RYGB) and sleeve gastrectomy
      (SG). The first two procedures induce both a restriction of energy intake and a low
      absorption of dietary fatty acids while the latter exclusively targets energy intake
      restriction. The investigator and others have shown that improvement of T2D occurs within
      days after BPD-DS or RYGB in the vast majority of patients, prior to any significant weight
      loss. This very rapid metabolic recovery is explained by a normalization of β-cell function
      after meal challenges and ameliorated hepatic insulin sensitivity. The investigator and
      others have shown that these acute anti-diabetic effects are mostly recapitulated by matched
      caloric restriction, independent of changes in gastrointestinal hormones, showing the
      importance of gastrointestinal-derived energy fluxes for acute diabetes control. Muscle
      insulin sensitivity, on the other hand, improves more slowly in association with weight loss,
      demonstrating the heterogeneous metabolic response of the various organs to BPD-DS. Some
      preliminary studies also demonstrate a rapid reduction of NEFA levels and production rate
      upon i.v. administration of lipids during euglycemic hyperinsulinemic clamps. This very rapid
      improvement in NEFA tolerance strongly suggests that adipose tissue storage of circulating
      fatty acids also improves very rapidly, prior to any significant weight loss, after BPD-DS.
      It may also suggest an acceleration of oxidative fatty acid metabolism in organs such as the
      liver, the heart and/or skeletal muscles. Studies of the rapid metabolic changes after
      bariatric surgery conducted thus far rapidly improved the understanding of the fundamental
      pathogenic defects of T2D. However, much remains to be understood about the acute changes in
      gastrointestinal-derived metabolic fluxes, organ-specific metabolic responses to bariatric
      surgery and their relationship with the reversal of T2D. Using in vivo methodological
      approaches, the investigator proposes to investigate the early organ-specific changes in
      dietary fatty acid metabolism in response to BPD-DS vs. SG and their relation to improved
      systemic changes in glucose homeostasis, insulin sensitivity and β-cell function in patients
      with T2D.
    

Detailed description: 
      Participants will undergo a metabolic study before and 8 to 12 days after bariatric surgery
      after a 12-hour fast and a three-day food and physical activity diary with accelerometry. The
      patients recover very rapidly from the surgery and will be able to participate to the
      proposed investigations the week after their hospitalization on an outpatient basis on the
      earliest week day between 8 and 12 days after the surgery procedure. The metabolic study is a
      6-hour meal test using Positron Emitting Tomography (PET).
    

Intervention name(s): biliopancreatic diversion with duodenal switch; sleeve gastrectomy; liquid meal; PET/scan; [7,7,8,8-2H]-palmitate; indirect calorimetry
Intervention type(s): Procedure; Procedure; Other; Radiation; Other; Device
Intervention description(s): will be consumed over 30 minutes with [U-13C]-palmitate (0.2 g mixed in the liquid meal) and H2-glucose; a dynamic and whole body PET acquisition will be performed on a thoraco-abdominal segment, 150 minutes after an oral administration of 18FTHA; i.v. administration of [7,7,8,8-2H]-palmitate (in 25% human albumin) from time -60 to 360 min.; will be performed every hour throughout the protocol along with exhaled breath collection
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment