A Longitudinal Study on Short-term Effects of Gastric Bypass on Glucose Homeostasis in Obesity
Condition: Morbid Obesity
MeSH terms: Obesity; Obesity, Morbid
Study type: Observational

Summary: 
      The purpose of this study is to quantify the relative contribution of improved insulin
      sensitivity and improved insulin secretion to the glycaemic effect of bariatric surgery.
    

Detailed description: 
      In 1987 Pories et al. (1) published that after gastric bypass 99% of morbidly obese patients
      became and remained euglycaemic over time. However, the most interesting observation of these
      authors (1) was that the patients were converted to euglycaemia within 10 days of the
      operation, even if before they required large doses of insulin. Thereafter, we ourselves
      (2-6) as well as other Authors (7,8) have found that both mainly malabsorptive bariatric and
      mainly restrictive surgery are effective in producing early improvement/resolution of type 2
      diabetes, also in normal weight (9) or overweight-obese subjects (10).

      Until now the mechanisms through which bariatric surgery operate in improving insulin
      sensitivity and, consequently, diabetes control have not been elucidated. To complicate the
      picture there is the fact that after bariatric surgery patients are not allowed to eat for a
      time that is longer as the entity of the abdominal trauma increases. In fact, after
      laparoscopic bariatric surgery the patients are re-alimented in the 3rd post-operative day
      while after open surgery the time length before re-alimentation is about 7 days. Although in
      most centres the patients receive a parenteral nutrition covering the energy needs while they
      remain at rest, in some other centres they are only re-hydrated. Thus, it might be
      hypothesised that fasting can contribute to the improvement of glucose disposal. The data in
      the literature counteract this possibility as many Authors (11-15) have demonstrated that a
      very-low calorie diet (VLCD) is essentially unable to improve insulin sensitivity at least in
      the short run, when the weight loss is minimal. In this regard, Jazet et al. (11) found that
      the glucose control amelioration in diabetic subjects undergoing a 2-day VLCD was a reduction
      in the hepatic glucose production rather than an improvement in the whole-body glucose
      disposal. Similarly, Christiansen et al (12) observed the increase in the glucose metabolic
      clearance rate (MCR) was not apparent before day 20 of energy restriction, when the weight
      loss became significant. In another study, diabetic patients under a 4-day energy-restricted
      diet (providing 4620 ± 1050 kJ/d) had a deterioration of both basal glucose MCR and
      insulin-stimulated glucose disposal (13).

      Recently, Laferrère et al (16) compared the late (1 month) effect of an equivalent weight
      loss by RYGB or by diet in two groups of matched morbidly obese patients with type 2 diabetes
      mellitus. The glucose area under-the-curve (AUC) after an oral glucose tolerance test (OGTT)
      and glucose levels at 120' were significantly lower after RYGB compared with diet (P = 0.014
      and P = 0.001, respectively).

      Another important aspect of the weight loss is the modulation of lipolysis. Many studies have
      shown that obese subjects are insulin resistant at the level of adipose tissue, ie, despite
      high plasma insulin levels lipolysis and FFA release are not suppressed. It is therefore
      interesting to study the changes in lipolysis before and after surgery and also the ability
      of insulin (e.g., during the euglycemic, hyperinsulinemic clamp) to suppress peripheral
      lipolysis. By infusing deuterated glycerol we will be able to estimate glycerol rate of
      appearance, which is the best available index of lipolysis. In fact intracellular
      triglyceride (TG) hydrolysis results in the release of one mole of glycerol and 3 moles of
      FFA. While the FFA can be re-esterified intracellularly, and thus do not appear into the
      systemic circulation, glycerol cannot be re-esterified since the adipocyte lacks glycerol
      kinase. Thus, all glycerol derived from intracellular TG hydrolysis is released into the
      circulation and can be traced by deuterated glycerol. We have used this technique previously
      in diabetic subjects (17), in subjects with NASH as well as in obese subjects under VLCD
      (18). In the latter study we have shown that VLCD improved adipose tissue IR.

      As far as we know, no data are available in the literature comparing the effect of RYGB with
      a purely restrictive bariatric procedure in order to take into account simultaneously the
      effect of the surgical trauma and that of the reduced food intake in the early post-operative
      period.

      The main goal of this study is to determine the immediate effect of Roux-en-Y gastric bypass
      surgery on glucose homeostasis, factoring out the confounding effects of the surgical
      approach (incl. laparoscopy) and of the post-operative fasting.

      To this purpose, patients of the two bariatric surgery groups (Roux-en-Y gastric bypass and
      gastric banding) are matched as far as feasible. Primary parameter is insulin resistance (as
      assessed by Matsuda index). Further the same BMI inclusion criteria apply for both groups
      (BMI > 30 kg/m2 and < 55 kg/m2). While age, gender and BMI within the specified range are
      also expected to influence the read-outs, no matching for these baseline characteristics is
      foreseen due to feasibility issues.

      Patients receive oral food typically from day 3 or 4 after laparoscopic bariatric surgery.
      This post-operative food intake is restricted to 800 - 1000 kcal/day, usually divided in 6
      small meals, with the following composition 55% carbohydrates, 30% lipids and 15% proteins;
      saturated lipids ~ 10% . A similar caloric intake restriction will be imposed during the
      1-week diet period prior to Visit 3, which will be done 10 +/- 2 weeks before the operation
      in order to allow the patients a complete recovery of his/her body weight which must be kept
      constant before the next study in order to avoid methodological biases.
    

Intervention name(s): Study on insulin sensitivity after diet or bariatric surgery; gastric bypass
Intervention type(s): Other; Other
Intervention description(s): Group A: 1 week of low calorie diet before gastric banding a new study 1 week after gastric banding Group B: 1 week of low calorie diet before gastric bypass a new study 1 week after gastric bypass; Group B: 1 week of low calorie diet before gastric bypass a new study 1 week after gastric bypass
Intervention MeSH terms: Insulin
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Twenty morbidly obese subjects scheduled for RYGB or LAGB for will be included in the
        study.
      
Biospecimen description: 
      Blood sampling
    
Keywords: Morbid obesity; Insulin resistance; Euglycemic clamp