Proteomics in Morbid Obesity After Bariatric Surgery
Condition: Insulin Resistance; Proteomics; Morbid Obesity
MeSH terms: Obesity; Insulin Resistance; Obesity, Morbid
Study type: Observational

Summary: 
      Glycemic control is rapidly restored in patients with insulin resistance after bariatric
      surgery, in particular after the mal-absorptive one (i.e. Bilio-pancreatic diversion, BPD).
      To evaluate the mechanisms allowing restoration of insulin sensitivity after BPD the
      investigators aimed at identifying by using a proteomic approach plasma proteins or peptides
      that may be involved in the remarkably fast and explicit restoration of insulin sensitivity.
      In addition to the unbiased proteomics approach, a selection of recognized markers for
      metabolic control will be measured. These efforts all aim at an increased understanding of
      how insulin sensitivity is regulated and may provide novel ideas of how to treat insulin
      resistance and type 2-diabetes.
    

Detailed description: 
      Study design The study is designed as a single-centre, observational study. The patients will
      undergo routine analyses usually performed before and after biliopancreatic diversion surgery
      (BPD), independently of the participation to this specific protocol with the only exception
      of meal test. Twenty morbidly obese male subjects scheduled for BPD for will be included in
      the study.

      The inclusion and exclusion criteria are set as to create a sufficiently homogenous study
      population.

      As outlined in the study flow chart subjects will be studied and blood samples collected at 3
      weeks (+/- 1 week) and 4 days (+/- 1 day) before the day of BPD surgery (baseline-1 and
      baseline-2), at the day of surgery (day 0), every second day after surgery during the first
      week (immediate post surgery) as well as two and four weeks after surgery (post surgery-1 and
      post surgery-2). A deviation of +/- 2 days is allowed for the post surgery-1 and post
      surgery-2 visits.

      All fasting samples are obtained in the morning after an overnight fast (12 h). Immediate
      post surgery (fasting) samples will be collected after 12 h rest from parenteral nutrition
      from the arm not used for nutritional substitution during the first 4 days after surgery
      (when parenteral nutrition is given). The immediate post surgery (fasting) samples obtained
      from day 5 and forward after surgery, when subjects have started to eat, will be obtained in
      the morning after an overnight fast (12 h). Nutrient stimulation samples will be obtained at
      baseline-1 and 2 and post surgery-1 and 2 after intake of a test meal. A complete list of all
      procedures for each visit is provided in Table 1 and an overview of all planned blood
      samples, including volumes and purpose is provided in Table 2. Motivations for the collection
      of various samples are provided under section 10.3.1 "Proteomics analysis, experimental
      design issues".

      In case of discontinuation, additional subjects should be enrolled such that a complete set
      of samples from no less than 20 subjects can be obtained.

      Target subject population Inclusion criteria

        -  Morbidly obese male with a BMI >40 kg/m2 who, for their obesity disease, are eligible
           for bariatric surgery and have accepted to undergo BPD

        -  Confirmed insulin resistance; fasting serum insulin level > 60 pmol/L

        -  Age 25-55 years

        -  Weight stable for at least 6 months before the study (+/- 5 kg within the previous 6
           months)

        -  Stable medication

        -  Provision of informed consent, statistical analysis, and publications of obtained
           results Exclusion criteria

        -  Patients not eligible for BPD

        -  Incapacity to give a valid informed consent or unwilling to give the consent

        -  Patients eligible for BPD, but with:

             -  Type 2-diabetes mellitus

             -  Significant illness within the two weeks preceding surgery, as judged by the
                physician.

             -  Obvious infection (bacteria, virus etc)

             -  Major cardiovascular disease

             -  Major gastrointestinal, respiratory, or any hormonal disorders

             -  Medication affecting lipid metabolism within 3 months of the study

             -  History of drug addiction and/or alcohol use

             -  Suspected or confirmed poor compliance

             -  Exercise +/-3 times a week

             -  Blood donation within 12 weeks preceding screening visit
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Twenty male, morbidly obese subjects
      
Biospecimen description: 
      Serum and plasma samples at fasting and after a meal
    
Keywords: Bilio-pancreatic diversion; morbid obesity; insulin resistance; proteomics