Effects of Bariatric Surgery on Insulin
Condition: Obesity; Bariatric Surgery; Gastric Bypass; Weight Loss; Hyperglycemia
MeSH terms: Hyperglycemia; Weight Loss
Study type: Observational

Summary: 
      This study, conducted at the NIH Clinical Research Unit (CRU) at the Phoenix Indian Medical
      Center, will compare the effects of two methods of bariatric surgery, the adjustable BAND and
      Roux-en-Y gastric bypass, on insulin. Bariatric surgery is a treatment for achieving and
      maintaining weight loss. The study will look at how this surgery might improve how insulin (a
      hormone important for regulating blood sugar levels) is made and works in the body and the
      possible role of changes in other hormones produced by the gut (stomach and intestines).

      People between 18 and 50 years of age who are scheduled to have either laparoscopic
      adjustable BAND or Roux-en-Y gastric bypass surgery may be eligible for this study.
      Candidates are screened about 4 to 6 weeks before their surgery with a medical history, blood
      tests and an oral glucose tolerance test for diabetes.

      Participants spend 4 days at the CRU or 2 days overnight and an out-patient visit
      approximately 4 to 6 weeks before their surgery and again 3 to 6 weeks after their surgery.
      They return for a 4-6 hour visit at the CRU at 6 months, 1 and 2 years after surgery and for
      half-day outpatient visits at 3, 4 and 5 years after surgery for the following procedures:

        -  Blood and urine tests, including a pregnancy test for women. (4-day and 2-day admissions
           and years, 3, 4 and 5)

        -  DEXA, an x-ray scan to determine body fat content. (4-day and 2-day admissions and
           years, 3, 4 and 5)

        -  MRI scan to measure fat tissue in the abdomen. (4-day and 2-day admissions and years, 3,
           4 and 5)

        -  Intravenous (I.V.) glucose tolerance test for risk of obesity and diabetes. A sugar
           solution is given through a needle in a vein of one arm and blood samples are drawn
           through another needle in a vein in the other arm. (4-day admissions)

        -  Meal test to measure blood sugar and insulin and gut hormone levels after a meal. After
           an I.V. line is placed in an arm vein, the subject eats breakfast over 20 minutes. Blood
           samples are collected halfway through the meal, at the end of the meal, and at 15, 30,
           60, 90, 120 and 180 minutes after completing the meal. Subjects fill out questionnaires
           on feelings of hunger and fullness before, during and after the meal test. (4-day and
           2-day admissions)

        -  Glucose clamp test to measure the effect on the body of insulin given through a vein. An
           I.V line is placed in a vein in the arm and in a vein of the hand on the other side of
           the body. While insulin is infused through one I.V., blood sugar levels are checked
           every 5 minutes and a sugar solution is given into a vein as needed. A radioactive sugar
           is also infused very slowly over 4 hours to determine how much sugar the body produces
           by itself. (4-day admissions)
    

Detailed description: 
      Bariatric surgery is a treatment for obesity that, in many cases, also improves fasting blood
      sugar levels even in patients with type 2 diabetes (T2DM) - within days or weeks after
      surgery . Both inability to use insulin (insulin resistance) and inability to make enough
      insulin when needed (impaired insulin secretion) must be present for T2DM to occur, and both
      have been reported to improve after bariatric surgery. It is generally thought that the
      immediate improvement in blood sugar levels, including remission of T2DM or "prediabetes" in
      many patients, following bariatric surgery is due to the markedly reduced intake of calories.
      However, it is not known why blood sugar levels before and after meals tend to improve
      earlier and to a greater extent in patients who have a Roux en-Y gastric bypass (RYGB)
      procedure than in patients who have either the adjustable gastric banding (BAND) or sleeve
      gastrectomy (SG) procedure. It has been proposed that the surgical alteration of the gut and
      subsequent re-routing of food that occurs with RYGB procedure results in unique changes in
      how the gut and pancreas (the organ that secretes insulin) respond to food and that these
      changes are also related to improved insulin resistance and/or secretion.

      The purpose of this protocol is to study, before and after surgery, volunteers who either
      have normal or impaired ("pre-diabetic") blood sugar regulation and who have been approved to
      undergo either elective RYGBP, BAND or SG bariatric surgery (n=16 each per surgery group,
      total = 48 individuals with normal blood sugars; n= 10 each per surgery group, total = 30
      individuals with prediabetes). The primary aims are to compare the early effects of the BAND,
      SG and RYGBP procedures on: a) the ability to maintain blood sugar levels, b) how much
      insulin is made (secretion) and works (insulin action) in the body, and c) responses of gut
      and pancreas hormones to a meal test before any significant weight loss occurs after surgery.
      To achieve these goals, we initially will screen volunteers at the NIH Clinical Research Unit
      in Phoenix approximately 4-6 weeks prior to surgery (1-day outpatient visit) to determine
      oral glucose tolerance status (OGTT). Within 3 weeks (1-4 weeks prior to surgery), subjects
      will then be admitted (4-day in-patient stay) or a 2 day overnight stay and an outpatient
      (4-6 hour) visit to measure weight, body fatness (DXA scan), waist circumference, insulin
      resistance, insulin secretion, fasting blood sugar and hemoglobin A1c (HbA1c; a substance
      that indicates how well the body keeps overall blood sugar levels in a normal range), and
      plasma hormone responses of the gut and pancreas to a standard meal test. These measurements
      will be repeated at 3-6 weeks following surgery.

      Secondary aims are to: 1) compare long-term effects (up to 5 years) of BAND, SG or RYGBP
      surgery on fasting blood sugar and HbA1c levels, 2) determine if these levels are related to
      the responses of gut and pancreas hormones during a meal test, and 3) determine whether
      pre-op or early post-op measures of insulin secretion, insulin action, or responses of gut
      and pancreas hormones to a meal can predict long-term levels of fasting blood sugar and HbA1c
      after accounting for changes in weight or body fat. To achieve these goals, subjects will
      return to the NIH CRU (out-patient, 4-6 hour visit) at 6, 12, and 24 months after surgery to
      have repeat measurements of body weight, fatness (DXA, non-contrast MRI of waist and thigh),
      waist circumference, fasting blood sugar and HbA1c levels and the gut and pancreatic hormone
      responses to a meal test. Thereafter, subjects will have annual outpatient measurements of
      body weight, body fat and fasting blood sugar and HbA1c levels at 3, 4 and 5 years after
      surgery.
    

Time perspective: Prospective
Keywords: Bariatric Surgery; Insulin Action; Insulin Secretion; Insulin Resistance; Gut Hormones; Obesity