Effects of Bariatric Surgery on Insulin
Effects of Bariatric Surgery on Insulin
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)
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.
-  INCLUSION CRITERIA:

 -  Subjects must initially qualify for bariatric surgery according to current NIH
 guidelines, which require the presence of either morbid obesity alone (BMI greater
 than 40 kg/m(2)) or a BMI greater than 35 kg/m(2) along with at least 2 other
 co-morbidities.

 -  Patients with conditions such as sleep apnea, mild steatohepatitis, GERD, asthma (not
 requiring oral steroids) and osteoarthritis can be considered for participation.

 -  Subject with undiagnosed diabetes (2-h glucose greater than 200 mg/dl during initial
 screening OGTT) will be included in the IGR group ONLY IF BOTH fasting plasma glucose
 is less than 126 mg/dl and HbA1c is less than 7 percent, suggesting early T2DM.

 -  Subjects must be at least 18 years of age and less than 150 kg body weight.

 -  Males and females of all ethnic minorities will be included.

 EXCLUSION CRITERIA:

 Because of the indications for bariatric surgery, many potential subjects will have
 underlying co-morbidities associated with obesity. For this protocol, subjects will be
 excluded for the following:

 -  Current smoking

 -  Previously diagnosed diabetes

 -  Other endocrine disorders, such as Cushing's disease, pituitary disorders, and thyroid
 disease

 -  Significant hepatic or renal disease (ALT and AST greater than 3-fold above upper
 limit of normal range, cirrhosis, active hepatitis B or C, serum creatinine greater
 than 1.5 mg/dl or presence of protein in urine dipstick)

 -  Active tuberculosis (self-report)

 -  Major pulmonary disorders including physician diagnosed chronic obstructive pulmonary
 diseases other than obstructive sleep apnea

 -  Cardiovascular diseases, including coronary heart disease, heart failure, arrhythmias,
 and peripheral artery disease

 -  Hypertension (according to the World Health Organization diagnostic criteria), treated
 or uncontrolled

 -  Gastrointestinal disease, including inflammatory bowel diseases (e.g. Crohn's disease
 and ulcerative colitis), malabsorption syndromes (e.g. celiac disease), gastric ulcer
 (active)

 -  Central nervous system disease, including previous history of cerebrovascular
 accidents, dementia, and neurodegenerative disorders

 -  Cancer requiring treatment in the past five years, except for non-melanoma skin
 cancers or cancers that have clearly been cured or in the opinion of the investigator
 carry an excellent prognosis

 -  Psychiatric conditions or behavior or current alcohol or illicit drug use that would
 be incompatible with safe and successful participation in this study

 -  Recent use (within 30 days) of anorexiant medications, antibiotics, contraceptives or
 fertility drugs or recent use (within 5 days) of anti inflammatory agents

 -  Pregnancy or breastfeeding (to avoid radiation exposure to fetus or nursing infant)