Effects of Bariatric Surgery on Insulin

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.