Changes in Insulin Sensitivity After Weight Loss

• Insulin Sensitivity [ Time Frame: 2-8 weeks ] [ Designated as safety issue: No ]
  

• Body Composition [ Time Frame: 2-8 weeks ] [ Designated as safety issue: No ]
  
• Resting Energy Expenditure [ Time Frame: Up to 4 hrs post-meal ] [ Designated as safety issue: No ]
  Subjects will be in a post-absorptive state for 12 hours and after IV insertion and blood draw they will rest for 30 min followed by measurement of REE for 30 mins. They will then consume a liquid meal over a 15min period, followed by a 30 min rest and repeat REE measurements for 30 min per hr for 4 hrs.
  
  

Obesity and weight gain both contribute independently to the development of type 2 diabetes. Obesity is associated with a pre-diabetic disease state, often called insulin resistance. Studies have found that some diabetic patients who undergo gastric bypass (GBP) are cured of their diabetes within 12 weeks after surgery, prior to any significant amount of weight loss. Since the flow of nutrients from the stomach to the small intestine is interrupted after GBP, the anatomic modification may cause a greater improvement in insulin sensitivity than with other forms of weight loss. Changes in levels of hormones released from the gastrointestinal tract in response to food intake may underlie this increased insulin sensitivity.

This study is designed to compare the changes in insulin sensitivity as well as gastrointestinal hormone levels in diabetic and non-diabetic obese individuals who are undergoing weight loss procedures. Patients who are scheduled for GBP, sleeve gastrectomy (SG), or simple caloric restriction with gastric banding (BND) or a very low calorie diet (VLCD) will be examined at baseline weight, and when 6-10% total body weight has been lost. We will measure insulin sensitivity with an intravenous glucose tolerance test, and fasting levels of hormones that regulate food intake and insulin sensitivity, such as ghrelin, PYY, GLP1 and leptin. Fat mass and skeletal muscle mass will be measured by dual photon absorptiometry (DXA). We will also measure the hormonal and thermic response to food with a liquid test meal and energy expenditure by indirect calorimetry. This measures how many calories are burned at rest and the in response to food. Subjects with diabetes will continue to be studied with the same protocol on an annual basis out to 5 years in order to determine the rate of remission of diabetes and the durability of this effect as subjects tend to regain some body weight over time.

Subjects with diabetes will also be followed every three months for the first year after the initial weight loss for HbA1c and fasting glucose levels. The results of this study may lead to new understanding about changes in insulin sensitivity, body composition and hormonal profile, as well as changes in energy expenditure with weight loss after bariatric surgery or with simple caloric restriction. With this greater understanding, new treatments for obesity and diabetes, that do not require surgery, may be developed.