Changes in Insulin Sensitivity After Weight Loss

Patients who are scheduled for gastric bypass (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, peptide YY
(PYY), glucagon-like peptide 1 (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.

Inclusion criteria:

- Non-diabetic obese (BMI > 30) adult men and women between the ages of 18 and 75
scheduled to undergo

- gastric bypass (GBP)

- gastric banding (BND)

- Type 2 diabetes (HbA1c 6-12%) adult men and women between the ages of 18 and 75
scheduled to undergo gastric bypass.

- Type 2 diabetes (HbA1c 6-12%) adult men and women between the ages of 18 and 65 for
weight reduction with a very low caloric diet (VLCD).

- Type 2 diabetes mellitus scheduled to undergo sleeve gastrectomy (SG).

Exclusion criteria:

- Pregnancy.

- Age > 75 for surgery groups; Age > 65 for VLCD group.

- Treatment with glucocorticoids, anti-depressants, anti-psychotics, neuroleptics,
weight loss medications, experimental medication.

- Greater than a 5% change in total body weight in the 90 days prior to the study.

- History of untreated gallstones; hepatic or renal insufficiency, abnormal thyroid
stimulating hormone (TSH).

- Use of thiazolidinedione therapy.

- HbA1c > 12%.

- Use of dipeptidyl peptidase IV (DPP-IV) inhibitor or glucagon-like peptide 1 receptor
(GLP-1R) agonist for greater than 12 months within 3 months of the study.

- Fasting triglycerides > 400.

- Significant cardiovascular, neurologic, renal, gastrointestinal, or hematologic
disease.

- Inability to comply with or understand the study protocol as ascertained by the PI.

- We will not exclude individuals with body weight > 145 kg, but we do recognize that
such individuals are above the table weight limitations of the dual-energy x-ray
absorptiometry (DEXA) scan and body composition data will be unavailable for those
individuals.