Changes in Insulin Sensitivity After Weight Loss

Changes in Insulin Sensitivity After Weight Loss Induced by Diet or Bariatric Surgery

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. The main hypothesis of this study is that weight loss induced by gastric bypass will induce a greater improvement in insulin sensitivity compared with gastric banding or low calorie diet. Subjects will be studied before and after weight loss. Studies consist of intravenous glucose tolerance test, body composition analysis, meal test, and energy expenditure.

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.