Protection Against Insulin Resistance in Obesity

SCREENING PROCEDURES Participants will undergo a battery of initial screening tests including: a detailed health history and physical examination, a physical activity questionnaire, and a body composition assessment. All women will undergo a urine pregnancy test.

GENERAL STUDY DESIGN To avoid potential confounding hormonal effects, all women will be studied in the early follicular phase of their menstrual cycle. Subjects will be advised of what they should be eating in the 3 days leading up to their hospital visit to maintain their weight. Subjects will also complete a three day food journal before their hospital visit. The day prior to the study trial admission, subjects will need to eat pre-prepared standardized meals for breakfast, lunch, dinner and an evening snack that the study team has given them.

Subjects will be admitted to the Michigan Clinical Research Unit (MCRU) in the morning after a 12-hour, overnight fast. After arrival, subjects will rest quietly in their room for about 30 minutes. The study team will then measure subjects resting metabolic rate for about 20 minutes. After this test, an intravenous (IV) catheter will be placed for infusions and a second IV will be placed in vein of the opposite arm for blood sampling.

After the IV placement, the study team will begin a tracer-labeled glucose, or "sugar," infusion. The study team will then remove a small sample of muscle from the subjects thigh. This muscle biopsy procedure involves numbing a nickel-sized portion of the skin of the thigh with a local anesthetic, making a small incision (1/4 inch), and removing a small piece of muscle (approximately the size of 2-3 grains of rice). The incision will then be closed with a piece of sterile tape. The study team will also obtain a small sample of fat tissue from the area just underneath the skin near the belly button. This procedure involves numbing a small region of skin near the belly button with a local anesthetic, using a needle a small amount of fat tissue is removed from underneath the skin. During the procedure subjects will feel some pinching and pulling, but it should not be very painful. The injury resulting from the muscle and fat tissue biopsies is rather minor. Subjects will likely have some bruising and mild soreness, but it should not prevent them from performing their general daily activities.

Approximately 2.5 hours after admission, the study team will begin the tracer-labeled fat infusion. The tracer-labeled fats the study team are infusing occur naturally in the body. By injecting a slightly greater amount of this substance than what is already in the body the study team will be able to measure the rate of fat breakdown and fat burning. After about 50 minutes of the infusion, three blood samples will be obtained in 5 min intervals.