Protection Against Insulin Resistance in Obesity
Condition: Obesity; Insulin Resistance
MeSH terms: Obesity; Insulin Resistance
Study type: Interventional

Summary: 
      The overall goal of this project is to identify factors that "protect" some obese adults from
      becoming insulin resistant. Identifying mechanisms that help protect some obese adults from
      developing insulin resistance could lead to novel, targeted therapeutic and/or preventative
      strategies for obese adults who are insulin resistant.
    

Detailed description: 
      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.

      After, the study team will begin a hyperinsulinemic-euglycemic clamp procedure (a procedure
      to measure the body's sensitivity to insulin). During this procedure the study team will
      infuse insulin and glucose through the IV and will collect blood samples every 5 minutes for
      the duration of the procedure to monitor the subjects blood glucose and blood insulin
      concentrations. This procedure is designed to last 2 hours. The study team will change the
      infusion rate of glucose accordingly to ensure that the subjects blood sugar is maintained at
      a healthy/normal level. The study team will also infuse a small amount of potassium to make
      sure potassium concentrations remain at healthy/normal levels. About 30 minutes after
      starting this procedure to measure the body's sensitivity to insulin, the study team will
      collect another sample of muscle from the thigh and fat tissue from the area just underneath
      the skin near the belly button. After completing the hyperinsulinemic-euglycemic clamp
      procedure, subjects will be provided a meal, and the study team will continue to monitor the
      subjects blood glucose concentration until stable.

      When the subjects vital signs are stable, the study team will also measure percent body fat
      using a Dual Energy X-ray Absorptiometry (DEXA) and intra-abdominal fat by Magnetic resonance
      imaging (MRI). When the DEXA scan and MRI tests have been completed, subjects will be
      discharged from the hospital. Depending on scheduling, however, the DEXA scan and MRI tests
      may be performed on a separate occasion from the study trial admission.
    

Intervention name(s): hyperinsulinemic-euglycemic clamp
Intervention type(s): Drug
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science