Fat Cell Size in Insulin Resistance
Condition: Obesity
MeSH terms: Insulin Resistance
Study type: Observational

Summary: 
      This study, conducted at Stanford University in Palo Alto, California, will examine how
      insulin metabolism and cardiovascular risk are altered in response to weight loss. Insulin is
      a natural hormone that causes cells to remove glucose (sugar) from the blood. People who are
      insulin-sensitive remove glucose efficiently. People who are insulin-resistant require more
      insulin to remove glucose from the blood.

      Adult volunteers will be recruited for this study through advertisements in local newspapers
      in communities around Stanford University.

      Participants will undergo the following tests and procedures:

        -  Insulin sensitivity testing: Before beginning the study, participants will be tested for
           insulin sensitivity. For the test, two small catheters (plastic tubes) are placed into
           two veins - one for infusing glucose, insulin, and sandostatin (a drug that blocks
           insulin secretion from the pancreas), and one for drawing blood samples. The infusions
           are done over 3 hours. Blood samples are collected before, during, and at the end of the
           study to measure how well the cells remove glucose from the blood in response to
           insulin.

        -  Research diet: Participants are assigned to a low-calorie diet tailored to the
           individual's metabolic rate. The diets contain either 40 or 60 percent of total calories
           as carbohydrates, 40 or 20 percent as fat, and the rest as protein. People with type 2
           diabetes who are taking diabetes medicine with have a diet of 45 to 50 percent
           carbohydrates, 35 to 40 percent fat, and the rest protein.

        -  Meal profile: Before beginning the diet and after 4 months on the diet, participants are
           tested for the effects of the various study diets on control of blood sugar and fats. On
           the day of each test, participants have a physical examination and provide a medical
           history. Then, a small catheter is placed in a vein. Blood samples are drawn before
           breakfast and then hourly for up to 8 hours.

        -  Participants who are diabetic are randomly assigned to take one of three diabetes
           medications - rosiglitazone, glucophage, or a sulfonylurea compound - to help control
           blood glucose levels.

        -  Magnetic resonance imaging: This diagnostic test uses a strong magnetic field and radio
           waves to show structural and chemical changes in tissues. During the scan, the
           participant lies on a table in a narrow cylinder containing a magnetic field, wearing
           ear plugs to muffle loud knocking and thumping sounds that occur during the scanning
           process. He or she can speak with a staff member via an intercom system at all times
           during the procedure.

      In addition to these procedures, patients may be asked to have a fat cell biopsy. This is
      done to determine whether insulin-resistant people have fewer fat cells but more fat per cell
      than insulin-sensitive people. For this test, a small piece of fat tissue is surgically
      removed, under local anesthetic, from an area of the lower abdomen. With the participant's
      consent, genetic testing may be done on the fat tissue sample to look for genes that may link
      central obesity to insulin resistance.

      Some participants may be asked to be followed for an additional 3 months after completion of
      the study for a continued weight loss program. The follow-up includes weekly visits for
      weight measurements and a review of food records.
    

Detailed description: 
      Little is known about the turnover of adipose cells in the fat depots of normal animals and
      human subjects. However, microarray analysis of adipose cell gene expression in high risk
      insulin-resistant human subjects suggests that a reduced rate of adipose cell turnover is
      associated with enhanced adipose cell size and systemic insulin resistance. New technology
      now permits a detailed analysis of adipose cell size including the detection of smaller cells
      which may be in the process of active differentiation. We propose to examine the relationship
      between adipose cell size distribution and systemic insulin resistance in obese human
      subjects. Adipose tissue biopsies will be obtained at Stanford University under protocols and
      consent forms approved by the Stanford University IRB. Only procedures already being
      performed on subjects under these protocols will be used.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The NIH is involved with several Stanford protocols that have recruited both males &
        females between ages of 40-65 years of age who are either overweight patients but generally
        healthy, those with diabetes and cardiovascular medical conditions and/or are healthy
        volunteers.
      
Keywords: Multisizer 3; Signaling; Obesity; Type 2 Diabetes; Adipose Cell Turn Over