Fat Cell Size in Insulin Resistance

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.