This study, conducted at the Phoenix Indian Medical Center, Phoenix, Arizona, will determine whether reducing subclinical inflammation lessens insulin resistance in healthy, obese volunteers. The study findings may lead to new strategies for preventing type 2 diabetes. In diabetes, blood sugar is higher than normal and can result in serious medical problems, such as blindness and kidney failure. People with subclinical inflammation-inflammation that does not produce symptoms, such as fever, pain, or skin redness-are at increased risk for diabetes. Although the reasons for this are not completely understood, it is known that subclinical inflammation exacerbates insulin resistance, which is a cause of diabetes. Insulin is a hormone that helps control blood sugar, and when it does not work properly, the condition is known as insulin resistance.

Normal, healthy volunteers between 18 and 45 years old with a body mass index of at least 30 kg/m2 and who have subclinical inflammation (determined by blood tests) may be eligible for this study. Candidates must be non-smokers and must not have an alcohol or drug problem. Candidates will be screened with a medical history and physical examination, electrocardiogram, and blood and urine tests. Participants will maintain a standard diet and undergo the following tests and procedures during a 14-day inpatient stay at the Phoenix Indian Medical Center:

• Day 1: Screening tests, as described above.
• Day 4: Dual energy x-ray absorptiometry (DXA) to determine percentage of body that is fat tissue. For this test, the subject lies on a table for 15 to 60 minutes for scanning with low-dose x-rays.
• Days 4 and 11: Oral glucose tolerance tests to measure blood glucose and insulin levels. For this test, the subject drinks a glucose (sugar) solution. Blood samples are drawn through an IV catheter before the test begins and at 0.5, 1, 2, and 3 hours after drinking the solution.
• Days 1, 4, and 11: Blood test to assess inflammation. At admission and during the first of two oral glucose tolerance tests, blood will be evaluated for an inflammatory score calculated from blood markers of inflammation.
• Days 5 and 12: Glucose clamp test to measure (1) the effect of insulin infused into a vein on the body's ability to take up sugar from the blood and (2) the effect of sugar infused into a vein on the body's ability to produce insulin. For this test, a catheter (thin, plastic tube) is put in an arm vein and in a vein of the hand on the other side of the body. While insulin is infused through one catheter, blood sugar is checked every 5 minutes. A sugar solution is infused as necessary to keep the blood sugar level steady or to increase sugar to a set of predetermined levels. A radioactive sugar is also infused during the test (at a very slow rate for 4 hours) to determine how much sugar the body produces by itself.
• Days 6 through 12: An anti-inflammatory drug or placebo to test the effect of an anti-inflammatory on insulin resistance. Volunteers will be randomly assigned to take Rofecoxib or Salsalate-drugs approved by the Food and Drug Administration to treat inflammation, pain, and fever-or a placebo (look-alike pill with no active ingredient) for 7 days.
• Blood test on day 14 to assess liver enzyme levels.

Participants will be discharged from the hospital on day 14 of the study.