The Effects of Anti-Inflammatory Treatment on Insulin Resistance in Healthy Volunteers

In healthy subjects, low-grade inflammation, as measured by serum levels of cytokines or acute phase proteins, is positively associated with adiposity. Recent studies indicate that chronic low-grade inflammation in non-diabetic individuals may cause decline in insulin sensitivity and increases the risk of developing type 2 diabetes. It has been proposed that reduction of low-grade inflammation may reduce the risk of development of type 2 diabetes. In agreement with this hypothesis, the class of anti-inflammatory drugs called salicylates (such as aspirin) that influence a specific anti-inflammatory pathway have been found to decrease plasma glucose levels and increase insulin sensitivity in rodents as well as people with type 2 diabetes. In the present study, we propose testing whether administration of the anti-inflammatory drug Salsalate improves insulin sensitivity in obese non-diabetic individuals and whether this improvement is related with a decrease in serum markers of inflammation. Subjects will be randomly assigned to two treatment groups: placebo or Salsalate (3g/d). An oral glucose tolerance test and a combined euglycemic/hyperglycemic clamp to assess insulin sensitivity and insulin secretion will be performed before and after seven days of treatment. Results of this study may help to identify novel strategies to prevent type 2 diabetes in high-risk groups.