The Effect of Salsalate on Insulin Action and Secretion

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This study is a randomized, placebo controlled trial to examine the effects of a short course of salsalate (3 grams per day for 7 days) on insulin action and secretion, using gold standard measurements of insulin action, the euglycemic-hyperinsulinemic clamp, and insulin secretion, the hyperglycemic clamp technique. During this study measures of inflammation are collected prior to and following the intervention to investigate how changes in these markers are associated with changes insulin action. Monocytes are also collected prior and following the intervention to measure NF-B activity to specifically investigate the role of the IKK beta pathway in insulin action. Recruitment was completed in February, 2008. After one week, volunteers who received Salsalate had lower fasting plasma glucose concentrations, lower glucose area under the curve during an oral glucose tolerance test, and lower c-reactive protein concentrations. Glucose infusion rates during the clamp were also higher in those who received Salsalate, but so were steady state insulin concentrations. After accounting for the change in insulin concentration, there was no difference in glucose uptake between the placebo and Salsalate group. Therefore, Salsalate improves glycemia, but via its effect on insulin clearance, not via a direct effect on insulin action. In support of this, Salsalate treatment did not decrease NF-B activity. Results of the effect of Salsalate on insulin secretion are currently pending.