Acetylsalicylic Acid Improves Lipid-Induced Insulin Resistance in Healthy Men

Context and Objective: Insulin resistance is a central feature of type 2 diabetes. Salicylates prevent lipid-induced insulin resistance in rodents by interrupting inflammatory pathways. We therefore investigated whether salicylates reduce lipid-induced insulin resistance in humans by affecting inflammatory pathways as reflected by serum adipocytokines. Participants and Intervention: Ten healthy men were included in a crossover intervention study. Four euglycemic-hyperinsulinemic clamps were performed, one without pretreatment, one with prior 2-h lipid infusion, one after pretreatment with 4 g acetylsalicylic acid (ASA), and one with ASA pretreatment and prior lipid infusion. Main Outcome Measure: Lipid-induced insulin resistance was quantified by the euglycemic-hyperinsulinemic clamp technique running at least 2 h. Repeated-measures ANOVA on two factors was used for comparison, and results were Bonferroni adjusted for multiple measurements. ASA effects on serum adipocytokines were addressed by comparing the areas under the curves. Results: Glucose infusion rate (M value) of the control clamp without pretreatment was 6.3 (± 0.6) mg/kg·min. ASA pretreatment did not change glucose infusion rates (P = 0.6). Lipid infusion significantly decreased the M value to 4.1 (± 0.6) mg/kg·min (P = 0.008). After ASA pretreatment and lipid infusion, the M value was 4.8 (± 0.7) mg/kg·min and was significantly improved, compared with the lipid-only clamp (P = 0.036 after Bonferroni’s adjustment). General biomarkers of inflammatory processes (IL-6, C-reactive protein), the insulin-sensitizing mediator adiponectin, and circulating adiponectin oligomers were unchanged by ASA pretreatment. Conclusions: ASA pretreatment attenuated lipid-induced insulin resistance in healthy humans. This acute insulin-sensitizing effect of ASA was unrelated to changes of circulating inflammatory markers.