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Acetylsalicylic acid improves fat induced insulin resistance in vivo in man
Introduction: Insulin resistance is a key feature of the metabolic syndrome responsible for a great percentage of morbidity and mortality in industrialized nations. In animal studies fat induced insulin resistance could be diminished by therapy with salicylates. Therefore, we investigated the impact of pretreatment with acetylsalicylic acid on fat induced insulin resistance in man.
Methods: 10 healthy men (age 41.5±4.7yrs, BMI 25.1±3.8kg/m2) were included. Diabetes, IFG or IGT were exclusion criteria. Hyperinsulinemic euglycemic clamp test was performed with and without lipid infusion (Abbolipid 20% plus 0.4 IU heparin/kg body weight) started 2 hours before the clamp and with and without pretreatment with acetylsalicylic acid (4g/ 24h), respectively. For each person the degree of lipid induced insulin resistance is calculated as the decrease in glucose infusion rate during steady state condition induced by lipid infusion relative to the control clamp without lipid infusion or acetylsalicylic acid pretreatment. Student’s T-Test for paired analysis was used to test for significant differences.
Results: Lipid infusion markedly increased non-esterified fatty acids and diminished glucose infusion rate relative to control to 65.5% (±23.5%, p=0.001). Pretreatment with acetylsalicylic acid diminished glucose infusion rate to 76.8% (±27.1%, p=0.024). The decreases in glucose infusion rates between lipid infusion and lipid infusion plus pretreatment with acetylsalicylic acid were significantly different from each other (p=0.006). Acetylsalicylic acid pretreatmet by its own did not affect insulin resistance (p=0.75) and did not influence the increase in non-esterified fatty acid concentration.
Discussion: As seen in animal models acetylsalicylic acid pretreatment improved fat induced insulin resistance in healthy man. The precise molecular mechanism is so far unknown but our data support the hypothesis of fatty acids activating NFκB dependent pathways in man.