Acetylsalicylic acid improves lipid-induced insulin resistance in healthy men.
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.


METHODS
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.


METHODS
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.
Möhlig
Matthias
M
German Institute of Human Nutrition Potsdam- Rehbruecke, Department of Clinical Nutrition, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany. mmoehlig@mail.dife.de
Freudenberg
Madlen
M
Bobbert
Thomas
T
Ristow
Michael
M
Rochlitz
Helmut
H
Weickert
Martin O
MO
Pfeiffer
Andreas F H
AF
Spranger
Joachim
J
D052242:Adiponectin / Q000097:blood; D001241:Aspirin / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D012016:Reference Values
D052242:Adiponectin; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D015850:Interleukin-6; D002097:C-Reactive Protein; D001241:Aspirin