Obesity is associated with impaired platelet-inhibitory effect of acetylsalicylic acid in nondiabetic subjects.
OBJECTIVE
Platelet aggregation responses to acetylsalicylic acid (ASA) show considerable interindividual variation, the causes of which are largely unknown. We determined whether variation in insulin action is associated with that of ASA on platelets.


METHODS
In all, 10 nonobese (age 50+/-3 y, BMI 25+/-1 kg/m(2)) and 11 obese (age 52+/-2 y, BMI 32+/-1 kg/m(2)) subjects.


METHODS
Insulin sensitivity of glucose uptake was determined by the euglycemic insulin clamp technique. Platelet aggregation responses to four doses of arachidonic acid (AA) and adenosine diphosphate (ADP) were assessed in platelet-rich plasma before and 1 h after ingestion of 50 mg ASA using Born's turbidometric aggregometer.


RESULTS
Whole-body insulin sensitivity (M-value 0-180 min) was 36% lower in the obese (4.5+/-0.6) than the nonobese (7.1+/-0.6 mg/kg min, P<0.01) group. Before ASA, all doses of AA induced complete aggregation. After ASA ingestion, ASA inhibited maximal aggregation more in the nonobese than the obese group at AA concentrations of 0.75, 1 and 1.5 mmol/l (P=0.016 for ANOVA). ADP-induced aggregation at high doses (2 and 3 micromol/l) was also less inhibited in the obese group. In vivo insulin sensitivity (r=-0.68, P<0.001 for 1 mmol/l AA) and BMI (r=0.58, P<0.01 for 1 mmol/l AA) were closely correlated with residual aggregation after ASA administration.


CONCLUSIONS
These data demonstrate that obese insulin-resistant subjects have a blunted response to platelet-inhibitory effect of ASA. If this blunted effect is of a single dose of ASA preserved in continuous use, it could contribute to the increased risk of atherothrombosis in insulin-resistant individuals.
Tamminen
M
M
Division of Diabetes, University of Helsinki, Finland.
Lassila
R
R
Westerbacka
J
J
Vehkavaara
S
S
Yki-Järvinen
H
H
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000704:Analysis of Variance; D016718:Arachidonic Acid / Q000494:pharmacology; D001161:Arteriosclerosis / Q000209:etiology; D001241:Aspirin / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D012307:Risk Factors
D001786:Blood Glucose; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D001241:Aspirin