A randomized trial of low-dose aspirin in the prevention of clinical type 2 diabetes in women.
OBJECTIVE
Subclinical inflammation is linked with the development of type 2 diabetes, and epidemiologic data suggest that this association may be stronger in women. Although small clinical studies have shown a prominent hypoglycemic effect of short-term high-dose aspirin, no randomized trials have directly evaluated the efficacy of aspirin in diabetes prevention at doses acceptable for use in routine clinical practice. We evaluated whether chronic low-dose aspirin prevents the development of clinical diabetes among initially healthy American women.


METHODS
Subjects were enrolled in the Women's Health Study, a 10-year randomized double-blind, placebo-controlled trial of aspirin and vitamin E for primary prevention of cardiovascular disease and cancer. Between 1992 and 1995, 38,716 women aged > or =45 years and free of clinical diabetes were randomly assigned to either low-dose aspirin or placebo (median follow-up 10.2 years). Documented clinical type 2 diabetes was prospectively evaluated throughout the trial.


RESULTS
Among women randomly assigned to receive aspirin (n = 19,326) or placebo (n = 19,390), there was no statistically significant difference in the incidence of type 2 diabetes. There were 849 cases of diabetes in the aspirin group and 847 in the placebo group (rate ratio 1.01 [95% CI 0.91-1.11]). Stratification by diabetes risk factors including age, BMI, family history of diabetes, physical activity, A1C, and high-sensitivity C-reactive protein did not support a modulating effect of these variables. Analyses accounting for treatment duration and adherence similarly found no beneficial effects.


CONCLUSIONS
These data suggest that long-term low-dose aspirin does not prevent the development of clinical type 2 diabetes in initially healthy women.
Pradhan
Aruna D
AD
Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. apradhan@partners.org.
Cook
Nancy R
NR
Manson
Joann E
JE
Ridker
Paul M
PM
Buring
Julie E
JE
D000368:Aged; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000517:prevention & control*; D005006:Ethnicity; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D008875:Middle Aged; D010349:Patient Compliance; D010919:Placebos; D011322:Primary Prevention; D044469:Racial Groups; D018570:Risk Assessment; D014810:Vitamin E / Q000627:therapeutic use
D002316:Cardiotonic Agents; D007004:Hypoglycemic Agents; D010919:Placebos; D014810:Vitamin E; D001241:Aspirin