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Date of release: 11 May, 2009

Low-dose aspirin: does it prevent type 2 diabetes in women?


In a recently published study [1], the authors try to prove the possibility of using low-dose aspirin for the prevention of clinical type 2 diabetes in women. Information on long-term use of aspirin (100 mg every other day) to reduce the incidence of type 2 diabetes was gathered from the Women’s Health Study (WHS) as part of a study in primary prevention of cardiovascular disease and cancer over a 10-year period in healthy women, randomizing 38,716 patients. The median follow-up was 10.2 years among women randomly assigned to receive aspirin (n = 19,326) or placebo (n = 19,390), and 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 (relative risk (RR) 1.01; 95% confidence interval (CI) 0.91–1.11). Treatment duration ≤ 5 years (RR 0.99; 95% CI 0.86–1.15) or ≥ 5 years (RR 1.01; 95% CI 0.90–1.15) did not vary significantly across subgroups of women at high risk for diabetes. Some significant risk reductions in total cholesterol and low density lipoprotein cholesterol levels were noted but no correlation to lowering the risk of incidence in type 2 diabetes was observed. Higher rates of clinically significant bleeding episodes were seen in the aspirin arm compared to placebo (RR 1.22, p < 0.001).

Comment

The ability of salicylates to reduce glucose levels has been described long ago. There is evidence of the link between inflammation and the development of type 2 diabetes. Insulin resistance and type 2 diabetes are obesity-linked inflammatory disorders [2]. Aspirin’s hypoglycemic response might involve anti-inflammatory pathways distinct from effects on prostaglandin synthesis. Despite the high rate of side-effects, high doses (3–10 g/day for 3 days to 3 weeks) have positive effects on diabetic patients [3]. At the end of 2 weeks, aspirin at a dose of 7 g/day lowered fasting glucose (~25%) and C-reactive protein (~15%) while improving glucose tolerance (~20%), reducing basal hepatic glucose production (20%), and increasing insulin-stimulated peripheral glucose uptake (20%). Importantly, however, the high dose of aspirin used in all of these studies is known to cause serious side-effects [3].  
 
Lower doses have positive responses on metabolic markers. As mentioned above, information on long-term use of aspirin (100 mg every other day) to reduce the incidence of type 2 diabetes in women showed that risk was not changed [1]. However, previous studies demonstrated that low-dose aspirin prevented ischemic strokes (RR 0.83; 95% CI 0.69–0.99). In women aged > 65 years, the risk of myocardial infarction decreased as well (RR 0.66; 95% CI 0.44–0.97) [4]. It is noteworthy that a gender-based difference in the cardiovascular outcomes of low-dose aspirin therapy has been well established [5], and these data were the basis for the 2009 recommendations of the US Preventive Services Task Force on aspirin for the prevention of cardiovascular disease [6]. Basically, these recommendations encourage the use of aspirin to prevent ischemic stroke in women and myocardial infarction in men when potential benefit outweighs potential harm of bleeding.

Comentario

Konstantinos Tserotas
Department of Obstetrics & Gynecology, Complejo Hospitalario Metropolitano, Caja del Seguro Social de Panama

    References

  1. Pradhan AD, Cook NR, Manson JE, Ridker PM, Buring JE. A randomized trial of low-dose aspirin in the prevention of clinical type 2 diabetes in women. Diabetes Care 2009;32:3-8. Published January 2009.
    http://www.ncbi.nlm.nih.gov/pubmed/18835953

  2. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest 2006;116:1793-801.
    http://www.ncbi.nlm.nih.gov/pubmed/16823477

  3. Hundal RS, Petersen KF, Mayerson AB, et al. Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes. J Clin Invest 2002;109:1321-6.
    http://www.ncbi.nlm.nih.gov/pubmed/12021247

  4. Ridker PM, Cook NR, Lee IM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med 2005;352:1293-304.
    http://www.ncbi.nlm.nih.gov/pubmed/15753114

  5. Berger JS, Roncaglioni MC, Avanzini F, et al. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA 2006;295:306-13.
    http://www.ncbi.nlm.nih.gov/pubmed/16418466

  6. Aspirin for the Prevention of Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement. Ann Intern Med 2009;150:396-404. Published March 17, 2009.
    http://www.ncbi.nlm.nih.gov/pubmed/19293072