Person:

Cook, Nancy

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. RESEARCH DESIGN AND 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 ≥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.

Objective: To evaluate the association of kidney function with cardiovascular disease and mortality among apparently healthy women. Design: Prospective cohort study. Setting: Women’s Health Study, United States. Participants: 27 939 female health professionals aged ≥45 who were free of cardiovascular disease and other major disease and who provided a blood sample at study entry. Main outcome measures: Time to cardiovascular disease (non-fatal stroke, non-fatal myocardial infarction, coronary revascularisation procedures, or death from cardiovascular cause), specific cardiovascular disease events, and all-cause mortality. End points were confirmed after review of medical records and death certificates. Results: Glomerular filtration rate (GFR) was estimated with the abbreviated Modification of Diet in Renal Disease Study equation. At baseline, 1315 (4.7%) women had GFR <60 ml/min/1.73 m2. During 12 years of follow-up, 1199 incident cardiovascular disease events and 856 deaths (179 from cardiovascular disease) occurred. Compared with women with GFR ≥90 ml/min/1.73 m2, the multivariable adjusted hazard ratios for any first cardiovascular disease were 0.95 (95% CI 0.83 to 1.08), 0.84 (0.70 to 1.00), and 1.00 (0.79 to 1.27) among women with GFR of 75-89.9, 60-74.9, and <60 ml/min/1.73 m2, respectively; the equivalent hazard ratios for all cause mortality were 0.93 (0.79 to 1.09), 1.03 (0.85 to 1.26), and 1.09 (0.83 to 1.45). Similar null findings were observed for myocardial infarction, stroke, coronary revascularisation, and non-cardiovascular death. However, an increased risk of death from cardiovascular disease was found among women with GFR <60 ml/min/1.73 m2 (hazard ratio 1.68 (1.02 to 2.79)). Conclusions: In this large cohort of women, a glomerular filtration rate <60 ml/min/1.73 m2 was associated with increased risk of cardiovascular disease death but not other cardiovascular disease events or non-cardiovascular disease mortality. We observed no increase in risk of any of the outcomes among women with less severe impairment of kidney function.

OBJECTIVE: Homocysteinemia may play an etiologic role in the pathogenesis of type 2 diabetes by promoting oxidative stress, systemic inflammation, and endothelial dysfunction. We investigated whether homocysteine-lowering treatment by B vitamin supplementation prevents the risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: The Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a randomized, double-blind, placebo-controlled trial of 5,442 female health professionals aged ≥40 years with a history of cardiovascular disease (CVD) or three or more CVD risk factors, included 4,252 women free of diabetes at baseline. Participants were randomly assigned to either an active treatment group (daily intake of a combination pill of 2.5 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12) or to the placebo group. RESULTS: During a median follow-up of 7.3 years, 504 women had an incident diagnosis of type 2 diabetes. Overall, there was no significant difference between the active treatment group and the placebo group in diabetes risk (relative risk 0.94 [95% CI 0.79–1.11]; P = 0.46), despite significant lowering of homocysteine levels. Also, there was no evidence for effect modifications by baseline intakes of dietary folate, vitamin B6, and vitamin B12. In a sensitivity analysis, the null result remained for women compliant with their study pills (0.92 [0.76–1.10]; P = 0.36). CONCLUSIONS: Lowering homocysteine levels by daily supplementation with folic acid and vitamins B6 and B12 did not reduce the risk of developing type 2 diabetes among women at high risk for CVD.