The impact of sex on risk of cardiovascular disease and all-cause mortality in adults with or without diabetes mellitus: A comparison between the U.S. and Japan

Aims: To test a hypothesis that women with diabetes mellitus (DM)versus those without DM had a significantly higher risk of heart disease (HD), stroke and all-cause mortality than their male counterparts in the U.S. as well as in Japan. Methods: We analyzed two nationally representative datasets, one from the U.S. NHANES III cohort (n = 13,169), and the other from the Japan NIPPON DATA90 cohort (n = 7445). Hazard ratios (HRs)of DM for risk of mortality and sex-DM interaction effect on mortality were analyzed prospectively using Cox's proportional hazards regression models. Results: Patients with DM had significantly higher mortality from HD, stroke and all-cause mortality in the U.S. and in Japan. However, the HRs of DM versus non-DM for HD and all-cause mortality were significantly higher in women compared to men in the U.S. (sex-DM interaction: HR = 1.59, p = 0.01, and 1.24, p = 0.045 for HD and all-cause mortality), but the sex-DM interaction effect was not statistically significant in the Japanese cohort. Discussion: Patients with DM had a significantly higher risk of mortality than those without DM in the U.S. and Japan. However, women with DM versus those without DM had a higher relative risk of HD and all-cause mortality than their counterparts in men in the U.S, but this sex difference by DM status was not observed in the Japanese cohort. Whether the sex-difference effect of DM on HD and all-cause mortality is due to a difference in metabolic disorders between the two populations warrants consideration and further studies.