Sex-specific relevance of diabetes to occlusive vascular and other mortality : a collaborative meta-analysis of individual data from 980 793 adults from 68 prospective studies

Summary Background Several studies have shown that diabetes confers a higher relative riskof vascularmortality among women than among men, but whether this increased relative riskin women exists across age groups and within defined levels of other risk factors is uncertain. We aimed to determine whether differences in established risk factors, such as blood pressure, BMI, smoking, and cholesterol, explain the higher relative risksof vascularmortality among women than among men. Methods In our meta-analysis, we obtained individual participant-level data from studies included in the Prospective Studies Collaboration and the Asia Pacific Cohort Studies Collaboration that had obtained baseline information on age, sex, diabetes, total cholesterol, blood pressure, tobacco use, height, and weight. Data on causes of death were obtained from medical death certificates. We used Cox regression models to assess the relevance of diabetes (any type) to occlusive vascularmortality (ischaemic heart disease, ischaemic stroke, or other atherosclerotic deaths) by age, sex, and other major vascularrisk factors, and to assess whether the associations of blood pressure, total cholesterol, and body-mass index (BMI) to occlusive vascularmortality are modified by diabetes. Results Individual participant-level data were analysed from 980 793 adults. During 9·8 million person-years of follow-up, among participants aged between 35 and 89 years, 19 686 (25·6%) of 76 965 deaths were attributed to occlusive vascular disease. After controlling for major vascularrisk factors, diabetes roughly doubled occlusive vascularmortality risk among men (death rate ratio [RR] 2·10, 95% CI 1·97–2·24) and tripled risk among women (3·00, 2·71–3·33; χ 2 test for heterogeneity p Interpretation Independent of other major vascularrisk factors, diabetes substantially increased vascularrisk in both men and women. Lifestyle changes to reduce smoking and obesity and use of cost-effective drugs that target major vascularrisks (eg, statins and antihypertensive drugs) are important in both men and women with diabetes, but might not reduce the relative excess risk of occlusive vascular diseasein women with diabetes, which remains unexplained. Funding UK Medical Research Council, British Heart Foundation, Cancer Research UK, European Union BIOMED programme, and National Institute on Aging (US National Institutes of Health).