The prevalence of cardiometabolic multimorbidity (defined herein as a history of ≥2 of the following: diabetes mellitus, stroke, myocardial infarction [MI]) is increasing rapidly.^1-3 Considerable evidence exists about the mortality risk of having any 1 of these conditions alone.^4-7 However, evidence is sparse about life expectancy among people who have 2 or 3 cardiometabolic conditions concomitantly. Valid estimation of the associations of cardiometabolic multimorbidity with mortality requires comparison of people with multimorbidity with participants within the same cohorts who did not have any of the conditions at baseline. However, few population cohorts have had sufficient power, detail, and longevity to enable such comparisons.^8-14

Cardiovascular disease is among the leading causes of morbidity and mortality worldwide. Preventive treatment of high-risk asymptomatic individuals depends on accurate prediction of a person's risk to develop a cardiovascular event. Currently, cardiovascular risk prediction in asymptomatic individuals is based on the level of cardiovascular risk factors incorporated in scoring equations.¹ Several scores are available, with the Framingham Risk Score among the most widely used.^1,2 These risk equations perform reasonably well, yet there remains considerable overlap in estimated risk between those who are affected by a cardiovascular event and those who are not.³ Improvement in cardiovascular risk prediction is needed and may be established by including a measure of preclinical atherosclerosis in the risk prediction algorithms⁴ because atherosclerosis underlies the occurrence of cardiovascular events, develops over decades, and has a prolonged asymptomatic phase during which it is possible to modify the course of the disease.⁵

OBJECTIVE Type 2 diabetes confers a greater excess risk of cardiovascular disease in women than in men. Diabetes is also a risk factor for dementia, but whether the association is similar in women and men remains unknown. We performed a meta-analysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia. RESEARCH DESIGN AND METHODS A systematic search identified studies published prior to November 2014 that had reported on the prospective association between diabetes and dementia. Study authors contributed unpublished sex-specific relative risks (RRs) and 95% CIs on the association between diabetes and all dementia and its subtypes. Sex-specific RRs and the women-to-men ratio of RRs (RRRs) were pooled using random-effects meta-analyses. RESULTS Study-level data from 14 studies, 2,310,330 individuals, and 102,174 dementia case patients were included. In multiple-adjusted analyses, diabetes was associated with a 60% increased risk of any dementia in both sexes (women: pooled RR 1.62 [95% CI 1.45–1.80]; men: pooled RR 1.58 [95% CI 1.38–1.81]). The diabetes-associated RRs for vascular dementia were 2.34 (95% CI 1.86–2.94) in women and 1.73 (95% CI 1.61–1.85) in men, and for nonvascular dementia the RRs were 1.53 (95% CI 1.35–1.73) in women and 1.49 (95% CI 1.31–1.69) in men. Overall, women with diabetes had a 19% greater risk for the development of vascular dementia than men (multiple-adjusted RRR 1.19 [95% CI 1.08–1.30]; P < 0.001). CONCLUSIONS Individuals with type 2 diabetes are at ∼60% greater risk for the development of dementia compared with those without diabetes. For vascular dementia, but not for nonvascular dementia, the additional risk is greater in women.

A previous pooled analysis suggested that women with diabetes are at substantially increased risk of fatal CHD compared with affected men. Additional findings from several larger and more contemporary studies have since been published on the sex-specific associations between diabetes and incident CHD. We performed an updated systematic review with meta-analysis to provide the most reliable evidence of any sex difference in the effect of diabetes on subsequent risk of CHD. PubMed MEDLINE was systematically searched for prospective population-based cohort studies published between 1 January 1966 and 13 February 2013. Eligible studies had to have reported sex-specific RR estimates for incident CHD associated with diabetes and its associated variability that had been adjusted at least for age. Random-effects meta-analyses with inverse variance weighting were used to obtain sex-specific RRs and the RR ratio (RRR) (women:men) for incident CHD associated with diabetes. Data from 64 cohorts, including 858,507 individuals and 28,203 incident CHD events, were included. The RR for incident CHD associated with diabetes compared with no diabetes was 2.82 (95% CI 2.35, 3.38) in women and 2.16 (95% CI 1.82, 2.56) in men. The multiple-adjusted RRR for incident CHD was 44% greater in women with diabetes than in men with diabetes (RRR 1.44 [95% CI 1.27, 1.63]) with no significant heterogeneity between studies (I ² = 20%). Women with diabetes have more than a 40% greater risk of incident CHD compared with men with diabetes. Sex disparities in pharmacotherapy are unlikely to explain much of the excess risk in women, but future studies are warranted to more clearly elucidate the mechanisms responsible for the substantial sex difference in diabetes-related risk of CHD.