Elsevier

The Lancet

Volume 383, Issue 9933, 7–13 June 2014, Pages 1973-1980
The Lancet

Articles
Diabetes as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 64 cohorts, including 775 385 individuals and 12 539 strokes

https://doi.org/10.1016/S0140-6736(14)60040-4Get rights and content

Summary

Background

Diabetes mellitus is a major cause of death and disability worldwide and is a strong risk factor for stroke. Whether and to what extent the excess risk of stroke conferred by diabetes differs between the sexes is unknown. We did a systematic review and meta-analysis to estimate the relative effect of diabetes on stroke risk in women compared with men.

Methods

We systematically searched PubMed for reports of prospective, population-based cohort studies published between Jan 1, 1966, and Dec 16, 2013. Studies were selected if they reported sex-specific estimates of the relative risk (RR) for stroke associated with diabetes, and its associated variability. We pooled the sex-specific RRs and their ratio comparing women with men using random-effects meta-analysis with inverse-variance weighting.

Findings

Data from 64 cohort studies, representing 775 385 individuals and 12 539 fatal and non-fatal strokes, were included in the analysis. The pooled maximum-adjusted RR of stroke associated with diabetes was 2·28 (95% CI 1·93–2·69) in women and 1·83 (1·60–2·08) in men. Compared with men with diabetes, women with diabetes therefore had a greater risk of stroke—the pooled ratio of RRs was 1·27 (1·10–1·46; I2=0%), with no evidence of publication bias. This sex differential was seen consistently across major predefined stroke, participant, and study subtypes.

Interpretation

The excess risk of stroke associated with diabetes is significantly higher in women than men, independent of sex differences in other major cardiovascular risk factors. These data add to the existing evidence that men and women experience diabetes-related diseases differently and suggest the need for further work to clarify the biological, behavioural, or social mechanisms involved.

Funding

None.

Introduction

Diabetes mellitus is a global health concern; an estimated 347 million people worldwide are affected, and in 2008 diabetes accounted for 1·3 million deaths.1, 2, 3 The incidence of diabetes is projected to increase by more than 50% in the next decade because of rapid increases in the prevalence of obesity and physical inactivity. As a result, diabetes is predicted to become the seventh leading cause of death in the world by 2030.3, 4

The burden of diabetes as a major cause of premature illness and death is mostly caused by the associated increased risk of cardiovascular disease. Widely quoted estimates from WHO suggest that the cardiovascular risk in people with diabetes is two to three times higher than in those without the disease, and that cardiovascular diseases cause between 50% and 80% of deaths in people with diabetes.3 However, these estimates are based on the assumption that diabetes confers the same degree of risk in women as in men, which is unlikely to be correct in view of the accruing evidence that women and men experience the disease differently.4, 5 Indeed, we have previously shown that the relative risk (RR) of diabetes-related coronary heart disease is substantially higher in women than in men, even after differences in other major cardiovascular risk factors have been taken into account.6 Whether this sex difference also exists for stroke—which shares many of the same risk factors—remains uncertain. Findings from previous studies have been inconsistent, with some investigators reporting either a stronger,7, 8 similar,9 or weaker effect of diabetes on stroke risk in women compared with men.10, 11

In view of the substantial implications that any clinically important sex difference in the association between diabetes and stroke risk would have, we did a systematic review and meta-analysis of all available prospective data to estimate the relative effect of diabetes on stroke risk in women compared with men.

Section snippets

Search strategy and selection criteria

We systematically searched PubMed for reports published between Jan 1, 1966, and Dec 16, 2013, using a combined text and MeSH heading search strategy with the terms: “diabetes mellitus”, “diabetes”, “prediabetes”, “impaired fasting glucose”, “impaired glucose intolerance”, “borderline diabetes,” “blood glucose”, “hemoglobin A, glycosylated”, “cohort studies”, “sex”, “gender”, “cardiovascular disease”, “stroke”, “cerebrovascular disease”, “cerebrovascular attack”, “cerebral ischemia”, “brain

Results

The systematic search identified 6120 articles, which were assessed by title and abstract. Of these, 92 articles qualified for selection (figure 1). After full-text assessment, 12 studies provided published, and one study unpublished, summary data for sex differences in the association between diabetes and risk of stroke.7, 8, 9, 10, 11, 20, 21, 22, 23, 24, 25, 26, 27, 28 This database was extended with individual participant data from APCSC, ARIC, NHANES III, and SHHEC.12, 13, 14, 15

Table 1

Discussion

In this pooled analysis of 64 cohorts, with data for more than three-quarters of a million individuals and more than 12 000 fatal and non-fatal stroke events, diabetes was a stronger risk factor for stroke in women than in men. Compared with men with diabetes, women with diabetes had a 27% greater RR for stroke when baseline differences in other major cardiovascular risk factors were taken into account. This sex difference in diabetes-related stroke risk was apparent and consistent across a

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