ArticlesDiabetes 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
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
References (52)
- et al.
National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants
Lancet
(2011) - et al.
IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030
Diabetes Res Clin Pract
(2011) - et al.
Cigarette smoking as a risk factor for coronary heart disease in women compared with men: a systematic review and meta-analysis of prospective cohort studies
Lancet
(2011) - et al.
A comparison of risk factors for coronary heart disease and ischaemic stroke: the Dubbo study of Australian elderly
Heart Lung Circ
(2009) - et al.
Sex-specific differences in glycemic control and cardiovascular risk factors in older patients with insulin-treated type 2 diabetes mellitus
Gend Med
(2010) - et al.
Cardiovascular risk in women with diabetes
Nutr Metab Cardiovasc Dis
(2010) - et al.
The clinical reality of guidelines for primary prevention of cardiovascular disease in type 2 diabetes in Italy
Atherosclerosis
(2008) - et al.
Women show worse control of type 2 diabetes and cardiovascular disease risk factors than men: from the MIND.IT Study Group of the Italian Society of Diabetology
Nutr Metab Cardiovasc Dis
(2013) - et al.
Oxidized lipids in insulin-dependent diabetes mellitus: a sex-diabetes interaction?
Metabolism
(1994) - et al.
Gender differences in insulin resistance, body composition, and energy balance
Gend Med
(2009)
Diabetes (fact sheet No312)
Taking sex into account in medicine
Lancet
Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies
BMJ
Diabetes mellitus and risk of stroke and its subtypes among Japanese: the Japan public health center study
Stroke
Sex differences in cardiovascular and total mortality among diabetic and non-diabetic individuals with or without history of myocardial infarction
Diabetologia
Incidence and risk factors for subtypes of cerebral infarction in a general population: the Hisayama study
Stroke
The impact of diabetes on coronary heart disease differs from that on ischaemic stroke with regard to the gender
Cardiovasc Diabetol
Impact of glucose tolerance status on development of ischemic stroke and coronary heart disease in a general Japanese population: the Hisayama study
Stroke
Adding social deprivation and family history to cardiovascular risk assessment: the ASSIGN score from the Scottish Heart Health Extended Cohort (SHHEC)
Heart
Plan and operation of the Third National Health and Nutrition Examination Survey, 1988–94. Series 1: programs and collection procedures
Vital Health Stat 1
Cohort profile: the Asia Pacific Cohort Studies Collaboration
Int J Epidemiol
The Atherosclerosis Risk in Communities (ARIC) study: design and objectives
Am J Epidemiol
Epidemiology: study design and data analysis
Quantifying heterogeneity in a meta-analysis
Stat Med
Measuring inconsistency in meta-analyses
BMJ
Cited by (564)
Sex and stroke risk factors: A review of differences and impact
2024, Journal of Stroke and Cerebrovascular DiseasesDiabetes and women, why are we different?
2024, SemergenStrong independent association between third-degree AV-block and diabetes mellitus using a large database
2023, Diabetes Research and Clinical PracticeLong chain n-3 polyunsaturated fatty acid intake across the life span for cardiovascular disease prevention in women
2024, Proceedings of the Nutrition Society