New research published in Diabetologia (the journal of the European Association for the Study of Diabetes) shows that diabetes in women is associated with an increased risk of stroke, whereas the data do not show the same association among men. The research is by Dr Wenhui Zhao (the first author), Dr Gang Hu and colleagues at the Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
Differences in incidence and mortality between sexes have been reported for various conditions, including stroke. More women than men tend to die from stroke in developed countries. For example, in the USA, 77,109 women and 52,367 men died from stroke in 2010. Women accounted for almost 60% of US stroke deaths in 2010. In the UK, 32,828 women and 20,358 men died from stroke in 2007.
The authors prospectively investigated the sex-specific association of different levels of HbA1c with incident stroke risk among 10,876 male and 19,278 female patients with type 2 diabetes in the Louisiana State University Hospital-Based Longitudinal Study (LSUHLS). During a mean follow up of 6.7 years, 2,949 incident cases of stroke were identified. The authors calculated the risk of stroke associated with different levels of HbA1c at baseline (<6.0%, 6.0 .9% [reference group, considered normal blood sugar control], 7.0 .9%, 8.0 .9%, 9.0 .9%, and ≥10.0%). Among men, although there was a trend towards increased risk of stroke as HbA1c increased, this increased risk was not statistically significant. Among women, however, those with HbA1c of 8.0 .9% were 19% more likely to have a stroke than the normal blood sugar reference group women; those with 9.0 .9% HbA1c were 32% more likely to have a stroke, and those above 10% HbA1c were 42% more likely to have a stroke, with each of these associations statistically significant.
Even when the data were adjusted by race, and whether or not anti-diabetic drugs were used by the women, this graded association of HbA1c with stroke in women was still present. When adjusted by age, the researchers found the risk of stroke among diabetic women was substantially raised for women aged 55 years and over compared with younger women.
Worldwide, stroke is more common among men, but women with stroke appear to become more severely ill following a stroke. These sex differences have profound implications for effective prevention and treatment of stroke. Thus the increased knowledge of stroke risk factors in the population, such as that provided by this study, may lead to improved prevention of stroke.
"Several mechanisms could explain why diabetes has a greater adverse effect in women than in men. In the general population, higher numbers of strokes occurring among women than men is at least partly attributed to the longer life expectancy of women," explains Dr Zhao. "Some studies have suggested that the sex difference in cardiovascular risk is mediated in large part by differences in the levels of cardiovascular risk factors because women with diabetes have significantly higher levels of blood pressure and lipids than men with diabetes. Others suggested that the greater risk associated with diabetes seen in women may reflect a treatment bias that favours men. Recent studies found that men with diabetes or established cardiovascular disease are more likely to receive aspirin, statins, or antihypertensive drugs than women."
Referring to the increased risk of stroke in diabetic women aged 55 years and over, Dr Hu says: "This might suggest that poor blood glucose control is more harmful in elderly women than in younger ones. The possible explanation may point to the role for oestrogen. After onset of menopause, when oestrogen levels decline, the incidence of cerebrovascular disease in women increases. Pre-clinical (animal) studies have indicated that oestrogen is neuroprotective and reduces stroke infarct volume, but clinical trials failed to show the benefit. There is a need for more research to clarify this association."
He also adds that the lack of an association between HbA1c and stroke risk in men with type 2 diabetes in the present study could be due to men with higher HbA1c values dying from coronary heart disease, rather than having a stroke.
Dr Hu concludes: "Diabetes poses a substantially greater increase in the risk of stroke among women than among men which merits further investigation. This graded positive association was more significant in women 55 years and older than in women younger than 55 years. Females with type 2 diabetes, especially postmenopausal females, are at high risk for stroke. More aggressive blood sugar treatments and better control of other risk factor levels in women with diabetes are likely to substantially reduce stroke in this subgroup."
- Wenhui Zhao, Peter T. Katzmarzyk, Ronald Horswell, Yujie Wang, Jolene Johnson, Gang Hu. Sex differences in the risk of stroke and HbA 1c among diabetic patients. Diabetologia, February 2014 DOI: 10.1007/s00125-014-3190-3
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