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Higher Blood Glucose Increases Stroke Risk in T2 Women but Not Men

Women disproportionately affected by stroke but cause is unknown….

Every year more than 795,000 people in the US have a stroke; 610,000 of these cases are first time or new strokes and about 185,000 are in people who have had a previous stroke. According to the CDC, blacks are two times more likely than whites to have a stroke. Diabetes greatly increases the risk of stroke; the health risk of cardiovascular disease is 2.5 times higher in diabetics compared to people without diabetes. Women are disproportionately affected by stroke, which is the fifth leading cause of death for men but the third leading cause for women.

Previous studies have shown that type 2 diabetes is a risk factor for stroke, but how gender might play into that is not clear. To find out, Dr. Wenhui Zhao, Dr. Gang Hu, and colleagues from Pennington Biomedical Research Center in Baton Rouge, La., turned to the Louisiana State University Hospital-Based Longitudinal Study. The analysis included 10,876 men and 19,278 women who had newly diagnosed type 2 diabetes and who were free from stroke or coronary heart disease at baseline.

Most of the patients were black (56% of men and 59% of women). Men had worse glycemic control than women at baseline (HbA1c 8.1% versus 7.6%).

During an average follow-up of 6.7 years, there were 2,949 strokes, with a higher rate among men. Despite the higher rate among men, however, glycemic control was related to stroke risk among women only.

Compared with women with a baseline HbA1c of 6% to 6.9%, women with values of 8% or higher had significantly increased risks of stroke during follow-up:

  • 8% to 8.9%: HR 1.19, 95% CI 1.00-1.42
  • 9% to 9.9%: HR 1.32, 95% CI 1.09-1.59
  • 10% or higher: HR 1.42, 95% CI 1.23-1.65

Every 1% increase in HbA1c at baseline among women was associated with a relative 5% increase in the risk of having a stroke during follow-up (HR 1.05, 95% CI 1.02-1.07), but the association was not significant among men, according to Hu.

A similar but weaker trend was seen when the researchers used updated HbA1c averages during follow-up.

The researchers speculated about why diabetes might be more detrimental for women, including the possibility that women have worse risk factor profiles such as higher blood pressure and lipid levels as compared to men.

"Others have suggested that the greater risk associated with diabetes seen in women may reflect a treatment bias that favors men," they wrote. "Several recent studies have found that men with diabetes or cardiovascular disease are more likely than women to receive aspirin, statins, or antihypertensive drugs."

They noted, however, that "in our study, after adjusting for systolic blood pressure, LDL cholesterol, and medication treatment, this graded association [between HbA1c and stroke] remained significant among females with type 2 diabetes."

Wenhui Zhao, MD, commented, "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."

The relationship was generally consistent in both black and white individuals and in both those who were and were not taking glucose-lowering medications; the stroke risks were also greater in women 55 and older, the researchers reported. "This is important to keep in mind when studying blood sugar level and other cardiovascular disease risk factors in the diabetic population and when planning a strategy to prevent cardiovascular disease, especially for women with type 2 diabetes," they wrote.

In terms of study limitations, the authors acknowledged that the findings might not be applicable to a population with a greater proportion of individuals with middle-to-high socioeconomic status, the stroke diagnoses were based on hospital discharge data and were not confirmed, and residual confounding could not be ruled out.

Practice Pearls:
  • Stroke kills almost 130,000 Americans each year; one out of every 19 deaths is stroke related.
  • Every 1% increase in HbA1c at baseline among women was associated with a relative 5% increase in the risk of having a stroke
  • Glycemic control was related to stroke risk among women only.

Zhao W, Katzmarzyk P, Horswell R, et al. Sex differences in the risk of stroke and HbA1c among diabetic patients. Diabetologia. 2014 Jan.