Increased risk of stroke in women but not men with high HbA1c

Zhao W, Katzmarzyk PT, Horswell R et al.,
Diabetologia Feb 24 2014 DOI 10.1007/s00125-014-3190-3

Background

Sex differences in stroke have been observed in epidemiological studies, pathophysiology, treatment and outcome. These differences impact effective prevention and treatment of stroke.
Type 2 diabetes is known to be an independent risk factor for stroke [1-5], but it is unclear how much this effect is affected by gender.
Randomised clinical trials (RCTs) and meta-analysis have failed to show the benefit of intensive glucose control on rates of stroke [6]. Often, females are underrepresented in RCTs [7], thus there is a need for more observational data to assess whether there is a sex-specific association between HbA1c and the risk of stroke. The present study examined that association in men and women with type 2 diabetes, without a history of stroke (mean follow-up period 6.7 years).

Main findings

• The overall incidence of stroke was higher in men (16.0/1000 person-years) than women (13.9/1000 person-years).
• Baseline HbA1c was significantly and positively associated with stroke risk among females but not males. This association remained significant in women after correction for confounding factors. Each 1% increase in baseline HbA1c was associated with 5% increased (95%CI: 1.02-1.07) risk of stroke in females and 1% increased (95%CI: 0.99-1.04) risk in men (P for interaction= 0.005).
• The association of HbA1c with stroke risk was seen in diabetic female patients irrespective of whether or not they took glucose-lowering agents, and both in African-American and white patients.
• When stratified by age, each 1% increase in baseline HbA1c was associated with a 2% higher (95%CI: 1.00-1.05) stroke risk in women younger than 55 years, and with a 5% increased (95%CI: 0.99-1.04) risk in females over 55 years old.
• Each 1% increase in follow-up HbA1c was associated with a 3% higher (95%CI: 1.00-1.06) risk of stroke in females and 3% higher (95%CI: 0.99-1.07) risk in males.

Conclusion

This study shows that HbA1c is statistically significantly associated with risk of stroke in female but not male patients with type 2 diabetes, most pronounced in women over 55 years of age. The graded positive association was seen in both African American and white females, and in women who were or were not taking glucose-lowering medication.
It should be noted that many of the individuals in this study were uninsured and with low socioeconomic status, so it is possible that generalisability to a middle or high socioeconomic status population is limited.

Find this article online

References

1. Wannamethee SG, Perry IJ, Shaper AG (1999) Nonfasting serum glucose and insulin concentrations and the risk of stroke. Stroke 30: 1780–1786
2. Almdal T, Scharling H, Jensen JS et al. (2004) The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death: a population-based study of 13,000 men and women with 20 years of follow-up. Arch InternMed 164:1422–1426
3. Sarwar N, Gao P, Seshasai SR et al (2010) Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375:2215–2222
4. Hu G, Jousilahti P, Sarti C, et al. (2006) The effect of diabetes and stroke at baseline and during follow-up on stroke mortality. Diabetologia 49:2309–2316
5. Hu G, Sarti C, Jousilahti P et al (2005) The impact of history of hypertension and type 2 diabetes at baseline on the incidence of stroke and stroke mortality. Stroke 36:2538–2543.
6. Macisaac RJ, Jerums G (2011) Intensive glucose control and Cardiovascular outcomes in type 2 diabetes. Heart Lung Circ 20:647–654
7. Melloni C, Berger JS, Wang TY et al (2010) Representation of women in randomized clinical trials of cardiovascular disease prevention. Circ Cardiovasc Qual Outcomes 3:135–142