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Do Cardiovascular Risks Differ for Men and Women with or without Diabetes?

Type 2 diabetes is associated with greater relative risk of CHD in women than in men, according to The British Regional Heart Study and British Women’s Heart Health Study.

This study combined data from the British Regional Heart Study and the British Women’s Heart Health Study to assess whether cardiovascular risk factors differ more between women with and without diabetes than between men with and without diabetes. The sample was 3752 men (11.1% with diabetes) and 3777 women (9.5% with diabetes) aged 60-79 years with no previous myocardial infarction. The researchers explored several conventional and novel cardiovascular risk factors, such as markers of insulin resistance, inflammation, activated coagulation, and endothelial dysfunction. Comparisons between patients with and without diabetes were conducted separately for men and women. Data were then combined to test for an interaction between sex and diabetes in their association with the risk factors.

Overall, women without diabetes tended to have more favorable risk factors and were less insulin-resistant than men without diabetes, but differences between men and women were much smaller or absent in the presence of diabetes. Furthermore, the relative differences in several risk factors between patients with and without diabetes were much greater among women. For example, waist circumference was 4.7 cm greater in men with diabetes than in those without diabetes (101.3 cm vs 96.6 cm; P < .001) but 8.2 cm greater in women with diabetes than in those without diabetes (93.5 cm vs 85.3 cm; P < .001), and the interaction between diabetes and sex was highly significant (P < .001).

Body mass index; leukocyte count; homeostatic model assessment of insulin resistance (HOMA-IR); diastolic blood pressure; and levels of high-density lipoprotein cholesterol, tissue plasminogen activator, and factor VIII all differed more between women with and without diabetes than between men with and without diabetes (test for diabetes/sex interaction P < .05). The more adverse effect of diabetes on these risk markers in women was associated with insulin resistance: Men and women with diabetes had similar HOMA-IR (5.93 vs 5.98; P = .96), but the diabetes/sex interaction was highly significant (P < .01).

Several studies have reported that the effect of diabetes on cardiovascular risk is greater in women than men. Indeed, it has long been reported that the relative effect in women may be sufficient to eliminate the inherent cardiovascular disease benefit in women. However, the reasons for the apparent greater effect of diabetes on cardiovascular disease among women are not clear.

The current study found that the greater difference in risk factors between women with and without diabetes relative to men was largely explained by greater changes in adiposity and insulin resistance in women than in men. The investigators conclude that women apparently undergo more profound metabolic changes to develop diabetes than do men. That logic suggests that diabetes diagnostic criteria may need to be different for men and women. We know that men typically have higher fasting plasma glucose levels than women. It follows, therefore, that a woman would have to increase her fasting plasma glucose level more than a man to reach the diagnostic threshold. This greater increase would presumably be the result of greater insulin resistance, as the current study suggests. If so, and we want to define diabetes by some “constant” measure of metabolic dysfunction, then using a “constant” measure of compensatory hyperglycemia does not seem to be the correct approach.

Wannamethee SG, Papacosta O, Lawlor DA, et al Diabetologia. 2012;55:80-87