Do women exhibit greater differences in established and novel risk factors between diabetes and non-diabetes than men? The British Regional Heart Study and British Women’s Heart Health Study

Abstract

Aims/hypothesis Type 2 diabetes is associated with greater relative risk of CHD in women than in men, which is not fully explained by conventional cardiovascular risk factors. We assessed whether cardiovascular risk factors including more novel factors such as markers of insulin resistance, inflammation, activated coagulation and endothelial dysfunction differ more between diabetic and non-diabetic women than between diabetic and non-diabetic men, and the role of insulin resistance. Methods A cross-sectional study of non-diabetic and diabetic men and women (n=7,529) aged 60-79 years with no previous myocardial infarction who underwent an examination was conducted. Measurements of anthropometry, blood pressure and fasting measurements of lipids, insulin, glucose and haemostatic and inflammatory markers were taken. Results Non-diabetic women tended to have more favourable risk factors and were less insulin resistant than nondiabetic men, but this was diminished in the diabetic state. Levels of waist circumference, BMI, von Willebrand factor (VWF), WBC count, insulin resistance (HOMA-IR), diastolic blood pressure, HDL-cholesterol, tissue plasminogen activator (t-PA) and factor VIII differed more between diabetic and non-diabetic women than between diabetic and non-diabetic men (test for diabetes×sex interaction p< 0.05). The more adverse effect of diabetes on these risk markers in women was associated with, and thereby largely attenuated by, insulin resistance. Conclusions/interpretation The greater adverse influence of diabetes per se on adiposity and HOMA-IR and downstream blood pressure, lipids, endothelial dysfunction and systemic inflammation in women compared with men may contribute to their greater relative risk of coronary heart disease.

Type 2 diabetes from pediatric to geriatric age: analysis of gender and obesity among 120 183 patients from the German/Austrian DPV database

“…T2DM manifested in men at comparatively lower BMI values than in females, indicating male-female BMI risk profile differences. Similar findings have been reported in other studies (23,24). In patients older than 80 years, there was a decline in BMI, both in the diabetic group and in the general population, possibly reflecting the influence of malnutrition and frailty.…”

“…Possible reasons for these gender differences include the fact that older women have adverse changes in inflammatory processes and biomarkers (e.g. von Willebrand factor or tissue plasminogen activator) than same-aged men, which favor the development of insulin resistance and exacerbate CVD risk (23,29). Furthermore, older women have higher sphingolipid concentrations than men (30), suggesting increased influences of sphingolipid metabolite concentrations on insulin resistance and subsequent risk of CVD in the face of obesity.…”

ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD – Summary

“…A recent study revealed a greater adverse influence of DM on adiposity, homeostatic model assessment-insulin resistance (HOMA-IR) and downstream blood pressure, lipids, endothelial dysfunction, and systemic inflammation in women than in men, which may contribute to their greater relative risk of CAD. 32 Also, it seems that women put on more weight before developing diabetes and consequently undergo bigger changes in risk factor status. 33 …”

Incident diabetes mellitus may explain the association between sleep duration and incident coronary heart disease

“…However, there is emerging evidence of the importance of sex-stratification in research involving diabetes-related risk factors [18,19] and outcomes [17,20].…”