The following are 10 key points regarding sex differences in the cardiovascular (CV) consequences of diabetes mellitus (DM):

1. Increases in DM, most of which is type 2 DM (T2DM), have been observed in recent decades. In the United States, as of 2012, an estimated 29 million adults have DM, which translates into almost 30 million adults. The prevalence of T2DM is similar for men and women. CV disease (CVD) is the number one cause of morbidity and mortality among adults with DM. Unlike women without DM who have lower CVD rates than men, women with T2DM have similar rates of CVD to men with T2DM.
2. DM has been defined as equivalent to coronary heart disease (CHD) in prior guidelines. Women with T2DM have a three times increased risk for fatal CHD compared to women without T2DM, and a higher adjusted hazard ratio (HR) of fatal CHD in women with DM (hazard ratio [HR], 14.74; 95% confidence interval [CI], 6.16-35.27) compared with men with DM (HR, 3.77; 95% CI, 2.52-5.65). Furthermore, myocardial infarction occurs at an earlier age among women with DM compared to men.
3. Obesity may contribute to increased CVD risk among women with DM. Visceral adiposity (central obesity) differs by race/ethnicity such that understanding the implications of adipose depot is particularly important to understanding the influence of obesity among women with DM. For example, DM and CVD occur at lower body mass indexes and waist circumferences among Asian women compared to black or white women.
4. Development of hypertension (HTN), a major risk factor for CVD, is highly prevalent among adults with DM. Sex hormones may influence the impact of HTN on various organs such as the kidneys. Furthermore, conditions such as pre-eclampsia may influence the associations between blood pressure/HTN and CVD among women including women with DM.
5. For lipids, women tend to have higher high-density lipoprotein (HDL) cholesterol than men. However, among those with DM, HDL cholesterol is lower and there is some evidence to suggest the HDL particles have reduced anti-inflammatory effects, which may also vary by ethnicity.
6. Few studies have examined sex/gender-specific differences among patients with peripheral arterial disease and DM. However, some data suggest that women with peripheral arterial disease (PAD) and DM have increased post-surgical mortality after revascularization. In addition, women with DM and PAD may not improve in walking distance after exercise training compared to men or women with PAD, but no DM.
7. The prevalence of DM among male stroke patients appears higher than for female stroke patients. Risk factors for stroke also differ by sex. Studies differ regarding the strength of DM as a risk factor for men and women; however, a systematic review/meta-analysis of 64 cohorts observed that DM was a stronger risk factor for stroke in women compared to men. Women with DM had a 27% greater relative risk (RR) for stroke when baseline differences in other CV risk factors were taken into account compared to men (RR, 1.27; 95% CI, 1.10–1.46). Long-term survival is also reduced for stroke patients with DM.
8. Understanding the implications of gestational DM and polycystic ovarian syndrome may provide important clues to understanding the interaction of sex, DM, and CVD. Further research to examine the incidence of CVD in these conditions is warranted.
9. Understanding sex-specific differences in pharmacology is greatly needed. Differences in lipid-lowering medications among women with and without DM related to CV outcomes have been observed in prior studies, but not recent studies. Other medications including aspirin warrant further study in women (vs. men) with diabetes.
10. The authors recommend further research on sex/gender differences among different racial/ethnic groups, including additional research on the social and cultural factors, which may influence gender differences among adults with DM. Further research is also warranted on sex-specific differences of sex hormones in relation to CVD; as well as sex-specific differences of cardiac medications and glucose/insulin metabolism. Sex-specific analyses of lifestyle modification were also recommended.

Keywords: Adiposity, Aspirin, Blood Pressure, Cholesterol, HDL, Diabetes Mellitus, Type 2, Diabetes Mellitus, Ethnic Groups, Glucose, Gonadal Steroid Hormones, Hypertension, Lipoproteins, HDL, Myocardial Infarction, Obesity, Abdominal, Obesity, Peripheral Arterial Disease, Polycystic Ovary Syndrome, Primary Prevention, Risk Factors, Sex Characteristics, Stroke, Waist Circumference, Women

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