Sex Differences in Diabetes

by Brian Haverdink, NP

Editor's note: This column was developed with the Society for Women's Health Research (SWHR), the nation's only nonprofit organization whose mission is to improve the health of all women through research, education and advocacy. SWHR encourages the study of sex differences that affect the prevention, diagnosis and treatment of disease. Learn more at www.womenshealthresearch.org.

Diabetes is on the rise at an astonishing pace. More than 18 million U.S. residents now have diabetes.¹ Among people 20 years or older, approximately 9.3 million women and 8.7 million men are affected. Between 5% and 10% of women diagnosed with gestational diabetes develop type 2 diabetes immediately after pregnancy, and 20% to 50% will develop the disease in the next 5 to 10 years.² Children of women with gestational diabetes are more likely to become obese during childhood and have diabetes later in life.³

Susceptibility

In addition to the usual truncal obesity, sedentary lifestyle and family history, research shows that women's susceptibility to diabetes can be more complex. A study of obese patients found that one polymorphism in the promoter region of the uncoupling protein (UCP-2, a mitochondrial inner membrane protein) may be involved in obesity and type 2 diabetes. The genotype that causes increased transcription of UCP-2 mRNA was more prevalent in women with diabetes than in women without diabetes.⁴ No difference in distribution of this genotype was detected in men.

Endogenous sex hormones may be involved in the development of type 2 diabetes. In a prospective study of more than 500 women and men who did not have diabetes upon entry, diabetes was associated with low levels of total testosterone in men and high levels of bioavailable testosterone in women.⁵

Complications and Comorbidities

Cerebrovascular. The influence of diabetes on stroke risk is stronger in women than in men.^6-8 A significant difference in stroke risk has been documented in 55- to 64-year-old women with diabetes.⁶

Cardiovascular. In the past 30 years, deaths from coronary heart disease (CHD) have decreased in men with and without diabetes. However, CHD mortality has decreased only in women without diabetes.⁹ Although many studies indicate that women with diabetes are at greater CHD risk and mortality than men with diabetes, the relative risk varies among numerous studies.^6,10-14

In people with diabetes, the risk for myocardial infarction (MI) is greater in women than in men.^6,13,15 Among people with diabetes who have experienced MI, women have lower survival rates than men.² One year after MI, the mortality risk for women is higher than that for men.¹⁶ Women are more likely than men to have left ventricular hypertrophy, which strongly predicts cardiovascular morbidity and mortality.¹⁷ A study of hypertensive patients produced similar results.¹⁸

Vasculature. The adverse effects of diabetes on the vascular wall, including endothelial function, are greater in women with diabetes, further leading to atherogenesis and increased cardiovascular disease risk.^19-21 Sex differences in other diabetes-induced potentially adverse cardiovascular changes, such as abnormalities in waist-hip ratio, high-density lipoprotein (HDL) levels, apoliporotein B, fibrinogen and low-density lipoprotein (LDL), are also more prominent in women.^10,13 Women with diabetes are more susceptible to hypertension than men with diabetes, and family history of hypertension is a stronger factor for its development in women.^13,22

Glycemic Control. Among people with type 1 diabetes, women tend to have poorer glycemic control, lower basal insulin C-peptide and require a greater initial insulin dose.²³

Retinopathy. Women with diabetes are significantly more likely to have visual impairments, including blindness, than men with diabetes.³

Treatment and Management. Men with diabetes may achieve more favorable control of blood pressure and hyperglycemia than women with diabetes, particularly after age 60.²⁴ In Europe, women with diabetes are treated less often than men with certain life-saving therapies (acute reperfusion, beta-blockers, angiotensin-converting enzyme inhibitors, aspirin) after MI.^13,25,26

Putting Research in Perspective

What does this mean for our day-to-day practice? Instead of lumping patients with similar disease processes together, we need to carefully consider the influences of their biological sex. Being a woman or a man significantly affects prevention, the course of disease and the effectiveness of treatments.

References available online at http://www.advanceweb.com/np.

Brian Haverdink is a family nurse practitioner who practices at Hart Wellness in Hickory, N.C., and has a special clinical interest in women's health and men's health.