Women and diabetes – questions on gender-specific impact

According to the World Health Organization’s ‘Global Report on Diabetes’ 2016, diabetes is directly responsible for 1.5 million deaths around the world. This makes it the eighth leading cause of mortality. However, its impact is higher in women, for who diabetes is the fifth leading cause of death. At present, more than 200 million women are estimated to live with diabetes.
One reason for the problem of diabetes in women is the rise in the number of patients with the disease. The prevalence of diabetes, according to the WHO, has doubled since 1980. Moreover, it is no longer a disease that largely affects rich nations. Indeed, prevalence is now growing quickest in middle-income countries. More than half of the total number of women with diabetes today live in southeast Asia and the Western Pacific.
Another issue here is the the lack of healthcare. This means that the management of diabetes is inadequate, particularly for poorer people.

Debate dates to end of 1990s
The debate about gender and diabetes began to intensify at the end of the 1990s, as epidemiology improved, especially outside Western countries.
In January 2001, a report by University of Bristol researchers in ‘Diabetologia’ found geography and gender to be a major factor in Type I diabetes. The report found an excess of male patients in regions with the highest incidence of diabetes, above all in populations of European origin. These showed a roughly 3:2 ratio of males to females in the 15-40 age group. On the other side of the equation, lowest risk populations for Type I diabetes (principally non-European) typically showed a female bias.
The Bristol researchers also observed that Type II diabetes had shown an excess of females in the first half of the 20th century but had become equally prevalent among men and women in most populations, with some evidence of male preponderance in early middle age. Men seemed to also be more susceptible than women “to the consequences of indolence and obesity, possibly due to differences in insulin sensitivity and regional fat deposition.”  In addition, women were more likely to transmit Type II diabetes to their offspring.

Geography and gender
Recent figures from the WHO on mortality from high glucose confirm the dual impact of gender and geography. The data shows a fork in female mortality, from near equivalence to males in the Eastern Mediterranean, Africa and the Western Pacific, to  being about three fourths of male mortality in Europe, the Americas and South-East Asia.
Women may also be more prone to dying from diabetes due to physiological factors. Data show that women with diabetes are more likely than male patients to have poor blood glucose control and be overweight, along with high blood pressure and cholesterol levels. The latter impact directly on cardiac risk factors, and do so in seemingly different ways for men and women.
Male death rates fall, women’s stays unchanged
In 2007, a study in the ‘Annals of Internal Medicine’ revealed a disturbing fact – that women with diabetes fared far worse than men. The study found that in 1971-2000, death rates for diabetic men fell, while the rate for women hardly changed. Worse, while men with diabetes lived on average for 7.5 fewer years than those who did not have the disease, the difference for women was 8.2 years. This disparity is probably due to a combination of multiple factors, according to the study.

Physiological factors and standards of treatment
Most factors are physiological. However, it seems outcomes for women with diabetes may also be worse due to differences in standards of care and treatment. Some of these were highlighted in 2005 in ‘Diabetes Care’, or two years before the ‘Annals of Internal Medicine’ study mentioned above.
The ‘Diabetes Care’ article covered risk factors in coronary heart disease (CHD) and treatment for Type II diabetes. It found that women with diabetes “received less treatment for many modifiable CHD risk factors than diabetic men.” This included staple therapies such as medication for high LDL cholesterol. The authors concluded that “more aggressive treatment of CHD risk factors” in women offered “a specific target for improvement in diabetes care.”
In 2010, a study in ‘Diabetic Medicine’ found the picture to be similar for Type I diabetes. The study by another Massachusetts General Hospital team, led by M.E Clarkin, found women reported lower use than men of medications to reduce CHD risk. These included glycated hemoglobin, as well as aspirin, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) and statins.

The role of cardiac health
Key physiological differences do indeed concern cardiac health.
In the general population, women tend to live longer than men, mainly because of lower rates of heart disease. However, such an advantage becomes insignificant for diabetic women. Indeed, the risk of heart disease is reported to be six times higher for women with diabetes than those without, compared to an increase of just 2-3 times in men.
This impacts directly on mortality for several reasons. One of the most significant is that women can have heart attacks without its most notable symptom in males, namely chest pain. Indeed, women are more likely to experience only nausea, shortness of breath, and back or jaw pain during a heart attack. Many women and medical practitioners in poorer parts of the world do not recognize the latter as warning signs. This lowers the chance of recovery.
One study published in the ‘European Heart Journal’ in 2007 found a stronger association between diabetes and death by heart failure for women than men. A Finnish study also found that heart attacks are more often fatal for women with diabetes than they are for men.
Indeed, perception is linked to less effective health care for women with diabetes, and this is best typified by cardiac health. As women are less likely to have heart attacks than men, a woman may not raise the same alarm bells as a man, especially when she does not experience chest pain.

Renal disease
Women with diabetes face complications from renal disease, too. Men have a higher risk for kidney disease, but this disappears with the onset of diabetes. Women with diabetes are just as likely to get kidney disease as men. Moreover, such a likelihood is not dependent on age, although women tend to be unaffected by kidney disease until menopause, when a drop in oestrogen levels makes the female endocrine system more like a male’s. 
Some studies have found that lower oestrogen levels are associated with kidney disease, but the mechanisms of this association are not yet clear. One theory is that high testosterone, which kicks in as estrogen levels drop, is responsible. Should this be proven clinically, it may be possible for women with diabetes to use hormone therapy to restore the balance between estrogen and testosterone, and thereby improve their kidney health.

Mental health
Depression is about twice as common in women as men and is believed to worsen the outlook for women with diabetes. A study of women in the ‘Archives of Internal Medicine’ in 2010 suggests a two-way relationship between depression and diabetes risk, with each influencing the other. Indeed, some women-only studies have shown women with both conditions are twice as likely to die early as those who had neither. In 2006, a study in ‘Public Health’ extended the scope to men and found that diabetes and depression were not associated in men, unlike in women.

Polycystic ovary syndrome
Women with diabetes are also likely to have several conditions which are female-specific.
One of these is polycystic ovary syndrome (PCOS), a metabolic disorder caused by hormonal imbalance in the female body. PCOS causes irregular periods and can result in fertility problems. It is also associated with acne, darkening of facial skin and hair growth on the face, loss of hair on the head etc. Females with PCOS are at heightened risk of getting diabetes, and the above signs are thus potential indicators of impending diabetes.
The precise mechanism of PCOS is not known, but there is clinical evidence that women with PCOS develop high levels of resistance to insulin and this then leads to development of Type II diabetes.
What has however been confirmed is that women diagnosed with PCOS at an early age show a higher risk of diabetes and fatal heart conditions later in life.

Gestational diabetes mellitus
Women also face the risk of gestational diabetes mellitus (GDM). This is defined as blood glucose values above normal but below those of diabetes. GDM is diagnosed through screening, since several of its symptoms such as increased thirst and urination needs, dry mouth and fatigue are commonplace in pregnancy and are not necessarily a sign of a problem.
Although the true prevalence of GDM is unknown, it is estimated to affect 1-14% of pregnancies in the US, depending on the population studied and the diagnostic tests used. Recent research has focused on high-risk groups. A pan-European study of women with body mass index greater than 29 kg/m2  found prevalence of 24% in early pregnancy, with another 14% developing GDM at mid gestation (24-28 weeks) and 13% at late gestation (35-37 weeks). The study was published in the October 2017 issue of ‘Diabetologia’ and covered women at 11 centres across Europe.
GDM increases the risk of certain complications during pregnancy and delivery, both for the women in question and for their infants. One of these is pre-eclampsia, which causes high blood pressure during pregnancy. Others include the baby growing larger than usual and polyhydramnios, which is the presence of excess amniotic fluid.
Though GDM is a temporary condition, affected women have an over-sevenfold increase in the risk of developing Type II diabetes 5-10 years after delivery. Moreover, children born to mothers with GDM are also more likely to develop impaired glucose tolerance.
Early diagnosis of GDM through testing for blood sugar and modifications to lifestyle can be effective in preventing or delaying the condition and treating its consequences.