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Metabolic dysfunction is a root cause of many chronic diseases plaguing Americans today, including obesity, diabetes, heart disease, stroke, and dementia. But there is a growing body of evidence that a number of the consequences of poor metabolic health hit women harder than men.
Statistics show that by the age of 45, women are more likely than men to be overweight or have obesity, a significant risk factor for diabetes. Women are also more likely to have impaired glucose tolerance throughout their lifetime.
Several factors are responsible for these differences, including genetics, body fat distribution, BMI, history of gestational diabetes, and balance of sex hormones. Studies show women are also more likely to experience sleep disturbance and insomnia, as well as higher levels of stress, all of which are linked to an increased risk of metabolic disease.
Furthermore, many issues affecting women’s health can have roots in poor blood sugar control and insulin resistance. These include polycystic ovarian syndrome (PCOS), infertility, menstrual dysfunction, menopausal symptoms, weight management, and even skin health.
Here, we break down the many ways in which metabolic health directly impacts women’s health.
PCOS and Infertility
The Metabolic Link: PCOS is a leading cause of infertility, and women with PCOS are more likely to be insulin resistant and develop diabetes.
The Science: PCOS is a hormonal disorder that is the most common cause of female infertility. According to the Centers for Disease Control and Prevention (CDC), PCOS affects 6 to 12 percent of US women of reproductive age, or as many as 5 million people. The exact cause of PCOS is unknown, but a mixture of genetics and lifestyle may play a role.
PCOS is a condition of hormonal imbalance, so symptoms vary widely. They can include irregular menstrual cycles, obesity, infertility, increased levels of male hormones, thinning scalp hair, excess body hair, acne, and many small follicles, or collections of cells enveloping fluid, on the ovaries. In addition, PCOS has metabolic consequences: Research shows as many as 70 percent of women with PCOS have insulin resistance. The CDC reports that more than half of women with PCOS develop Type 2 diabetes by age 40.
While it is not entirely clear why insulin resistance affects so many women with PCOS, it likely involves a combination of genetics, diet, and lifestyle factors.
But exactly how do these high insulin levels affect PCOS and infertility? Excess insulin in the body stimulates the theca cells of the ovaries to produce excess “masculine” hormones (called androgens), including testosterone, which leads to many of the symptoms of PCOS-like infertility and hair growth. Some research shows that women with PCOS and high levels of androgens have higher blood glucose levels than women with PCOS who have lower androgen levels.
And while excess insulin can spur increases in androgens, high androgen levels can also worsen insulin resistance in several ways, including lowering levels of adiponectin, an insulin-sensitizing hormone, and impairing insulin activity in muscle and fat cells.
What You Can Do: The good news is that diet and lifestyle changes can make a difference for many women. One study showed that 24 weeks on a low-glycemic diet improved insulin sensitivity and lowered fasting insulin for women with PCOS. Other studies have demonstrated similar effects.
The Menstrual Cycle and Blood Sugar Levels
The Metabolic Link: Fluctuations in estrogen and progesterone hormones during the menstrual cycle impact glucose metabolism and insulin sensitivity. In general, researchers believe estrogen promotes insulin sensitivity, while progesterone promotes insulin resistance.
The Science: The menstrual cycle has two phases: the follicular, or pre-ovulation phase, and the luteal, or post-ovulation phase. The luteal phase is characterized by increased estrogen and progesterone as the body prepares for fertilization, and then a drop in both before menstruation if no fertilization occurs. The follicular phase generally has lower progesterone levels and an uptick in estrogen at the end.
Studies show that glucose concentrations tend to be higher in the luteal phase than in the follicular phase, as the higher levels of progesterone decrease insulin sensitivity, which means insulin is not as efficient at clearing glucose from your blood, leading to higher levels.
On the other hand, estrogen has many beneficial metabolic effects, including improving the expression of insulin signaling molecules in skeletal muscles (in animal models) and lowering visceral fat and improving insulin sensitivity in women.
Some studies also find that fasting insulin rises before ovulation, reaching a height during the luteal phase. This adds weight to the studies demonstrating lower insulin sensitivity during the luteal phase.
What You Can Do: Given this research, it makes sense to avoid high-carb foods and instead focus on low-glycemic ingredients during the luteal phase to minimize elevated blood sugar levels and spikes.
Related article: How does the menstrual cycle affect blood sugar levels?
Hot Flashes and Other Menopausal Symptoms
The Metabolic Link: Research shows a relationship between high blood sugar levels and menopausal symptoms: Diabetes and insulin resistance appear to make them worse.
The Science: Up to 80 percent of women undergoing natural menopause experience hot flashes, and about 30 percent say they have frequent or severe symptoms. The medical term for hot flashes is vasomotor episodes since the constriction and dilation of blood vessels appear to play a role. Research shows that ovarian changes in early menopause that cause drops in estrogen bring on the hot flash symptoms.
Several extensive longitudinal studies suggest a link between incidence and severity of hot flashes and impaired glucose control.
For example, one study that followed about 150,000 postmenopausal women for more than 20 years found that hot flashes and night sweats were linked to an 18 percent increased risk of diabetes. Another study looking at more than 3,000 women for eight years found hot flashes associated with higher insulin resistance and fasting glucose levels. Postmenopausal women also have a higher incidence of metabolic syndrome.
There are multiple theories for the interaction between metabolic health and menopausal symptoms. After menopause, women face a significant increase in central obesity, insulin resistance, and dyslipidemia, a condition marked by high cholesterol and triglycerides, all components of metabolic syndrome. There’s also the fact that estrogen decreases in menopause, which can have broad metabolic effects.
Another theory has to do with the autonomic nervous system, which regulates many things your body does involuntarily, like your heartbeat, breathing, and digestion. The autonomic nervous system also controls body temperature and glucose regulation. During a hot flash, the temperature of the skin spikes and then quickly drops as the body starts to give off heat. Researchers hypothesize that changes in the autonomic system during hot flashes are also associated with increased glucose and decreased insulin production.
Another contributing factor could be that hot flashes can disrupt sleep. Research has found that not getting enough sleep or having poor sleep quality can hinder the body’s ability to process glucose effectively.
Finally, another hypothesis suggests that hot flashes in menopause result from an energy shortage in the brain caused by less glucose crossing the blood-brain barrier, perhaps an effect of lowered estrogen levels.
What You Can Do: If the risk of metabolic syndrome rises post menopause, then maintaining healthy glucose levels before and after menopause may reduce that risk and could help lessen the severity of hot flashes around menopause.
The Metabolic Link: Many factors contribute to common skin issues like wrinkles and acne. For wrinkles, this includes thinning skin layers and a decrease of collagen and elastin, and for acne, this includes excess oil production. Research suggests excess sugar may play a role in several of these mechanisms.
The Science: Excess circulating glucose in our bloodstream can lead to a process called glycation, in which a glucose molecule bonds with proteins, fats, or DNA in a cell. These bonds form advanced glycation end products (AGEs), which can damage cells through things like inflammation and oxidative stress. We all accumulate AGEs as we age, but excess sugar (and other lifestyle factors like smoking) can accelerate the buildup.
The problem of glycation for the skin is that it alters normal collagen function. Collagen is a protein that plays a vital role in the skin’s structure and resilience. (It also helps give blood vessels their structure, which is why excess AGEs can lead to vascular conditions as well.) Glycation impairs collagen functioning in several ways. First, it leads to protein cross-linking—meaning the AGEs effectively “stick” to various structures or connect molecules that aren’t typically connected—which results in skin stiffness as collagen gets linked to the other fibers. It also changes collagen’s molecular charge, hindering the protein’s ability to interact normally with surrounding cells and proteins. Finally, enzymes in your body break down old collagen so it can generate new collagen, but in cell-line experiments, glycated collagen appears to interfere with that process. Since collagen already has a slow turnover rate, the consequences for glycated collagen can last for years.
When it comes to acne, there is a body of evidence showing correlations with elevated blood sugar.
High-glycemic diets can lead to excess insulin and a related hormone called insulin-like growth factor-1 (IGF-1), which can spur glands around hair follicles to produce oil, which ultimately contributes to acne.
In addition, a standard Western diet high in glucose and fructose (as well as dairy and meat consumption) can activate a group of proteins known as the mTOR signaling pathway, which also seems to play a role in acne through hormones and oil production.
What You Can Do: Research shows that low-glycemic diets can help with both skin aging and acne. One study found that diet changes over four months could reduce glycated collagen by 25% in people with diabetes. And a 2012 study on acne and diet found that eating low-glycemic foods (compared to high-carbohydrate foods) over ten weeks led to significantly less acne and less evidence of proteins that are known to activate oil production in the skin.
Related article: How to get healthy skin with continuous glucose monitoring (CGM)
Weight Loss and Obesity
The Metabolic Link: By the age of 45, women are more likely to be overweight or obese than men, and insulin resistance (brought on in part by excess blood glucose) plays a significant role in obesity; hormonal differences may also be a factor.
The Science: Several factors play a role in weight gain in women, including hormones that make it more difficult for women to lose weight as they age, as well as the effects of pregnancy and menopause. Blood sugar dysregulation also plays an important role.
Insulin is a crucial factor in the body’s fat storage. The hormone allows cells to take up glucose for energy. When there’s an excess of glucose in the bloodstream, increased insulin levels signal the body to store it, first in the liver as glycogen and then as fat cells around the body.
When we’re not eating, insulin levels fall, signaling to the body that it should burn stored energy, starting with excess glucose, then glycogen, and then fat. But if insulin levels remain high, the body does not signal that it should be burning through fat storage. In short, insulin prevents fat burning.
Research shows foods can affect glycemic response (the effect a meal has on blood sugar levels) in men and women differently. One study looked at how carbohydrates affected post-meal blood sugar response in men and women. It found that eating more carbs in a meal increased glucose response in both sexes. They also assessed how fat intake at a meal impacts post-meal glucose levels and found different results between men and women. In women, increasing fat in the meal led to longer-lasting high glucose values, with a slower return to pre-meal glucose levels.
The balance of sex-specific hormones plays an essential role in energy metabolism and body composition. Interestingly, while lower levels of testosterone are linked to a higher risk of diabetes in men, elevated testosterone in women, which can occur with conditions like PCOS, increases the risk. Several mechanisms may explain this difference: testosterone appears to contribute to obesity in women, but not in men, and lowering androgens in women increases insulin sensitivity, the opposite of what we see in men. In female rats, testosterone has been shown to impair glucose uptake.
Women have much more dramatic fluctuations in hormones and body mass throughout their lifetime because of reproductive factors. During menopause, for example, women lose estrogen and the protective effects that come with it. Loss of estrogen is directly linked to increased visceral fat, higher cholesterol levels, and progression of metabolic syndrome. As life expectancies have climbed in recent years, women now spend several decades with decreased estrogen, facing these health challenges from which they previously had protection with the hormone.
What You Can Do: Given the multiple potential factors in obesity for women throughout their lives, one of the best ways to maintain a healthy weight is to develop the habit of eating for stable glucose levels. This awareness of optimal dietary and lifestyle choices to keep glucose in a healthy and stable range can be especially important as metabolic challenges increase after menopause.
Metabolic Health and Dementia
The Metabolic Link: Women are more likely to suffer from dementia. While many factors may account for this, studies show people with high blood sugar have a higher risk of Alzheimer’s, dementia, and cognitive impairment.
The Science: Across the globe, the number of women with dementia is two times the number in men. According to the American Alzheimer’s Association, close to 4 million women have Alzheimer’s (a form of dementia)—almost two-thirds of all cases.
One simple potential reason: Women live longer than men, making it more likely that they will reach ages that put them at greater risk. But there are metabolic health-related reasons as well.
For example, one study found that people with prediabetes have a 1.5 times higher risk of vascular dementia, or cognitive dysfunction related to reduced blood flow to the brain. This finding held up even when the researchers controlled for confounding risk factors like BMI, smoking, and the use of certain medications.
In another study that looked at more than 80,000 people over 60 years old, researchers found metabolic syndrome increased the risk of developing Alzheimer’s disease by 11 times.
A 15-year study specific to older women and published in the journal Diabetes found high insulin resistance associated with a greater risk of cognitive dysfunction. Another study of the same demographic determined that metabolic syndrome is linked to an increased risk of cognitive impairment in older women by 66%.
The first theory linking metabolic health and dementia has to do with inflammation. In people with Alzheimer’s, a protein called beta-amyloid builds up in the brain, triggering an immune response from the body resulting in inflammation. This inflammatory response can cause neurodegeneration. Metabolic syndrome also causes inflammation, which can exacerbate Alzheimer’s disease.
Additionally, insulin receptors in the brain related to memory can be impaired by insulin resistance and consequently contribute to Alzheimer’s.
Another theory involves damage to the blood-brain barrier. Metabolic syndrome is known to contribute to oxidative stress, in which free radicals can damage cells. Oxidative stress and excess glucose and fats can contribute to vascular dysfunction and disrupt the blood-brain barrier, responsible for controlling which molecules move from the bloodstream to the brain. When that barrier is damaged, more inflammatory cells and pathogens can pass through, leading to neuroinflammation, a driver of dementia.
Finally, dysfunction of the mitochondria, or the “energy factories” of the cells in our bodies, is involved in the development of insulin resistance. Mitochondrial dysfunction is also a significant feature of Alzheimer’s disease, and this shared process likely accounts for the vital link between the conditions.
What You Can Do: Maintaining healthy glucose and insulin levels can be an essential tool for protecting the brain. In fact, the researchers from the Diabetes study conclude that their findings “suggest that a significant proportion of cases of dementia in women may be preventable by effective control of insulin homeostasis.”