Phthalate exposure may increase risk in some women

Phthalate exposure may increase risk in some women

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New research indicates that some women may be at an increased risk of diabetes due to phthalates, chemicals often used in food packaging. Image credit: Julien McRoberts/Getty Images.
  • Phthalates are chemicals widely used in food packaging, cosmetics, and children’s toys.
  • Research suggests they can interfere with hormone function, and that they are associated with obesity, allergies, and other health concerns in both children and adults.
  • Phthalates may also increase insulin resistance, raising the risk of diabetes.
  • Now, a study in women has shown that increased exposure to phthalates over a prolonged period may contribute to a higher risk of diabetes.

Plastics are everywhere, and they are extremely useful. They package our food and drink, they are in many of our clothes, and are also in our personal care products. They are even in the water we drink and the air we breathe in the form of microplastics.

While they may be useful, increasing scientific evidence is suggesting that some components of plastics may be harmful to human health.

Top of the potentially harmful list are phthalates, chemicals added to many plastics to make them flexible. Phthalates have been implicated in many health concerns, including endocrine disruption, obesity, allergies, and reproductive issues.

One hormone likely to be affected by phthalates is insulin, which controls blood glucose (sugar) levels and makes glucose available to cells. A study in adolescents found that increased urinary phthalate levels were associated with increased insulin resistance, which is often a precursor to type 2 diabetes.

Another study made similar observations in older adults, finding that exposure to one particular group of phthalates, diethylhexyl phthalates (DEHP), increased oxidative stress and insulin resistance.

Now, a longitudinal study published in The Journal of Clinical Endocrinology & Metabolism has found that women exposed to high levels of phthalates have an up to 63{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} increased risk of developing diabetes.

“The study subjects were chosen from a larger longitudinal study of midlife women to evaluate an association between phthalates in the urine and [the] development of diabetes. The study found an association between higher levels of certain phthalates and development of diabetes in white women, but not the other races studied — Black and Asian.”

Dr. Ishita Prakash Patel, board-certified endocrinologist, Texas Diabetes and Endocrinology, not involved in the study

Researchers from the University of Michigan School of Public Health studied 1,308 women from the Study of Women’s Health Across the Nation (SWAN) for 6 years.

All the women were aged between 42 and 52 years (median age 49.4 years), and not taking any exogenous reproductive hormones for the last 3 months — such as the birth-control pill or hormone replacement therapy (HRT) — when they enrolled in the study in 1996–’97.

The study looked at phthalate exposure and incident diabetes in these women in the 6 years between 1999–2000 and 2005–2006.

At the start, and in 2002–2003, all the women gave urine samples in PET (polyethylene terephthalate) tubes. PET is a plastic that does not release phthalates when stored at cool temperatures. The researchers froze the urine samples at -80 degrees Celsius until analysis in 2017–’18.

Using mass spectroscopy (HPLC-MS), the researchers measured the concentration of 12 different phthalates and phthalate metabolites in the urine samples.

The women attended nine follow-up visits during the study. Researchers classified diabetes if a woman reported using antidiabetic medications, had a doctor’s diagnosis of diabetes, and/ or had fasting blood glucose greater than 126 milligrams per deciliter (mg/dL) for two consecutive visits.

In the 6 years of the study, 61 women (4.7{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809}) developed diabetes. These women had significantly higher concentrations of all except two phthalate metabolites than women who did not develop diabetes.

“Our research is a step in the right direction towards better understanding phthalates’ effect on metabolic diseases, but further investigation is needed,” says co-author Dr. Sung Kyun Park, of the University of Michigan School of Public Health in Ann Arbor, MI.

When the researchers stratified their results by race/ethnicity, they found a positive association between phthalate metabolites and incident diabetes in white, but not Black or Asian women. The authors state that it is “unclear what might explain such racial/ethnic differences”.

Dr. Patel agreed that the reasons for this finding were unclear, telling Medical News Today that “[t]he findings could have been skewed by a selection bias — for example, missing many cases of earlier onset diabetes.”

“Another possible reason could be that products were administered differently, leading to some forms causing more harm than others,” she hypothesized.

The researchers note that those who were younger, Black, current smokers, or obese generally had higher concentrations of phthalate metabolites. They also note that of the women who developed diabetes, 89.9{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} had overweight or obesity at the start of the study.

Because it was a longitudinal study, the researchers could demonstrate that phthalate exposure occurred before diabetes diagnosis, suggesting a causative effect.

Also, the population of women in the study was diverse, with white, Black, Chinese, Japanese, and Hispanic women participating. However, the researchers noted that “given inconsistent associations across racial/ethnic groups and phthalate metabolites, a causal relationship between phthalates and diabetes remains uncertain.”

The researchers note several limitations of their study. First, phthalate concentrations in single urine samples may not reflect habitual exposure to phthalates.

Secondly, they relied on fasting glucose to diagnose diabetes. Thirdly, the follow-up time was relatively short, and the sample was relatively small. And fourthly, other environmental factors may have affected the results.

Mindful of these limitations, they call for more research into the impact of phthalates on glucose homeostasis and diabetes, saying that, “[g]iven widespread exposure to phthalates and the enormous costs of diabetes to individuals and societies, ongoing investments in the research on phthalates’ metabolic effects are warranted.”

Although this study cannot prove that phthalates cause diabetes, it does raise the possibility, and phthalates are known to have other health effects. The European Chemicals Agency states that they can “interfere with our hormonal systems and cause allergies.”

But avoiding phthalates is not always easy, as they are found in many plastics. However, some steps are being taken to reduce people’s exposure to phthalates.

Many countries have limited the use of phthalates in children’s toys and other products, as there is evidence that exposure in childhood may adversely affect normal development.

Recently, the Food and Drug Administration (FDA) limited the use of phthalates in food packaging, reducing the risk of these chemicals being absorbed into foods

And some cosmetic manufacturers are now using other ingredients in place of phthalates. People can check whether plastics contain phthalates by looking at the recycling information.

So perhaps, to be on the safe side, we should follow the advice of Dr. Patel:

“It is probably best to limit exposure to chemicals like phthalates, which can be absorbed through the skin or digestive system, as much as reasonably possible.”

Light exposure during sleep may increase diabetes risk

Light exposure during sleep may increase diabetes risk

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Light exposure during sleep may increase the risk for heart disease, diabetes, and metabolic syndrome. Gregor Prelog/EyeEm/Getty Images
  • Researchers recently investigated the health effects of light exposure during sleep.
  • They found that light exposure during even one night of sleep increases heart rate while sleeping and impairs glucose metabolism the following morning.
  • They say that sleeping without exposure to light is likely beneficial for cardiometabolic health.

Exposure to artificial light at night is widespread globally and is linked to negative effects on health and well-being.

Researchers from Northwestern University in Chicago recently investigated the biological effects of different light exposure levels while sleeping.

They found that exposure to moderate ambient light during one night of sleep can impair glucose and cardiovascular regulation and increase risk factors for heart disease, diabetes, and metabolic syndrome.

The study appears in PNAS.

Another study, published in 2019, found that artificial light at night (ALAN), such as from a nightlight or television, is linked to obesity in women. These findings suggest that light exposure during sleep may negatively affect metabolic regulation.

Other research indicates that blue-enriched light exposure in the morning and evening alters glucose metabolism and increases insulin resistance compared with dim light exposure.

Another study found that higher levels of ALAN are linked to higher rates of type 2 diabetes among older adults.

The mechanisms underlying ALAN’s impact on metabolic functioning are poorly understood.

The scientists recruited 20 young adults for a 3-day and 2-night laboratory stay. A week before the study, they measured participants’ sleep habits using actigraphy and sleep diaries.

The participants were then randomized to partake in one of two sleeping conditions:

  • The room light condition: Participants slept with a dim light of less than 3 lux (lx) on the first night and an overhead room light at 100 lx on the second night.
  • The dim light condition: Sleeping with a dim light of less than 3 lx on both nights

On Days 1 and 2 of the experiment, the participants provided blood samples before and after food intake to assess melatonin and blood glucose levels. They also underwent overnight polysomnography (PSG) to assess their sleep quality.

The participants also filled in surveys every 2 hours that they were awake to evaluate their subjective sleepiness, hunger, and mood changes.

Meanwhile, nurses collected blood pressure readings every hour, alongside heart rate readings every 4 hours.

The researchers found that exposure to a single night of 100 lx room lighting increased heart rate during sleep and insulin resistance the following morning.

Compared with the dim light condition, participants exposed to 100 lx lighting during sleep had more N2 sleep — one of the deeper stages of sleep — and less slow-wave sleep — which is important for memory consolidation. They also had less REM sleep — the dreaming phase of sleep.

The researchers noted no changes among PSG-derived measures of cortical arousal, sleep fragmentation, or wake-sleep stage stability and no difference in melatonin levels between the two groups. They say this might be because only 5-9{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of light is transmitted through closed eyelids.

When asked what may explain the link between ALAN and the observed effects on heart rate and glucose metabolism, Phyllis C Zee, MD., Ph.D., the correspondent author of the study, told Medical News Today:

“There are potentially three possibilities. [The first is that light] can cause awakening or arousal. We found small changes [in these measures, but they did not] correlate with an increase in insulin resistance. So this is unlikely to be a primary mechanism.”

“Secondly, light can affect the circadian clock and affect melatonin secretion. However, we found no significant difference in melatonin levels,” Dr. Zee added.

“[We thus hypothesize] that light activates brain regions that regulate the autonomic nervous system because there was a relationship between the changes in heart variability and insulin resistance,” she explained.

Dale Sandler, Ph.D., is a senior investigator and chief of the Epidemiology Branch of the National Institute of Environmental Health Services (NIEHS), who was not involved in the study. Dr. Sandler agreed with Dr. Zee but added that “subtle shifts in sleep stages could [also] play a role.”

The researchers concluded that avoiding ALAN may benefit cardiometabolic health.

When asked what limitations there may be to this research, Yong-Moon (“Mark”) Park MD, MS, Ph.D., assistant professor at the University of Arkansas, who was not involved in the study, toldMNT:

“The findings came from a study of 20 healthy young adults. So the results might not apply to people with different age groups and people with comorbidities. [Also], the effect of ALAN on cardiometabolic health may differ by sex and race/ethnicity, which was not addressed in this study.”

“As the authors mentioned, the effects of altering light intensities, duration, and wavelengths on cardiometabolic health were not assessed in this study. The [link between blue light and cardiometabolic dysfunction] may be important to look at in the future as the use of smartphones, tablets, and laptops have increased dramatically in the bedroom at night,” he added.

“The experiment only involved one night of sleep in room light for the exposed group,” added Dr. Sandler, “Obesity and diabetes do not develop overnight. What may be most important is long-term exposures, and it is possible that some effects that were not observed after one night could develop over constant longer-term exposure.”

“There are many things that contribute to risk for obesity, diabetes, and cardiometabolic dysfunction. Many of these factors are difficult for individuals to control. But turning off the lights at bedtime may be a simple thing that people can do to lessen the chances of developing these conditions.”

– Dr. Sandler

Exposure to air pollutants may amplify risk for depression

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A new study looks at the impact of pollution on depression risk in people with a genetic susceptibility. Jelena Jojic Tomic/Stocksy
  • Exposure to air pollution is associated with cognitive deficits and an increased risk of depression.
  • A recent study examined how air pollutants impact brain networks to mediate changes in cognitive function and enhance the risk of depression.
  • The results suggest that genetic susceptibility to depression combined with high levels of exposure to air pollution have a disproportional effect on brain networks involved in cognition and stress.
  • Exposure to air pollutants was associated with activation of brain networks expressing depression-associated genes, suggesting that exposure to air pollution may cause adverse mental health effects by acting on the same brain networks related to genetic mechanisms of depression.
  • This suggests that individuals with a genetic susceptibility to depression may be more vulnerable to the adverse effects of air pollution on mental health.

Besides having a detrimental effect on physical health, prolonged exposure to air pollutants is also associated with adverse mental health effects.

Exposure to air pollutants, including fine particulate matter, may be associated with impaired cognitive functioning and depression.

Fine particulate matter, also known as PM2.5, consists of tiny inhalable particles smaller than 2.5 microns. These particles commonly come from industrial sources and vehicles.

How exposure to PM2.5 might increase the risk of depression is not well understood.

Also, scientists do not know whether air pollution can interact with a genetic predisposition for depression to increase the likelihood of depression.

Individuals with a genetic predisposition for a particular disease may have an increased likelihood of developing the condition in the presence of certain environmental factors or due to behaviors such as smoking.

A recent study investigated the effects of PM2.5 exposure, in combination with a genetic predisposition for depression, on brain networks involved in cognition and social stress.

The study’s lead author, Dr. Hao Yang Tan, a scientist at the Lieber Institute in Baltimore, MD, told Medical News Today:

“The study reveals for the first time how air pollution and genes interact with one another to impact important cognitive and emotional circuitry of the brain. Air pollution is changing the expression of genes that are conducive to depression.”

“Previous studies have observed air pollution’s link to depression, but our results are the first to show a direct, neurological cause,” he explained.

“What is most intriguing is that the two factors are linked in such a way that they have a multiplier effect on one’s risk of depression. That is, together, risk genes and bad air raise the risk of depression much more than either factor does in isolation.”

The study appears in the journal Proceedings of the National Academy of Sciences.

The study recruited 352 healthy participants residing in Beijing, China. Beijing has relatively high levels of air pollution, including high concentrations of PM2.5.

For each participant, the researchers studied several specific genetic variants that are associated with depression. From this information, they estimated their genetic susceptibility to depression.

To estimate the PM2.5 exposure levels for each individual, the researchers used air monitoring data obtained from the city air quality monitoring station closest to each person’s home for 6 months before the study.

Depression is associated with cognitive deficits and higher levels of anxiety-depression. In other words, these individuals have an increased tendency to react anxiously or with depressive symptoms to a situation. The scientists evaluated each participant’s levels of anxiety-depression using a questionnaire.

The researchers first examined the effects of PM2.5 exposure on cognition and characteristics associated with depression.

They found that PM2.5 exposure was associated with poor performance on cognitive tests involving reasoning and problem-solving. Higher anxiety-depression was also associated with PM2.5 exposure.

Next, the researchers examined brain networks involved in cognition and processing stress-related information and their association with PM2.5 exposure and genetic risk for depression.

The researchers measured the participants’ brain activity while conducting a simple cognitive task using functional magnetic resonance imaging.

To evaluate the influence of social stress on brain activity during the cognitive task, researchers showed the participants the image of a competitor and compared their performance with that of the competitor.

Higher levels of PM2.5 exposure were associated with slower reaction times during the cognitive task, and this effect of PM2.5 exposure became amplified during social stress.

Social stress had a more pronounced effect on brain networks in individuals with a genetic predisposition for depression and greater PM2.5 exposure.

The effect of social stress on brain networks due to the combination of genetic risk and air pollution was greater than the sum of the effects produced by each factor alone. These results suggest that air pollution may interact with genetic risk for depression to influence brain networks.

The dorsolateral prefrontal cortex is a brain region involved in several processes, including cognition. It was one of the key regions whose connectivity changed during the cognitive task in individuals with higher PM2.5 exposure and a genetic predisposition for depression.

Significantly, scientists have observed changes in the dorsolateral prefrontal cortex activity of healthy individuals with a genetic predisposition for depression and individuals with depression.

To further examine the interaction between genetic risk for depression and air pollution, the researchers investigated whether the combination of these factors differentially influenced brain networks involved in depression.

The researchers mapped the brain networks involved in depression by identifying brain regions expressing high levels of depression-associated genes.

The researchers used the online database Allen Brain Atlas, which provides detailed gene expression data for brain regions. They then identified brain regions that showed correlated expression of genes associated with depression.

The researchers examined if this pattern of coexpression of depression-associated genes in brain regions obtained using the atlas was similar to the brain connectivity patterns of the participants during the cognitive tests.

The pattern of coexpression of depression-associated genes derived using the atlas predicted brain connectivity patterns observed during the cognitive task. However, this was only the case for those with greater exposure to PM2.5 levels and a higher genetic predisposition for depression.

The correlation was weaker in individuals with a lower genetic risk of depression or lower exposure to PM2.5.

This suggests that exposure to PM2.5 air pollutants affects brain network functions associated with the genetic mechanisms of depression.

The researchers also conducted similar analyses focused on the association between the connectivity patterns of the dorsolateral prefrontal cortex with other brain regions and the coexpression of depression-associated genes in these regions.

The co-expression of depression-associated genes tracked the connectivity patterns to and from the dorsolateral prefrontal cortex in individuals with a genetic risk for depression, higher PM2.5 exposure levels, or both.

Interestingly, the co-expressed genes that correlated with brain connectivity patterns of the prefrontal cortex included some involved in neuroinflammation.

Depression is associated with chronic, low-grade inflammation, further suggesting that PM2.5 exposure may interact with depression-associated genes to increase the risk of depression.

“This is possibly the first study to directly implicate how genes for brain disorders operate in concert with each other and affect important cognitive and emotional functions in the live functioning brain, and the impact of air pollution and genes in multiplying the effects of each on these brain functions,” Dr. Tan told MNT.

“It is now [in] much less doubt that there are direct impacts of air pollution on how genes operate in the brain to affect risk for these neuropsychiatric disorders,” he added.

Dr. Tan noted: “Individuals can limit their outdoor activities when pollution is high and be mindful of their risk. Our study would strongly suggest that individuals with genetic risk, e.g., [a] family history of brain disorders, may need to be more careful, and minimize [as much as] possible their exposures to any air pollution.”

“Armed with this knowledge, leaders and public health officials around the globe have ample evidence that additional air pollution controls will lead to lower rates of depression — particularly in densely populated urban areas where air pollution is highest, and stress from socioeconomic and other inequities are greater.”

– Dr. Tan

Dr. Perry Sheffield, an environmental health researcher at Icahn School of Medicine at Mount Sinai, New York, noted that this study “helps drive home the point that when we talk about vulnerable groups — and here I mean groups of people who are more likely to experience negative health effects from a certain environmental exposure — we are ultimately talking about all of us. Each of us is vulnerable probably in multiple ways, and our specific vulnerabilities change during our lives.”

“Vulnerability can certainly be socially and unjustly determined — as we see driving racial and ethnic health disparities — but it can [also be] influenced by underlying genetics, as we see here in relation to air pollution and depression, and certainly by life stage or age,” she continued.

“The value of illustrating these associations in a study like this is that it helps tell the story of why clean air, water, and the overall environment matter for the health of people and communities.”

– Dr. Sheffield

Dr. Tan explained to MNT, “An important strength is that we have studied the brain impacts of air pollution using arguably the most direct measurements of live human brain function, which is MRI technologies.”

“We have studied a large sample of individuals. We have also eliminated many other factors that could have interfered with the study.” For instance, their sample was “socioeconomically homogeneous.”

“We have additionally examined patterns of how risk genes for depression operated in concert with each other in postmortem human brains and found that these patterns corresponded well with how the live human brain operated, and especially so in individuals with genetic risk for depression and exposed to high air pollution.”

Dr. Tan acknowledged that there were a few limitations to their approach, saying the team “studied only a limited set of genes for depression, and that’s likely only the tip of the iceberg.”

“There are likely many other genes [for] neuropsychiatric disorders implicated in the brain impacts of air pollution. Understanding these more comprehensively would enable us to better identify people at risk, and perhaps identify various pharmacological or other ways to protect the vulnerable,” he concluded.