Tag: sex differences

Categories : COVID GeneticsTags :

Key Gene may Protect Against Severe COVID Infections in Men Under 75

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A certain variant of a key anti-inflammatory gene protects men under age 75 from severe illness and death when hospitalised from COVID, a genetic analysis of their blood shows. According to the authors of a major study published in The Journal of Infectious Diseases, the protective gene in question, an interleukin-1 receptor antagonist (IL1RN) variant, appears to tamp down inflammation, which can get out of control in severe cases SARS-CoV-2 infection.

The study showed that 124 men between the ages of 19 and 74 who possessed the IL1RN variant, called rs419598, were less likely to become severely ill after hospitalisation for COVID, and 80% less likely to die from the disease.

IL1RN is expressed naturally in the body. Different types of interleukin genes are known to dial inflammation up or down in the context of arthritis, and researchers say the results of the current study suggest that a similar dynamic influences the interleukin-1-related inflammation seen in COVID patients.

The findings, from researchers at NYU Grossman School of Medicine, stand out because historically more men than women are known to die from COVID, and the IL1RN rs419598 variant appears to selectively protect only men up to age 74, but not beyond that as age-related chronic illnesses unfold.

The research team used sequencing technologies for the study to determine the presence of specific genes or variations in the letter code that makes up genes in blood samples from 2589 men and women hospitalised for COVID at NYU Langone’s Tisch Hospital in Manhattan from March 2020 to March 2021.

More than half of the men and women in the study were older than age 60 and obese, factors that are known to increase the risk of death from the viral infection. Overall, more men than women (240 men, at 60.5%; and 157 women, at 39.5%) died from their disease, with women 20% less likely to die than men.

“Our study results show that among hospitalised patients, while women are still overall less likely than men to die from COVID-19, those men age 74 and younger who possess the IL1RN gene variant rs419598 are much less likely to suffer the severe inflammation tied to SARS-CoV-2 infection and less likely to die from the disease,” said study colead investigator and molecular biologist Mukundan Attur, PhD. Attur is an associate professor in the Department of Medicine at NYU Langone Health.

Among the study’s other findings was that average blood levels of the anti-inflammatory protein IL-1Ra, coded by IL1RN, were 14 times higher in 181 hospitalised men than in healthy male study controls from the general population, and 10 times as high in 178 hospitalised women than in healthy females. The increased levels of IL-1Ra in women did not result in any statistically significant mortality reductions.

“Our analysis offers substantial evidence of the biological link between the severe inflammation seen in SARS-CoV-2 and that which occurs in rheumatoid arthritis,” said study senior investigator Steven Abramson, MD, the Frederick H. King Professor of Internal Medicine at NYU Langone.

Abramson, a rheumatologist who also serves as chair of the Department of Medicine and chief academic officer at NYU Langone, says previous research has shown that such rheumatoid inflammation is lower in people who possessed one of the three IL1RN variants analysed in the study.

More importantly, Abramson says, the new research suggests that restraining the interleukin-1 biological pathway, which is in part tamped down by the anti-inflammatory protein IL-1Ra, could help prevent the severe inflammation seen in SARS-CoV-2 infection. Further research, he says, is warranted into whether IL-1-inhibiting therapies, such as the IL1 receptor antagonists anakinra, canakinumab, and rilonacept, are effective against Covid infection.

Abramson already has plans to investigate if the IL-1 pathway plays a role in long Covid, when people experience new or lingering symptoms, such as fatigue and ‘brain fog’, months after recuperating from their initial infection.

Abramson points out that the new study adds to the growing scientific evidence about the biological factors that contribute to gender differences seen in deaths from COVID, which are known to vary widely across the United States.

Source: NYU Langone Health / NYU Grossman School of Medicine

Categories : Cardiovascular DiseaseTags :

New Advance against Heart Failure Caused by Y Chromosome Loss

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Chromosomes. Credit: NIH

Researchers have discovered a gene on the Y chromosome that contributes to the greater incidence of heart failure in men when the Y chromosome is lost to ageing.

Y chromosome loss in men occurs progressively throughout life and can be detected in approximately 40% of 70-year-old men. In 2022, Kenneth Walsh, PhD, at University of Virginia discovered that this loss can contribute to heart muscle scarring and lead to heart failure. (That finding was the first to directly link Y chromosome loss to a specific harm to men’s health; Y chromosome loss is increasingly thought to play a role in diseases ranging from Alzheimer’s to cancer.)

In an important follow-up finding published in Nature Cardiovascular Research, Walsh and his team have discovered how Y chromosome loss triggers changes in heart immune cells that make the cells more likely to cause scarring and heart failure.

Further, the researchers found they could reverse the harmful heart changes by giving lab mice a drug that targets the process of fibrosis that leads to the heart scarring, which could lead to a similar treatment for men.

“Our previous work identified that it was loss of the entire Y chromosome that contributed to heart disease in men,” said Walsh, the director of UVA’s Hematovascular Biology Center. “This new work identified a single gene on the Y chromosome that can account for the disease-promoting effects of Y chromosome loss.”

About Y chromosome loss

Unlike women, who have two X chromosomes, men have an X and a Y. For a long time, the genes found on the Y chromosome were not thought to play important roles in disease. Sex hormones, scientists thought, explained the differences in certain diseases in men and women. But Walsh’s groundbreaking work has helped change that perception. It also suggested an explanation for why heart failure is more common in men than women. (Cardiovascular disease, which includes heart failure, is the leading cause of death worldwide.)

Y chromosome loss occurs in only a small percentage of affected men’s cells. This results in what is called “mosaicism,” where genetically different cells occur within one individual. Researchers aren’t entirely sure why this partial Y chromosome loss occurs, but predominantly it strikes elderly men and men who smoke compared to those who don’t.

To better understand the effects of Y chromosome loss, Walsh and his team examined genes found on the Y chromosome to determine which might be important to heart scarring. One gene they looked at, Uty, helps control the operating instructions for immune cells called macrophages and monocytes, the scientists determined. When the Uty gene was disrupted, either individually or through Y chromosome loss, that triggered changes in the immune cells in lab mice. Suddenly, the macrophages were much more “pro-fibrotic,” or prone to scarring. This accelerated heart failure as well, the scientists found.

“The identification of a single gene on the Y chromosome provides information about a new druggable target to treat fibrotic diseases,” said Walsh, of UVA’s Division of Cardiovascular Medicine and Robert M. Berne Cardiovascular Research Center.

Walsh and his team were able to prevent the harmful changes in the mice’s macrophages by giving them a specially designed monoclonal antibody. This halted the harmful changes in the heart, suggesting the approach might, with further research, lead to a way to treat or avoid heart failure and other fibrotic diseases in men with Y chromosome loss.

“Currently, we are working with our clinician colleagues in the Division of Cardiovascular Medicine at UVA to assess whether loss of the Y chromosome in men is associated with greater scarring in the heart,” Walsh said. “This research will provide new avenues for understanding the causes of heart disease.”

Based on their findings, Walsh and his team believe that a small group of genes found on the Y chromosome may have big effects on a wide array of diseases. Their new work identifies mechanisms that may lead to this, and they are hopeful that further research will provide a much better understanding of unknown causes of sickness and death in men.

“This research further documents the utility of studying the genetics of mutations that are acquired after conception and accumulate throughout life,” Walsh said. “These mutations appear to be as important to health and lifespan as the mutations that are inherited from one’s parents. The study of these age-acquired mutations represents a new field of human genetics.”

Source: University of Virginia Health System

Categories : Cardiovascular DiseaseTags :

Getting too Little Sleep Linked to High Blood Pressure

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Sleeping fewer than seven hours is associated with a higher risk of developing hypertension over time, according to a study presented at the American College of Cardiology’s Annual Scientific Session.

While the association between sleep patterns and hypertension has been reported, evidence about the nature of this relationship has been inconsistent, according to researchers. The current analysis pools data from 16 studies conducted between January 2000 and May 2023, evaluating hypertension incidence in 1 044 035 people from six countries without a prior history of hypertension over a median follow-up of five years (follow-up ranged from 2.4 to 18 years). Short sleep duration was significantly associated with a higher risk of developing hypertension after adjusting for demographic and cardiovascular risk factors, including age, sex, education, BMI, blood pressure, smoking status etc. Furthermore, the association was found to be even stronger for those getting less than five hours of sleep.

“Based on the most updated data, the less you sleep – that is less than seven hours a day – the more likely you will develop high blood pressure in the future,” said Kaveh Hosseini, MD, assistant professor of cardiology at the Tehran Heart Center in Iran and principal investigator of the study. “We saw a trend between longer sleep durations and a greater occurrence of high blood pressure, but it was not statistically significant. Getting seven to eight hours of sleep, as is recommended by sleep experts, may be the best for your heart too.”

The study found that sleeping less than seven hours was associated with a 7% increased risk of developing hypertension, which spiked to 11% when reported sleep duration was less than five hours. By comparison, diabetes and smoking are known to heighten one’s risk of hypertension by at least 20%, Hosseini said.

While the study did not look at why this might be the case, Hosseini said that disrupted sleep could be to blame. For example, he said lifestyle habits or comorbid conditions such as overeating, alcohol use, nightshift work, certain medication use, anxiety, depression, sleep apnoea or other sleep disorders may be factors.

Researchers were surprised there were no age-based differences in the association between sleep duration and hypertension given that sleep patterns tend to shift with age. Participants ranged in age from 35.4 years to 60.9 years and 61% were female. When compared with men, females who reported less than seven hours of sleep had a 7% greater risk of developing hypertension.

“Getting too little sleep appears to be riskier in females,” Hosseini said. “The difference is statistically significant, though we are not sure it’s clinically significant and should be further studied. What we do see is that lack of good sleep patterns may increase the risk of high blood pressure, which we know can set the stage for heart disease and stroke.”

It’s important for people to talk with their health care team about their sleep patterns, especially if they have disrupted sleep that might be due to obstructive sleep apnoea. Sleep apnoea has been tied to higher rates of high blood pressure, stroke and coronary artery disease.

This study has several limitations, including that sleep duration was based on self-reported questionnaires, so changes in sleep duration over the follow-up period were not assessed. Moreover, there were variations in how short sleep duration was defined between the studies (fewer than five or six hours).

“Further research is required to evaluate the association between sleep duration and high blood pressure using more accurate methods like polysomnography, a method for evaluating sleep quality more precisely,” Hosseini said. “Moreover, the variations in reference sleep duration underline the need for standardised definition in sleep research to enhance the comparability and generalisability of findings across diverse studies.”

Source: American College of Cardiology

Categories : GenderTags :

Fear may Make Women and Men Take Different Risk-based Decisions

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Women experiencing fear tended to prioritise smaller short-term gain compared to men

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Fear may affect women’s decisions in choosing immediate rewards versus larger delayed ones, while men’s decisions appear unaffected by emotion, according to a study published March 20, 2024 in the open-access journal PLOS ONE by Eleonora Fiorenzato, Patrizia Bisiacchi, and Giorgia Cona from the University of Padua, Italy.

Decision making is complex and still not fully understood, especially when weighing short- versus long-term benefits or costs. The known phenomenon “delay discounting” describes the common tendency to prefer an immediate reward rather than a later one, even if the later reward is significantly greater. In this study, Fiorenzato and colleagues examined how emotions like fear and joy, along with gender, affect decision making, especially when weighing immediate versus later rewards.

The authors recruited 308 participants (63% women, 37% men) via a social media survey. Survey participants were shown a brief standardised and validated movie clip intended to induce an emotional state – for the fear group, this was a scary movie, like The Sixth Sense or Silence of the Lambs; for the joy group, this was a positive documentary clip with subjects like forests or waterfalls; the neutral affect group watched a documentary clip on urban environments. Then, the subjects were asked hypothetical reward questions such as: “Would you rather have €20 000 today or €40 000 after 3 years?”

Women in the fear group were significantly more likely to use “delay discounting” when choosing financial rewards (selecting the immediate, smaller amount) compared to men in the fear group or women in the joy or neutral movie groups. There were no significant gender differences for decisions made across the joy or neutral movie groups, and men’s decision-making on monetary rewards appeared to be unaffected by their emotional state. The findings suggest that fear specifically might provoke different types of time-bound decision making for women versus men – the authors speculate these may be due to either differences in evolutionary strategies around safety versus risk, or different emotion-regulation approaches in stressful situations.

The authors note that the sample size and range of emotions studied here is relatively small compared to the real world. However, the suggestion that emotions (particularly negative ones such as fear) and gender do interact with regard to intertemporal choices warrants further investigation.

The authors add: “Women are more prone to choose immediate rewards when in a fearful emotional state than when in joyful one. Our research underscores the importance of gender as an influential factor in the interaction between emotions and decision-making processes.”

Categories : AntibioticsTags :

Age and Sex Associated with Patient’s Likelihood of Antimicrobial Resistance

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A person’s age, sex and location are correlated with the chance that they have a bloodstream infection that is resistant to antibiotics, according to a new study published March 14th in PLOS Medicine by Gwenan Knight of the London School of Hygiene and Tropical Medicine, UK, and colleagues.

Antimicrobial resistance (AMR), in which infections cannot be treated with antibiotics, is a major global public health threat.

Little has been known about how the prevalence of resistance varies with age and sex even though antibiotic usage, changes in immune function, and exposure to high-risk settings are all linked to age and sex.

In the new study, researchers analyzed data collected as part of routine surveillance between 2015 and 2019 on bloodstream infections in 944,520 individuals across 29 European countries.

The team looked at which bacterial species were isolated and sent to the surveillance service, and which antibiotics were used to treat the infections.

Distinct patterns in resistance prevalence by age were observed throughout Europe but varied across bacterial species.

For most but not all bacteria, peaks in resistance were seen at the youngest and oldest ages.

The occurrence of methicillin-resistant Staphylococcus aureus (MRSA) increased with age and the occurrence of aminopenicillin resistance in Escherichia coli decreased with age.

Some antimicrobial resistance profiles peaked in middle-age; Pseudomonas aeruginosa was most likely to be resistant to several antibiotics around 30 years of age and, for women, the incidence of bloodstream infections due to E. coli peaked between ages 15 and 40. There were other important differences between sexes; in general, men had a higher risk of antimicrobial resistance than women.

“These findings highlight important gaps in our knowledge of the epidemiology of antimicrobial resistance that are difficult to explain through known patterns of antibiotic exposure and healthcare contact,” the authors say.

“Our findings suggest that there may be value in considering interventions to reduce antimicrobial resistance burden that take into account important variations in antimicrobial resistance prevalence with age and sex.”

The authors add, “Our findings, that the prevalence of resistance in bloodstream infections across Europe varies substantially by age and sex, highlights important gaps in our knowledge of the spread and selection of AMR. In order for us to address this growing threat to public health, we now need data from a wider range of sources to determine the contribution that cultural versus natural history differences have in driving these patterns globally and the role that they play in the increasing rates of AMR being seen.”

Categories : Ageing ExerciseTags :

Yoga Provides Unique Cognitive Benefits to Older Women at Risk of Alzheimer’s disease

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A new UCLA Health study found Kundalini yoga provided several benefits to cognition and memory for older women at risk of developing Alzheimer’s disease including restoring neural pathways, preventing brain matter decline and reversing aging and inflammation-associated biomarkers – improvements not seen in a group who received standard memory training exercises.

The findings, published in the journal Translational Psychiatry, are the latest in a series of studies led by UCLA Health researchers over the past 15 years into the comparative effects of yoga and traditional memory enhancement training on slowing cognitive decline and addressing other risk factors of dementia.

Led by UCLA Health psychiatrist Dr. Helen Lavretsky of the Jane and Terry Semel Institute for Neuroscience and Human Behavior, this latest study sought to determine whether Kundalini yoga could be used early on to prevent cognitive decline and trajectories of Alzheimer’s disease among postmenopausal women.

Women have about twice the risk of developing Alzheimer’s disease compared to men due to several factors including longer life expectancy, changes in oestrogen levels during menopause and genetics.

In the new study, a group of more than 60 women ages 50 and older who had self-reported memory issues and cerebrovascular risk factors were recruited from a UCLA cardiology clinic. The women were divided evenly into two groups. The first group participated in weekly Kundalini yoga sessions for 12 weeks while the other one group underwent weekly memory enhancement training during the same time period. Participants were also provided daily homework assignments.

Kundalini yoga is a method that focuses on meditation and breath work more so than physical poses. Memory enhancement training developed by the UCLA Longevity centre includes a variety of exercises, such as using stories to remember items on a list or organising items on a grocery list, to help preserve or improve long-term memory of patients.

Researchers assessed the women’s cognition, subjective memory, depression and anxiety after the first 12 weeks and again 12 weeks later to determine how stable any improvements were. Blood samples were also taken to test for gene expression of aging markers and for molecules associated with inflammation, which are contributing factors to Alzheimer’s disease. A handful of patients were also assessed with MRIs to study changes in brain matter.

Researchers found the Kundalini yoga group participants saw several improvements not experienced by the memory enhancement training group. These included significant improvement in subjective memory complaints, prevention in brain matter declines, increased connectivity in the hippocampus which manages stress-related memories, and improvement in the peripheral cytokines and gene expression of anti-inflammatory and anti-aging molecules.

“That is what yoga is good for – to reduce stress, to improve brain health, subjective memory performance and reduce inflammation and improve neuroplasticity,” Lavretsky said.

Among the memory enhancement training group, the main improvements were found to be in the participants’ long-term memory.

Neither group saw changes in anxiety, depression, stress or resilience, though Lavretsky stated this is likely because the participants were relatively healthy and were not depressed.

While the long-term effects of Kundalini yoga on preventing or delaying Alzheimer’s disease require further study, Lavretsky said the study demonstrates that using yoga and memory training in tandem could provide more comprehensive benefits to the cognition of older women.

“Ideally, people should do both because they do train different parts of the brain and have different overall health effects,” Lavretsky said. “Yoga has this anti-inflammatory, stress-reducing, anti-aging neuroplastic brain effect which would be complementary to memory training.”

Source: University of California – Los Angeles Health Sciences

Categories : Exercise GenderTags :

Women Get the Same Exercise Benefits as Men, but with Less Effort

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A new study from the Smidt Heart Institute at Cedars-Sinai shows there is a gender gap between women and men when it comes to exercise. The findings, published in the Journal of the American College of Cardiology (JACC), show that women can exercise less often than men, yet receive greater cardiovascular gains.

“Women have historically and statistically lagged behind men in engaging in meaningful exercise,” said Martha Gulati, MD, director of Preventive Cardiology in the Department of Cardiology in the Smidt Heart Institute at Cedars-Sinai, the Anita Dann Friedman Chair in Women’s Cardiovascular Medicine and Research and co-lead author of the study.

“The beauty of this study is learning that women can get more out of each minute of moderate to vigorous activity than men do. It’s an incentivising notion that we hope women will take to heart.”

Investigators analysed data from 412 413 US adults utilising the National Health Interview Survey database. Participants between the time frame of 1997 to 2019 – 55% of whom were female – provided survey data on leisure-time physical activity.

Investigators examined gender-specific outcomes in relation to frequency, duration, intensity and type of physical activity.

“For all adults engaging in any regular physical activity, compared to being inactive, mortality risk was expectedly lower,” said Susan Cheng, MD, MPH, the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science, director of the Institute for Research on Healthy Aging in the Department of Cardiology in the Smidt Heart Institute, and senior author of the study.

“Intriguingly, though, mortality risk was reduced by 24% in women and 15% in men.”

The research team then studied moderate to vigorous aerobic physical activity, such as brisk walking or cycling, and found that men reached their maximal survival benefit from doing this level of exercise for about five hours per week, whereas women achieved the same degree of survival benefit from exercising just under about 2 ½ hours per week.

Similarly, when it came to muscle-strengthening activity, such as weightlifting or core body exercises, men reached their peak benefit from doing three sessions per week and women gained the same amount of benefit from about one session per week.

Cheng said that women had even greater gains if they engaged in more than 2 ½ hours per week of moderate to vigorous aerobic activity, or in two or more sessions per week of muscle-strengthening activities.

The investigators note their findings help to translate a longstanding recognition of sex-specific physiology seen in the exercise lab to a now-expanded view of sex differences in exercise-related clinical outcomes.

With all types of exercise and variables accounted for, Gulati says there’s power in recommendations based on the study’s findings.

“Men get a maximal survival benefit when performing 300 minutes of moderate to vigorous activity per week, whereas women get the same benefit from 140 minutes per week,” Gulati said.

“Nonetheless, women continue to get further benefit for up to 300 minutes a week.”

Christine M. Albert, MD, MPH, chair of the Department of Cardiology in the Smidt Heart Institute and the Lee and Harold Kapelovitz Distinguished Chair in Cardiology, says concrete, novel studies like this don’t happen often.

“I am hopeful that this pioneering research will motivate women who are not currently engaged in regular physical activity to understand that they are in a position to gain tremendous benefit for each increment of regular exercise they are able to invest in their longer-term health,” said Albert, professor of Cardiology.

Source: Cedars-Sinai Medical Center

Categories : Ageing GenderTags :

COVID, Opioid Pandemic Widen Gender Gap in Life Expectancy in the US

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Women have long been known to outlive men. But new research published in JAMA Internal Medicine shows that, at least in the United States, the gap has been widening for more than a decade. Among the factors driving the trend are the COVID pandemic and the opioid overdose epidemic.

The study, led by UC San Francisco and Harvard T.H. Chan School of Public Health, found the difference between how long American men and women live increased to 5.8 years in 2021, the largest since 1996. This is an increase from 4.8 years in 2010, when the gap was at its smallest in recent history.

The pandemic, which took a disproportionate toll on men, was the biggest contributor to the widening gap from 2019–2021, followed by unintentional injuries and poisonings (mostly drug overdoses), accidents and suicide.

“There’s been a lot of research into the decline in life expectancy in recent years, but no one has systematically analysed why the gap between men and women has been widening since 2010,” said the paper’s first author, Brandon Yan, MD, MPH, a UCSF internal medicine resident physician and research collaborator at Harvard Chan School.

Life expectancy in the US dropped in 2021 to 76.1 years, falling from 78.8 years in 2019 and 77 years in 2020.

The shortening lifespan of Americans has been attributed in part to so-called “deaths of despair.” The term refers to the increase in deaths from such causes as suicide, drug use disorders and alcoholic liver disease, which are often connected with economic hardship, depression and stress.

“While rates of death from drug overdose and homicide have climbed for both men and women, it is clear that men constitute an increasingly disproportionate share of these deaths,” Yan said.

Interventions to reverse a deadly trend

Using data from the National Center for Health Statistics, Yan and fellow researchers from around the country identified the causes of death that were lowering life expectancy the most. Then they estimated the effects on men and women to see how much different causes were contributing to the gap.

Prior to the COVID pandemic, the largest contributors were unintentional injuries, diabetes, suicide, homicide and heart disease.

But during the pandemic, men were more likely to die of the virus. That was likely due to a number of reasons, including differences in health behaviours, as well as social factors, such as the risk of exposure at work, reluctance to seek medical care, incarceration and housing instability. Chronic metabolic disorders, mental illness and gun violence also contributed.

Yan said the results raise questions about whether more specialised care for men, such as in mental health, should be developed to address the growing disparity in life expectancy.

“We have brought insights to a worrisome trend,” Yan said. “Future research ought to help focus public health interventions towards helping reverse this decline in life expectancy.”

Yan and co-authors, including senior author Howard Koh, MD, MPH, professor of the practice of public health leadership at Harvard Chan School, also noted that further analysis is needed to see if these trends change after 2021.

“We need to track these trends closely as the pandemic recedes,” Koh said. “And we must make significant investments in prevention and care to ensure that this widening disparity, among many others, do not become entrenched.”

Source: University of California – San Francisco

Categories : Gender Injury & TraumaTags :

Females Less Able to Recover from ACL Injuries

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Injuries of the knee’s anterior cruciate ligament (ACL) are typically thought to be caused by acute traumatic events, such as sudden twists. Published in the Journal of Orthopaedic Research, new work analysing an animal model of ACLs suggests that such injuries can also occur as a result of chronic overuse, specifically due to a reduced ability to repair microtraumas associated with overuse. Importantly, the team said, females also are less able to heal from these microtraumas than males, which may explain why females are two to eight times more likely to tear their ACL ligaments than males.

“ACL tears are one of the most common injuries, affecting more than 200 000 people in the US each year, and women are known to be particularly susceptible,” said principal investigator Spencer Szczesny, associate professor of biomedical engineering and of orthopaedics and rehabilitation at Penn State. “While recent research suggests that chronic overuse can lead to ACL injuries, until now, no one had investigated the differential biological response of female and male ACLs to applied force.”

In the Penn State-led study, researchers placed ACLs from deceased male and female rabbits in a custom-made bioreactor that simulated the conditions of a living animal but allowed direct observation and measurement of the tissue. Next, they applied repetitive forces to the ACLs that mimicked those that would naturally occur during activities such as standing, walking and trotting and measured the expression of genes related to healing.

In male samples, the team found that low and moderate applied forces, such as those that would occur during standing or walking, resulted in increased expression of anabolic genes, which are related to building molecules needed for healing. By contrast, larger applied forces, such as those that would occur with repetitive trotting, decreased expression of these anabolic genes. For female samples, however, the amount of force applied did not influence the level of anabolic gene expression.

“It didn’t matter whether there was low, medium or high activity for females,” said Lauren Paschall, graduate student in biomedical engineering at Penn State and first author on the paper. “Female ACLs exposed to chronic use just didn’t heal as well as male ACLs, which may explain why women are predisposed to injuries. This supports the hypothesis that noncontact ACL injuries are attributed to microtraumas associated with chronic overuse that predispose the ACL to injury.”

According to the researchers, one explanation for the sex differences the team observed could be due to the higher amounts of oestrogen in females.

“Some studies have found that the overall effect of oestrogen on ACL injury is negative,” Paschall said. “Specifically, studies have shown that human women are more likely to tear their ACLs during the preovulatory phase, when oestrogen levels are high, than during the postovulatory phase, when oestrogen levels are low.”

She said the team plans to further investigate the role of oestrogen on ACL injury.

Szczesny noted that although the team’s study was not in humans, the findings may suggest that providing additional recovery time for women following injuries could be advantageous.

“Ultimately, this work could also help to identify targets for therapeutics to prevent ACL injuries in women,” he said.

Source: Penn State

Categories : Gender Metabolic DisordersTags :

Study Suggests Lowering Type 2 Diabetes Diagnosis Threshold in Women under 50

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New research published in the journal Diabetes Therapy suggests that the diagnosis threshold for type 2 diabetes (T2D) should be lowered in women aged under 50 years, since natural blood loss through menstruation could be affecting their blood sugar management.

Analysis of the national diabetes audit results has shown that women of younger age with type 2 diabetes mellitus (T2D) seem to have a higher mortality rate than men. The underlying mechanisms remain unclear. However, it is known that women are on average diagnosed with T2D at a later age than men. In this new study, the authors investigated whether a contributing factor to this late diagnosis may be a sex difference in the levels of glycated haemoglobin (HbA1c) due to haemoglobin replacement linked to menstrual blood loss.

This mechanism behind this could be shorter erythrocyte (red blood cell) survival which results in shorter exposure of haemoglobin to glucose compared with individuals who do not menstruate. Given that the diagnosis of T2D is also based on HbA1c, the use of the same reference range irrespective of age and sex, when a slightly lower point for T2D for premenopausal women may be appropriate, could potentially lead to under diagnosis of T2D in women and missed opportunities for intervention.

The study, by Dr Adrian Heald, Salford Royal Hospital, UK, and colleagues, examined HbA1c testing across seven UK laboratory sites (representing 5% of UK population). They conducted an exploratory analysis in two cohorts: cohort 1 was from one laboratory tested between 2012 and 2019 (146 907 participants). They assessed the sex and age differences of HbA1c in individuals who underwent single testing only, that had not been diagnosed with diabetes and had an HbA1c result of equal to or less than 48mmol/mol (the cutoff for diagnosing diabetes). The process was replicated in cohort 2 results from six laboratories with individuals tested between 2019 and 2021 (total people included 938 678). The possible national impact was estimated by extrapolating findings based on the Office of National Statistics (ONS) England population data and National Diabetes Audit published T2D prevalence and related excess mortality.

At age 50 years, average HbA1c levels in women lag by approximately five years compared to men. The data also show women aged under 50 years old had an HbA1c distribution that was lower than that of men by an average of 1.6mmol/mol (4.7% of the overall mean) while the difference in the distribution of HbA1c for individuals aged 50 years and over was less pronounced.  Further analysis showed that, at HbA1c of 48mmol/mol, 50% fewer women could be diagnosed with T2D than men under the age of 50, whilst only 20% fewer women could be diagnosed with T2D than men over or equal to the age of 50. These findings were consistent with those in cohort 2.

Based on these observations, the authors estimated the effects of lowering the threshold for diagnosis of diabetes from HbA1c (48mmol/mol) by 4.2% to 46mmol/mol for women under the age of 50. This analysis showed that an additional 35 345 currently undiagnosed women in England would be reclassified as being diagnosed with T2D (17% more than the current 208 000 recorded women with T2D aged under 50 years). Lifestyle changes and treatment for diabetes would then be initiated for these women enabling improvement in health outcomes over both the short and longer term.

The authors also highlight that sex and gender difference in adverse cardiovascular risk factors are known to be present prior to the development of T2D. Once diagnosed, the prevalence of atherosclerotic cardiovascular disease is twice as high in patients with diabetes mellitus compared to those without diabetes mellitus. For women, diabetes mellitus is a stronger risk factor for cardiovascular disease than for men: women with diabetes aged 35–59 years have the highest relative cardiovascular death risk across all age and sex groups.

Furthermore, there is disparity in cardiovascular risk factor management between men and women, including in high-risk groups such as women with T2D.  Women are less likely than men to receive treatment and cardiovascular risk reduction interventions that are recommended by international guidelines on diabetes. In addition, concordance with medication or prescription treating cardiovascular risk factors is lower in women than men with T2D, with less use of statins, aspirin and beta blockers. The authors say taken together, these factors mean “timely diagnosis of type 2 diabetes and initiation of preventative treatment has the potential to improve cardiovascular risk profile over lifetime and facilitate longer life quality and expectancy in women. Our findings provide evidence that the HbA1c threshold for this group should be re-evaluated.”

Source: EurekAlert!