Tag: 25/7/25

Categories : Cardiovascular Disease Metabolic DisordersTags :

Study Finds Higher Cardiovascular Risk for One Particular Sulfonylurea

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Photo by Stephen Foster on Unsplash

New research from investigators at Mass General Brigham suggests that a commonly used type 2 diabetes medication is linked to a higher rate of heart-related conditions compared to medications that hit other targets. The study examined nationwide data from nearly 50,000 patients treated with different sulfonylureas and found that glipizide – the most widely used drug in the US within this category, but not available in South Africa – was linked to higher incidence of heart failure, related hospitalisation and death compared to dipeptidyl peptidase-4 (DPP-4) inhibitors. Results are published in JAMA Network Open.

“Patients with type 2 diabetes are at heightened risk of adverse cardiovascular incidents such as stroke and cardiac arrest,” said corresponding author Alexander Turchin, MD, MS, of the Division of Endocrinology at Brigham and Women’s Hospital (BWH), a founding member of the Mass General Brigham healthcare system. “While sulfonylureas are popular and affordable diabetes medications, there is a lack of long-term clinical data on how they affect cardiac health in comparison to more neutral alternatives like dipeptidyl peptidase 4 inhibitors.”

Turchin and co-authors emulated a target trial by analysing electronic health records and insurance claims data from the BESTMED consortium. The cohort included 48 165 patients with type 2 diabetes and moderate cardiovascular risk who received care at 10 different study sites across the country, including BWH, as well as those covered by two different national health insurance plans.

The researchers studied the five-year risk of major adverse cardiovascular events in patients treated with different sulfonylureas (glimepiride, glipizide or glyburide) or DPP4i in addition to metformin, a primary diabetes medication. They found that glipizide was associated with a 13% increase in cardiovascular risk when compared to DPP4i, while glimepiride and glyburide led to relatively smaller and less clear effects, respectively. The authors propose that further research is needed to uncover the underlying mechanisms.

“Our study underscores the importance of evaluating each drug in a particular pharmacological class on its own merits,” said Turchin. 

Source: Mass General Brigham

Categories : Cancer GeneticsTags :

Women of African Ancestry May Be Biologically Predisposed to Early-onset or Aggressive Breast Cancers

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Photo by National Cancer Institute

While the incidence of breast cancer is highest for white women, Black women are more likely to have early-onset or more aggressive subtypes of breast cancer, such as triple-negative breast cancer. Among women under 50, the disparity is even greater: young Black women have double the mortality rate of young white women.

Now, research from the University of Notre Dame is shedding light on biological factors that may play a role in this disparity. The study published in iScience found that a population of cells in breast tissues, dubbed PZP cells, send cues that prompt behavioural changes that could promote breast cancer growth.

Funded by the National Cancer Institute at the National Institutes of Health, the study set out to explore what biological differences in breast tissue could be related to early onset or aggressive breast cancers. Most breast cancers are carcinomas, or a type of cancer that develops from epithelial cells. In healthy tissue, epithelial cells form linings in the body and typically have strong adhesive properties and do not move.

The researchers focused on PZP cells as previous studies had shown that these cells are naturally and significantly higher in healthy breast tissues of women of African ancestry than in healthy breast tissues of women of European ancestry. While PZP cell levels are known to be elevated in breast cancer patients in general, their higher numbers in healthy, African ancestry tissues could hold clues to why early-onset or aggressive breast cancers are more likely to occur in Black women.

“The disparity in breast cancer mortality rates, particularly among women of African descent, is multifaceted. While socioeconomic factors and delayed diagnosis may be contributing factors, substantial emerging evidence suggests that biological and genetic differences between racial groups can also play a role,” said Crislyn D’Souza-Schorey, the Morris Pollard Professor of Biological Sciences at Notre Dame and corresponding author of the study.

The study showed how PZP cells produce factors that activate epithelial cells to become invasive, where they detach from their primary site and invade the surrounding tissue.

For example, a particular biological signaling protein known as AKT is often overactive in breast cancers. This study showed that PZP cells can activate the AKT protein in breast epithelial cells, which in part allows them to invade the surrounding environment. PZP cells also secrete and deposit certain proteins outside the cell that guide the movement of breast epithelial cells as they invade.

Overall, the results of the study emphasize multiple mechanisms by which PZP cells may influence the early stages of breast cancer progression and their potential contribution to disease burden.

The researchers also looked at how a targeted breast cancer drug, capivasertib, which inhibits the AKT protein, impacted PZP cells and found it markedly reduced the effects of the PZP cells on breast epithelial cells.

“It’s important to understand the biological and genetic differences within normal tissue as well as tumours among racial groups, as these variations could potentially influence treatment options and survival rates. And consequently, in planning biomarker studies, cancer screenings or clinical trials, inclusivity is important,” said D’Souza-Schorey, also an affiliate of Notre Dame’s Berthiaume Institute for Precision Health and Harper Cancer Research Institute.

Source: University of Notre Dame

Categories : GeneticsTags :

US Self-reported Race and Ethnicity Are Poor Proxies of Genetic Ancestry

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Photo by ROCKETMANN TEAM

Genetic ancestry is much more complicated than how people report their race and ethnicity. New research, using data from the National Institutes of Health’s (NIH) All of Us Research Program, finds that people who identify as being from the same race or ethnic group can have a wide range of genetic differences. The findings are reported in the American Journal of Human Genetics, a Cell Press journal.

As doctors and researchers learn more about how genetic variants influence the incidence and course of human diseases, the study of genetic ancestry has become increasingly important. This research is driving the field of precision medicine, which aims to develop individualised healthcare.

People whose ancestors came from the same part of the world are likely to have inherited the same genetic variants, but self-identified race and ethnicity don’t tell the whole story about a person’s ancestors. NIH’s All of Us Research Program was created in part to address this puzzle and to learn more about how genetic ancestry influences human health.

In the current study, the investigators looked at the DNA of more than 230 000 people who have volunteered to share their health information for All of Us. They compared it to other large DNA projects from around the world using a technique called principal component analysis (PCA) to visualize population structure and help identify genetic similarity between individuals and groups of people. This analysis showed that people in the US have very mixed ancestry, and their DNA doesn’t always match the race or ethnicity they write on forms. Instead of falling into clear groups based on race or ethnicity, people’s genetic backgrounds show gradients of variation across different US regions and states.

This is especially significant for people who identify as being of Hispanic or Latino origin. These people have a wide-ranging blend of ancestries from European, Native American, and African groups. Importantly, genetic ancestry among these people varies across the US in part because of historic migration patterns. For example, Hispanics/Latinos in the Northeast are more likely to have Caribbean (and thus African) ancestry, and those in the Southwest are more likely to have Mexican and Central American (and thus Native American) ancestry.

One specific discovery was that ancestry was significantly associated with body mass index (BMI) and height, even after adjusting for socio-economic differences. For example, West and Central African ancestries were associated with higher BMI, whereas East Africa ancestry was associated with lower BMI. There were similar findings showing that people with ancestral origins from different parts of Europe have different body measurements including height, with northern European ancestry associated with greater height and southern European ancestry associated with shorter height. This suggests that subcontinental differences in ancestry can have opposite effects on biological traits and diseases.

This finding suggests that the subcontinental differences in ancestry between individuals can have opposite effects on biological traits, diseases, and health outcomes, emphasizing the importance of not classifying individuals into broad ancestry groups such as African, European, or Asian. Doing this will help to make this research more accurate and will help to improve the field of precision medicine.

Source: EurekAlert!

Categories : Metabolic Disorders Obstetrics & GynaecologyTags :

How Obesity also Affects the Next Generation

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Study reveals why children of obese mothers are more likely to develop metabolic disorders

Metabolites – from the mother permanently reprogram Kupffer cells. This changes their function, causes liver cells (hepatocytes) to accumulate fat and ultimately leads to a fatty liver. The graphic was created with BioRender.com (http://BioRender.com). © Image: AG Mass/University of Bonn

Children born to obese mothers are at higher risk of developing metabolic disorders, even if they follow a healthy diet themselves. A new study from the University of Bonn published in the journal Nature offers an explanation for this phenomenon. In obese mice, certain cells in the embryo’s liver are reprogrammed during pregnancy. This leads to long-term changes in the offspring’s metabolism. The researchers believe that these findings could also be relevant for humans.

The team focused on the so-called Kupffer cells. These are macrophages that help protect the body as part of the innate immune system. During embryonic development, they migrate into the liver, where they take up permanent residence. There, they fight off pathogens and break down ageing or damaged cells.

“But these Kupffer cells also act as conductors,” explains Prof Dr Elvira Mass from the LIMES Institute at the University of Bonn. “They instruct the surrounding liver cells on what to do. In this way, they help ensure that the liver, as a central metabolic organ, performs its many tasks correctly.”

Changing the tune: From Beethoven to Vivaldi

It appears, however, that it is this conducting function that is changed by obesity. This is what mouse experiments carried out by Mass in cooperation with other research groups at the University of Bonn suggest. “We were able to show that the offspring of obese mothers frequently developed a fatty liver shortly after birth,” says Dr Hao Huang from Mass’s lab. “And this happened even when the young animals were fed a completely normal diet.”

The cause of this disorder seems to be a kind of “reprogramming” of the Kupffer cells in the offspring. As a result, they send out molecular signals that instruct the liver cells to take up more fat. Figuratively speaking, they no longer conduct one of Beethoven’s symphonies but rather a piece by Vivaldi.

This shift already seems to occur during embryonic development and is triggered by metabolic products from the mother. These activate a kind of metabolic switch in the Kupffer cells and change the way these cells direct liver cells in the long term. “This switch is a so-called transcription factor,” says Mass. “It controls which genes are active in Kupffer cells.”

No fatty liver without the molecular switch

When the researchers genetically removed this switch in the Kupffer cells during pregnancy, the offspring did not develop a fatty liver. Whether this mechanism could also be targeted with medication is still unclear. The teams now plan to investigate this in follow-up studies.

If new treatment approaches emerge from this, it would be good news. The altered behaviour of the Kupffer cells likely has many negative consequences. Fat accumulation in the liver, for example, is accompanied by strong inflammatory responses. These can cause increasing numbers of hepatocytes to die and be replaced with scar tissue, resulting in fibrosis. At the same time, the risk that hepatocytes degenerate and become cancerous increases.

“It is becoming ever more evident that many diseases in humans already begin at a very early developmental stage,” says Mass, who is also spokesperson for the transdisciplinary research area “Life & Health” and a board member of the “ImmunoSensation2” Cluster of Excellence at the University of Bonn. “Our study is one of the few to explain in detail how this early programming can happen.”

Source: University of Bonn

Categories : Diet and Nutrition PaediatricsTags :

Consuming Certain Sweeteners May Increase Risk of Early Puberty

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Photo by Amit Lahav on Unsplash

Consuming certain sweeteners commonly found in foods and beverages may increase the risk of early puberty in children, particularly among those who are genetically predisposed, according to a study being presented Sunday at ENDO 2025, the Endocrine Society’s annual meeting in San Francisco, Calif. 

The researchers found that consuming aspartame, sucralose, glycyrrhizin and added sugars was significantly associated with a higher risk of early puberty, especially in children with certain genetic traits. The more of these sweeteners the teens consumed, the higher their risk of central precocious puberty.

“This study is one of the first to connect modern dietary habits – specifically sweetener intake – with both genetic factors and early puberty development in a large, real-world cohort,” said Yang-Ching Chen, MD, PhD, of Taipei Municipal Wan Fang Hospital and Taipei Medical University in Taipei, Taiwan. “It also highlights gender differences in how sweeteners affect boys and girls, adding an important layer to our understanding of individualised health risks.” 

A type of early puberty known as central precocious puberty is increasingly common. It can lead to emotional distress, shorter adult height, and increased risk of future metabolic and reproductive disorders.

Chen’s previous research found that certain sweeteners can directly influence hormones and gut bacteria linked to early puberty. For example, one artificial sweetener, acesulfame potassium or AceK, was shown to trigger the release of puberty-related hormones by activating “sweet taste” pathways in brain cells and increasing stress-related molecules. Another sweetener, glycyrrhizin (found in liquorice) was found to change the balance of gut bacteria and reduce the activity of genes involved in triggering puberty. 

“This suggests that what children eat and drink, especially products with sweeteners, may have a surprising and powerful impact on their development,” Chen said.

The new findings come from the Taiwan Pubertal Longitudinal Study (TPLS), begun in 2018. The study included data from 1407 teens. Central precocious puberty was diagnosed in 481 teens. The researchers assessed teens’ sweetener intake through validated questionnaires and testing of urine samples. Genetic predisposition was quantified using polygenic risk scores derived from 19 genes related to central precocious puberty. Early puberty was diagnosed based on medical exams, hormone levels and scans. 

Sucralose consumption was linked to a higher risk of central precocious puberty in boys and consumption of glycyrrhizin, sucralose and added sugars was associated with a higher risk of central precocious puberty in girls.

“The findings are directly relevant to families, paediatricians and public health authorities,” Chen said. “They suggest that screening for genetic risk and moderating sweetener intake could help prevent early puberty and its long-term health consequences. This could lead to new dietary guidelines or risk assessment tools for children, supporting healthier development.”

Source: The Endocrine Society