New Study Reveals Faecal Metabolite Signature Linked to Prediabetes and Type-2 Diabetes 

18th October 2023 – by Aaruthy Suthahar

Researchers from TwinsUK have recently identified eight biochemical compounds measured in stool (faecal metabolites) that are involved in prediabetes and type-2 diabetes risk in a large study. Impaired fasting glucose, also known as prediabetes, refers to elevated blood sugar levels that are not high enough to mean that the person has type.2 diabetes. Most importantly, prediabetes is a reversible condition: you can prevent or delay prediabetes from turning into type-2 diabetes with well-established lifestyle changes. However, over 80% of individuals with prediabetes remain unaware of their condition. Previous research found a link between type-2 diabetes, prediabetes and the bacteria living in our gut, but mechanisms remain elusive.  Faecal metabolites can provide valuable insights into their metabolic health, as they are the result of various metabolic processes occurring in the body, including the digestion and breakdown of food, as well as the activities of gut bacteria. 

The team analysed the gut microbiome and blood glucose levels collected from 1,018 TwinsUK participants, and then checked their findings in an additional cohort from Germany. The researchers discovered eight specific faecal metabolites linked to prediabetes risk. Importantly, though these metabolites were chemicals or substances that are not naturally found in the body and come from outside sources, they were still reflective of the individuals’ gut bacteria, suggesting a complex interplay between the gut microbiome and the host’s metabolic processes. Moreover, these metabolites were also predictive of type-2 diabetes in a sub-analysis, showing a potential connection with the development of type-2 diabetes. 

First author Ana Nogal stated: 

“Our findings open up new avenues for understanding the role of the gut microbiome in prediabetes and type-2 diabetes. The gut microbiome seems to influence the intestinal absorption or excretion of compounds that are not produced by the human body, and this is linked to prediabetes risk, adding another layer to the complex web of interactions between the gut microbiota and metabolic health.” 

Senior author Cristina Menni explained: 

“This research has the potential to transform our understanding of prediabetes and type-2 diabetes development, offering new insights into the role of the gut microbiome. The implications of this study are far-reaching, and it has the potential to pave the way for innovative treatments and preventive measures for these prevalent metabolic conditions.” 

The study highlights the importance of considering the gut microbiome’s impact on the absorption and excretion of compounds in understanding the onset of type-2 diabetes. Further research is needed to explore this mechanism and its potential implications for diabetes prevention and management. 

Groundbreaking Insights into Predictive Metabolites of Heart Attacks 

11th October 2023 – by Aaruthy Suthahar

In a groundbreaking collaborative effort encompassing six intercontinental cohorts including TwinsUK, the Consortium of Metabolomics Studies (COMETS) has identified 10 novel molecules measured in serum that were associated with incident myocardial infarction (MI), commonly known as a heart attack. This research, representing the largest of its kind, included 7,897 people and has far-reaching implications for identifying at-risk individuals before the onset of this life-threatening condition. 

MI is a leading global cause of death and disability, underscoring the importance of early prediction and intervention. Previous studies measuring hundreds of serum molecules to identify biomarkers of MI have been restricted by limited participant numbers and/or demographic diversity. However, COMETS’ extensive research has addressed these limitations. 

In this study, individuals averaging 66 years of age were drawn from six distinct international cohorts, with their blood metabolomes analyzed. Coupled with data on 1,373 MI cases, the researchers executed a two-stage Individual Patient Data meta-analysis. 

The results were nothing short of groundbreaking. 56 metabolites, including 21 lipids and 17 amino acids, were linked to incident MI, with 10 of them not being reported before notably, the carbohydrate mannitol/sorbitol emerged with the highest increased risk, while glutamine exhibited the most significant decrease in risk. 

Moreover, these identified metabolites were substantially enriched in pathways previously associated with cardiovascular diseases, such as aminoacyl-tRNA biosynthesis. This reinforces the potential clinical relevance of these biomarkers. 

Senior author Cristina Menni explained:  

‘The identified molecules offer a promising avenue for early detection and risk assessment before the onset of heart disease. This is a significant breakthrough in cardiovascular research, as it can potentially enable healthcare professionals to identify individuals at risk of heart attacks well in advance, allowing for proactive interventions and personalized healthcare strategies.’ 

First author Ana Nogal said: 

‘The implications of this study are profound. The identified metabolites could serve as powerful tools for identifying individuals at high risk of MI before the disease manifests clinically. As a result, this research not only advances our comprehension of the molecular changes underlying MI development but also opens new avenues for clinical prediction and a more profound understanding of causal mechanisms.’ 

In a world where heart attacks remain a major public health concern, COMETS’ collaborative effort signifies the importance of multidisciplinary research and holds the promise of uncovering universal biomarkers that can save countless lives. 

TwinsUK successful in bid for multi-million-pound award for resilience research

Tuesday 3rd October – by Paz García

Older, grey-haired man and woman holding hands facing away from the camera

We are delighted to announce that TwinsUK has received a multi-million-pound funding award to study resilience in health and ageing through Wellcome Leap’s Dynamic Resilience programme, jointly funded by Temasek Trust. 

Led by TwinsUK’s Clinical Director Professor Claire Steves, the award will see TwinsUK invite 2,000 twins for clinic visits to collect post-pandemic health data and samples through a study named Resilience after COVID-19. The team will then analyse these together with data collected before and during the pandemic to further investigate known and suspected sources of resilience in the body. 

Resilience is the capacity to withstand or bounce back quickly from difficulties, including stressors and disease. The COVID-19 pandemic was a major stressor for everyone during 2020-2022, both in terms of the disease itself as well as the wider impact on wellbeing due to lockdowns and shielding mandates.    

The Resilience after COVID-19 study at TwinsUK will allow researchers to understand how certain processes in the body – including inflammation, changes to the microbiome and altered metabolism – affect resilience, using the twin design to control for and unpick genetic and environmental contributions. This in turn will help identify sources of resilience which can be targeted to promote healthy ageing. 

Professor Claire Steves said: 

“As the world population gets older, we need to find ways of protecting ourselves and ensuring we are healthier for longer. One way of doing that is to understand what makes us resilient, and that is what we’re aiming to achieve through this research programme.  

“This work is only possible thanks to our twins’ dedication and contributions over many years before and during the pandemic, providing samples and answering questionnaires.  

“Eligible TwinsUK members will be invited to take part in the Resilience after COVID-19 study over the next three years, so do keep an eye on your inbox.”  

In addition, the Dynamic Resilience programme has also funded research at the University of Birmingham, in which collaborators at King’s College London will study blood and stool samples collected before and after cancer patients undergo treatment. They will use computational learning methods to understand how changes in hallmarks of ageing relate to clinical changes and how such changes could be developed as predictive biomarkers of resilience. 

We are thrilled that TwinsUK has been recognised as a world leader in this field and we look forward to contributing to essential work on resilience through these two awards. 

Study Reveals Higher BMI Puts Adolescents at Risk for Depression 

5th September 2023 – by King’s College London

Children between the ages of 12 and 16 with a higher body mass index (BMI) are more susceptible to developing symptoms of depression, according to a recent study conducted by researchers from TwinsUK. The findings emphasize the importance of understanding the connection between mental health and weight in adolescence and suggest that early intervention strategies could be beneficial. 

The research, published in Psychological Medicine, used data from over 10,000 twins participating in the Twins Early Development Study (TEDS) and our TwinsUK cohort. Twins born between 1994 and 1996 self-reported depressive symptoms, including low mood, loneliness, and exhaustion, at ages 12, 16, and 21. The study’s key findings indicate a significant link between higher BMI and depression among individuals aged 12 to 16, with weaker association in the 16 to 21 age group. 

The team also found that children with a higher BMI during early adolescence were at an increased risk of developing depression later in life than those who experienced depression first and then saw an increase in their BMI.  

First author, Dr. Ellen Thompson explained: 

“Understanding the relationship between mental ill-health and weight in adolescence is vital to provide timely support where needed. This study shows a stronger association between having a higher BMI at age 12 years and subsequent depression symptoms at age 16 years than the reverse.” 

The study also highlighted that environmental factors played a significant role in the connection between BMI and depression at each age. While the study did not delve into the specific reasons for this effect, prior research has suggested that factors like body dissatisfaction and weight-related stigma from external sources could contribute to the association. 

Surprisingly, the study’s results remained consistent even after adjusting for socio-economic status, dispelling the notion from previous research that poverty might be the primary risk factor in this relationship. 

This shows the importance of early adolescence as a crucial period for addressing the potential consequences of higher BMI on mental health. Preventative measures, such as support structures and positive body image messages, could be incorporated into Personal, Social, Health and Economic (PSHE) education to counteract depressive symptoms in young teens. 

Co-senior author, Professor Claire Steves said: 

“Using the TwinsUK cohort, which focuses on older adult twins, our study showed that the relationship between BMI and depression was much weaker in later life. The exact reasons for these changes over the life course need further investigation.” 

Some people’s brain function still affected by Long COVID years after infection 

21st July 2023 – by King’s College London

Researchers from TwinsUK have found that people with longer-term COVID-19 symptoms including brain fog showed reduced performance in tasks testing different mental processes up to two years after infection with the virus.  

The team looked at whether infection with COVID-19 affected performance in two rounds of online cognitive testing that took place in 2021 and 2022. Data was collected for over 3,000 participants of the COVID Symptom Study Biobank study, across 12 tasks that tested memory, attention, reasoning, processing speed and motor control.  

The participants whose test scores were most affected by COVID-19 were those who had experienced symptoms related to the virus for 12 weeks or more. In these people, the effect of COVID-19 on test accuracy was comparable in size to the effect of a 10-year increase in age.  

There was no significant improvement in these test scores between the two rounds of testing, which took place nine months apart. By the second round of testing, the average time since participants’ initial COVID-19 infection was almost two years.  

Digging deeper into the analysis, the researchers separated participants by whether they felt fully recovered following COVID-19 infection. People who felt fully recovered after COVID-19 infection performed similarly to those who had not had the virus at all. In contrast, participants who did not feel fully recovered after infection had lower task accuracy scores on average.  

Lead author Dr Nathan Cheetham said: 

“Our findings suggest that, for people who were living with long-term symptoms after having COVID-19, the effects of the coronavirus on mental processes such as the ability to recall words and shapes are still detectable at an average of almost two years since their initial infection.  

“However, the result that COVID had no effect on performance in our tests for people who felt fully recovered, even if they’d had symptoms for several months and could be considered as experiencing ‘long COVID’, was good news. This study shows the need to monitor those people whose brain function is most affected by COVID-19, to see how their cognitive symptoms continue to develop and provide support towards recovery.”  

Professor Claire Steves added: 

“We used sensitive tests to measure speed and accuracy across a range of brain challenges. This study shows that some individuals have measurable changes in these tests after COVID-19 going on for nearly two years. The fact remains that two years on from their first infection, some people don’t feel fully recovered and their lives continue to be impacted by the long-term effects of the coronavirus. We need more work to understand why this is the case and what can be done to help.” 

Artificial Intelligence helps human radiologists: detecting intervertebral disc degeneration in MRI scans 

20th June 2023 – by Daliya Guemri

artificial intelligence

Researchers from TwinsUK have recently published a systematic review and meta-analysis examining the current efficacy of artificial intelligence (AI) machine learning applications that read MRI scans of degenerate discs. Working in the pain research team under Professor Frances Williams at King’s College London, researchers are motivated to glean the latest insights in developments to low back pain causes or treatment. Low back pain is the lead cause of disability globally and can fundamentally reduce patient quality of life. Intervertebral disc degeneration is a main cause of low back pain and Williams’ team is heavily invested in pioneering research into causes, diagnoses and treatments for the condition.  

Disc degeneration is a normal part of aging, however sometimes it is accompanied by disabling pain and interventions are required. This systematic review and meta-analysis specifically focused on machine learning (ML) algorithms that read lumbar magnetic resonance imaging (MRI) scans. Assessing disc degeneration is a time-consuming endeavour for radiologists, accurate machine learning algorithms that could fulfill this task, would represent a huge saving of work hours for health services across the globe. Fully exploiting AI technology could allow efficiency in identifying lumbar disc degeneration as well as other spinal conditions, and speed triaging patients for surgery or physiotherapy treatments.  

The systematic review found several studies with a computer science research focus that reported machine learning algorithms could do the job of radiologists, or that their approach could lead to diagnostic technology. Unfortunately, much of this software is not rigorously tested and most of the included studies had small numbers of participants. A systematic review and meta-analysis aim to the contribution of several small studies, however lack of replication (running the algorithm again in a totally new group of scans) was another stark omission from most of the included studies.   

In science, the best type of research is validated in different groups of participants and run multiple times. This should be a standard practice for medical treatments or tools. However they found that generally, these algorithms were not validated, and reports of added benefit to the assessment of disc degeneration were concluded perhaps prematurely.  

The technology is exciting as it does offer a real promise to the future of MRI reading and spinal assessments and ultimately better outcomes in patients with low back pain.  

Authors Roger Compte and Isabelle Granville Smith explained: 

We suggest future research should incorporate several machine learning approaches, such as adding semi- and un-supervised learning to supervised learning approaches. MRIs inherently contain vast quantities of information; of which the human eye is only capable of gleaning part. Designing machine learning algorithms that better take advantage of MRI data arrays may be a means to progress their reliability and accuracy to be comparable to and may one day surpass human radiologists.

Three types of long-COVID for people experiencing symptoms for 12 weeks or more 

17th April 2023 – by King’s College London 

Coronavirus

The paper recently published in Lancet Digital Health identifies patterns among people infected with the wild-type, the first strain of SARS-CoV-2, and Delta and Alpha variants, among vaccinated and unvaccinated individuals. 

Researchers from TwinsUK analysed data of 1,459 individuals who have experienced ongoing symptoms for longer than 84 days, known clinically as post-covid syndrome or long COVID, from the ZOE Health Study. 

The analysis adds to emerging evidence that long COVID is not a homogenous illness and should have personalised treatment and care. The team recommend the findings to be used by researchers investigating why and how long-COVID occurs, healthcare services providers, as well for people living with long COVID. 

People with symptoms for 12 weeks or more fell into three main groups based on the types of symptoms they were experiencing. The largest group was characterised by a cluster of neurological symptoms such as fatigue, brain-fog and headache and was the most common subtype among alpha and delta variants. A second group experienced respiratory symptoms including chest pain and severe shortness of breath, which could point to lung damage. This was the largest cluster in the wild-type period when the population was unvaccinated. Finally, there were some people who experienced a diverse range of symptoms including heart palpitations, muscle ache and pain, and changes in skin and hair. 

Crucially, the data also suggested that the symptom types for people who did experience symptoms for 12 weeks or more were similar in vaccinated and unvaccinated people at least with variants which had these data. Existing data shows that the risk of long-COVID overall is reduced by vaccination. 

Professor Claire Steves explained:  

These data show clearly that post COVID syndrome is not just one condition but appears to have at several subtypes. Our findings matched with people’s experience living with long COVID. Understanding the root causes of these subtypes may help in finding treatment strategies. Moreover, these data emphasise the need for Long-COVID services to incorporate a personalised approach sensitive to the issues of each individual.” 

While these three subtypes were evident in all variants, additional symptom clusters were also identified which were subtly different between variants. These differences may not be due to variants themselves, but other factors which have changed across the pandemic, such as time of year, social behaviours, and treatments. 

Given that the data used was collected over an interval of time, the study is relevant for post-COVID predictions, indicating how long certain symptoms could last. These insights could aid in the development of personalised diagnosis and treatment for these individuals. 

Diet high in protein linked with loss of muscle 

9th March 2023 – by Aaruthy Suthahar

beans and lentils

Researchers from TwinsUK have found that rather than being protective, high protein intake is associated with loss of muscle mass in healthy over-60s

This surprising finding comes from a study of 3,302 twins from the TwinsUK cohort. 

Sarcopenia is associated with ageing and occurs when there is an accelerated loss of skeletal muscle mass and function. This can lead to negative outcomes such as frailty, reduced function in day-to-day activities, and increased risk of falls. The study aimed to investigate factors linked with skeletal muscle strength, mass and sarcopenia, particularly intake of protein, and to evaluate if shared twin characteristics are important. 

The team studied twins who consumed the optimal recommended protein intake as the reference group (1.0–1.3 g/kg/day) and found that there was no significant link between protein intake (neither high nor low) and low muscle strength, or between low intake of protein and sarcopenia. 

Results showed that high protein intake on the other hand was associated with decreased muscle mass, while low protein intake was protective. High protein intake was also linked with sarcopenia, even after adjusting for demographic, anthropometric (physical measures of a person’s size, form, and functional capacities) and dietary factors. 

The study also found that the strength of muscles is linked with age, education, income, diet, appetite and diversity in the gut microbiome. However, the link between muscle strength and weight, body mass index, healthy eating index, protein intake, and gut microbiome diversity were not significantly influenced by shared twin factors. This means that treatments targeting these factors may be effective in preventing or treating sarcopenia. 

First author Dr Mary Ni Lochlainn explains: 

“We know high quality protein intake is essential for muscle health, however, it is important to consider that not all sources of protein contain the full range of essential amino acids, and that it may be important to eat some sources of protein in moderation.” 

“While our participants were healthy volunteers, the results give valuable insight into the link between diet and sarcopenia. Further research is needed to investigate this further, including looking at longitudinal data in cohorts with an increased number of participants who live with sarcopenia.” 

Can use of proton pump inhibitors increase your risk of fractures?

1st February 2023 – by Aaruthy Suthahar

Researchers from TwinsUK have found that taking proton pump inhibitors is linked with decreased hip bone density and this effect is partly mediated through plasma metabolites

This could put people at increased risk of fractures. 

Proton pump inhibitors (PPI) are common drugs used to treat gastric disorders and are one of the most used drugs in the UK. They decrease the release of acids in the stomach by blocking an enzyme which controls the production of acids. Acids in the gut microbiome are important for the absorption of a variety of nutrients like vitamins, iron, and calcium. Several studies have suggested that the use of PPI causes a lower absorption of intestinal calcium that could then lead to a decrease in bone mineral density (BMD) and increased fracture risk. 

The team wanted to investigate if PPI could modulate BMD by altering gut environment by using data from over 5,000 British male and female participants from the TwinsUK cohort.  

They observed a decrease in total hip BMD in individuals who used PPI. This effect however was not mediated through the gut microbiome, suggesting that the gut microbiome does not play a role in PPI’s effect on BMD.  

PPI users have lower plasma level of androgen sulfates, which belong to the sex hormone pathways. Besides, plasma androgen sulfate levels were associated with total hip BMD. Mediation analysis suggested that PPI could affect hip BMD indirectly through these plasma metabolites, providing a possible new mechanism.  

First author Xinyuan Zhang said: 

“In this study we showed that plasma metabolites could play a role in one of PPI’s major side effects, which is lowering BMD and increasing fracture risks. Our observation on the potential involvement of the androgen pathways in bone loss deserve additional investigations.” 

How much of a boost do “booster” COVID-19 jabs give?

26th January 2022 – By Aaruthy Suthahar

Scientists have found the “booster” COVID-19 vaccine programme led to a large boost in the antibodies that help protect against coronavirus. High levels of antibodies is associated with lower risk of severe infection.

The study, which is part of the National Core Study for Longitudinal Health and Wellbeing, is published today in the scientific journal eLife. Researchers from King’s College London, Bristol University, UCL and several other institutions around the UK teamed up to work on the project.

Researchers analysed blood samples from 9,361 participants from two UK population cohorts, with 4,739 participants from TwinsUK and 4,622 from Children of the 90s (also known as the Avon Longitudinal Study of Parents and Children). Samples were tested to measure antibodies generated by vaccination, and examine whether certain groups were more likely to have lower levels of antibodies. Lower levels are known to be linked to higher risk of coronavirus infection.

Similar to previous research, the study found higher infection rates among participants with lower levels of antibodies after a first vaccination. However, researchers also found large increases in antibodies with each round of vaccination. The level of antibodies was around 10 times higher in the first weeks after a third vaccine compared to those who had only received two vaccinations an average of six months earlier.

Some groups of individuals had consistently lower levels of antibodies after vaccination. In particular, people advised to “shield” in the first year of the COVID-19 pandemic because of an increased risk of complication due to COVID-19 were more likely to have fewer antibodies. The good news was that even these individuals mounted a strong response to the booster.

Researchers also found a third dose appeared to eliminate a key difference in antibody levels based on the type of vaccine received. While people who received the Oxford/AstraZeneca vaccine were more likely to have lower antibody levels than those who received Pfizer-BioNTech after one or two vaccinations, this difference was no longer present after a third vaccination.

Findings also showed people who had a confirmed coronavirus infection before vaccination were more likely to have higher levels of antibodies, compared to those without confirmed infection.

First author Dr Nathan Cheetham explained:

“ Our findings support a policy of a third (and now fourth) COVID-19 vaccination to boost antibodies and protect against COVID-19. This is especially true for people who had the Oxford/AstraZeneca vaccine for their first and second jabs. ”

“ Our results also showed that some people are more likely to have a weaker response to vaccination than others, which we hope will be useful for policy-makers when considering any future COVID-19 vaccinations. In particular, we saw in participants from both TwinsUK and Children of the 90s cohorts that the “Shielded Patient List” criteria were an effective means to identify those with lower response to vaccination, despite the guidance to shield no longer being in place. ”

Professor Claire Steves said:

“We were particularly pleased to see that individuals at higher risk of severe infection still responded well to the booster vaccination. This is further evidence that coming forward for a booster vaccination is a good idea as COVID is still very much around.”

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