Genetic Links Between Obesity and Autoimmune Diseases Identified in Large European Study
Key Takeaways:
- Large-scale genetic analyses have identified a substantial shared genetic basis between obesity and several autoimmune disorders in people of European ancestry.
- Dozens of shared genetic loci and genes appear to influence both body weight regulation and immune system function, particularly pathways involved in immune homeostasis.
- The findings suggest potential causal links between obesity and certain autoimmune conditions, with implications for future therapeutic strategies.
Overview of the study
A recent study published in the Journal of Translational Medicine has identified important genetic links between obesity and autoimmune disorders, shedding new light on why these conditions often co-occur. The research, led by Jiang and colleagues, focused on individuals of European ancestry and used large-scale genomic datasets to explore how shared genetic factors may influence both excess body weight and immune-mediated disease.
Obesity and autoimmune disorders represent a significant comorbidity burden, yet until now their shared genetic architecture has remained poorly understood. By applying advanced cross-trait genome-wide association study (GWAS) methods, the researchers aimed to uncover pleiotropic genetic variants – genes or loci that influence more than one trait – that may contribute to both conditions.
Study methods and analytical approach
The researchers conducted a comprehensive cross-trait analysis using GWAS summary data for obesity and 17 autoimmune diseases. Genetic correlations between traits were assessed using LD score regression and high-definition likelihood methods, allowing the team to quantify the extent to which obesity and autoimmune conditions share inherited risk.
To identify specific shared genetic loci, the team employed Stratified Pleiotropic Locus Mapping (PLACO), followed by Bayesian colocalization analyses to confirm whether obesity and autoimmune diseases truly shared the same causal genetic variants. Further analyses examined gene-level effects and tissue-specific heritability, while potential drug targets were prioritised using summary-based Mendelian randomisation (SMR).
In addition, immune co-localization techniques and bidirectional Mendelian randomisation were used to explore immunological mechanisms and to clarify potential causal relationships between obesity and autoimmune diseases.
Key genetic findings
The analysis identified eight autoimmune diseases with significant genetic correlations to obesity. In total, researchers discovered 10,324 pleiotropic single-nucleotide polymorphisms (SNPs), which mapped to 52 independent risk loci. Of these, nine loci were confirmed as shared causal variants through colocalization analysis.
Gene-level investigations revealed 133 unique pleiotropic genes. Notably, genes such as CLN3, SH2B1, and MMEL1 were highlighted and found to be enriched in biological pathways related to hematopoietic cell differentiation and immune homeostasis. These pathways are central to both metabolic regulation and immune function, reinforcing the biological plausibility of a shared genetic basis.
Tissue and immune cell involvement
Tissue-specific heritability analyses showed that shared genetic effects were most prominent in immune-related tissues, particularly the spleen, whole blood, and Epstein–Barr virus (EBV)-transformed lymphocytes. This finding further supports the role of immune system regulation in the overlap between obesity and autoimmune disease risk.
Immune co-localization analyses implicated six traits related to IgD+ CD38− B cell subsets as key pathological conduits. These immune cells may represent an important link between metabolic dysfunction and autoimmune processes.
Evidence of causal relationships
Using bidirectional Mendelian randomisation, the study provided evidence that obesity may play a causal role in the development of certain autoimmune conditions, including hypothyroidism, psoriasis, and multiple sclerosis. Conversely, an inverse causal association was observed between type 1 diabetes and obesity risk, suggesting a more complex and condition-specific relationship.
Implications and conclusions
In their conclusions, the authors state:
“This study demonstrates a robust shared genetic foundation between obesity and multiple autoimmune diseases, pinpointing specific pleiotropic loci, genes, and immune cell subsets.”
By identifying shared genetic mechanisms, the research provides a clearer mechanistic framework for understanding why obesity and autoimmune disorders frequently coexist. Importantly, these findings also highlight potential molecular and immunological targets for future therapeutic intervention, with the potential to address both metabolic and autoimmune disease pathways simultaneously.
Overall, the study represents a significant step forward in understanding the complex interplay between body weight regulation and immune system dysfunction, and it opens new avenues for research into integrated prevention and treatment strategies.
Read More
Obesity Independently Associated With Higher Rates of Tinnitus in US Adults, Large Population Study Suggests
Key Takeaways:
- Adults living with obesity were significantly more likely to report tinnitus than those without obesity, even after accounting for demographic, behavioural and psychological factors.
- Around one in five adults with obesity reported tinnitus, compared with approximately one in seven adults without obesity.
- The findings highlight metabolic health and body weight as potentially relevant, modifiable factors in the broader management of tinnitus.
A growing public health question
Obesity appears to be independently associated with a higher prevalence of tinnitus, according to a large, nationally representative study of adults in the United States published online on 2 November in Cureus.
The research was led by Ashir Ahtsham of Lahore General Hospital in Pakistan and examined whether obesity contributes to tinnitus prevalence beyond the influence of age, sex, mental health and other known risk factors. The analysis drew on data from the National Health and Nutrition Examination Survey (NHANES), a long-running survey designed to reflect the health of the US population.
Tinnitus, commonly described as ringing, buzzing or other sounds perceived in the absence of an external auditory stimulus, affects a substantial proportion of adults worldwide. While its causes are multifactorial and not fully understood, increasing attention has been given to the role of systemic and metabolic health in its development and persistence.
How the study was conducted
The researchers performed a cross-sectional analysis using de-identified data from the NHANES 2015–2016 and 2017–2018 survey cycles. These two cycles were combined in line with established analytic guidance to improve statistical power.
After excluding individuals under the age of 20 and those with missing data on body mass index or tinnitus, the final analytic sample included 5,452 adults aged 20 years and older. Obesity was defined using standard criteria, with a body mass index of 30 kg/m² or higher.
Tinnitus was assessed through self-report. Participants were classified as having tinnitus if they reported experiencing ringing, buzzing or other noises in their ears lasting five minutes or more in the absence of an external sound.
To isolate the association between obesity and tinnitus, the researchers adjusted their analyses for a range of potential confounders, including age, sex, race and ethnicity, smoking status, sleep duration and symptoms of depression, assessed using the Patient Health Questionnaire-9. Hearing loss data were not included, as this would have substantially reduced the available sample across both survey cycles. Readers interested in the detailed methodology can refer directly to the journal article.
Tinnitus was common, particularly among people with obesity
Across the full sample, 863 participants reported tinnitus, corresponding to a weighted prevalence of 17.2 percent. Tinnitus was more frequently reported by older adults, men and individuals living with obesity or depression.
Notably, the prevalence of tinnitus differed markedly by obesity status. Around 20.3 percent of adults with obesity reported tinnitus, compared with 15.0 percent of adults without obesity. This difference remained statistically significant at the population level.
Age was also a strong factor. Tinnitus prevalence increased steadily with age, rising from just over 10 percent in adults aged 20–39 years to nearly one quarter of those aged 60 years and older. Differences were also observed across racial and ethnic groups, with non-Hispanic White adults reporting the highest prevalence.
Obesity remained a significant predictor after adjustment
In unadjusted analyses, obesity was associated with a 44 percent higher likelihood of reporting tinnitus. Importantly, this association persisted even after accounting for demographic characteristics, lifestyle factors and depression.
After full adjustment, adults living with obesity still had approximately 41 percent higher odds of reporting tinnitus than adults without obesity. The strength and consistency of this association suggest that obesity may contribute to tinnitus prevalence independently, rather than simply reflecting shared risk factors such as age or mental health.
As the authors note, “These findings underscore the potential role of body weight and metabolic health in the development or progression of tinnitus.” They add that, “The substantial burden of obesity in recent years and its association with tinnitus highlight the importance of considering modifiable metabolic risk factors as part of comprehensive tinnitus management.”
Why might obesity and tinnitus be linked?
Although the study was not designed to explore biological mechanisms directly, the authors outline several plausible pathways supported by existing research.
Obesity is characterised by chronic low-grade inflammation, metabolic dysregulation and vascular dysfunction. These processes may impair microcirculation within the cochlea and disrupt normal auditory signalling. Excess adipose tissue is also known to produce pro-inflammatory cytokines, which may contribute to oxidative stress and neural inflammation affecting auditory pathways.
In addition, obesity is frequently associated with metabolic syndrome, insulin resistance and sleep disorders, all of which have been independently linked to tinnitus severity and distress. Together, these factors may help explain why people living with obesity experience tinnitus more frequently, even in the absence of measured hearing loss.
Strengths and limitations
A key strength of this study is its use of a large, nationally representative dataset with appropriate weighting to reflect the US population. The analysis also accounted for a wide range of demographic, behavioural and psychological variables.
However, the authors emphasise that the cross-sectional design means causality cannot be inferred. Tinnitus was self-reported, which may introduce recall or reporting bias. Important factors such as occupational noise exposure, medication use and audiometric hearing thresholds were not included, and these may partially mediate the observed association.
For readers seeking detailed statistical outputs or subgroup analyses, the original journal article provides comprehensive tables and supplementary information.
Implications for clinical practice and future research
The findings suggest that obesity is independently associated with tinnitus among US adults, reinforcing the view that tinnitus should be considered within a broader framework of systemic and metabolic health.
While weight reduction cannot currently be recommended as a specific treatment for tinnitus, the results support the inclusion of metabolic risk assessment as part of holistic tinnitus care. Building the confidence to assess and manage excess weight as part of that broader, whole-person picture is the focus of professional training such as the College of Contemporary Health’s Obesity Essentials, a CPD-accredited online short course. Further longitudinal studies, particularly those incorporating objective hearing measures, are needed to clarify causal pathways and to determine whether improvements in metabolic health could reduce tinnitus risk or severity.
As the burden of both obesity and tinnitus continues to rise globally, understanding how these conditions intersect may help inform more comprehensive and person-centred approaches to prevention and management.
CCH insight
Findings like these are a reminder that obesity rarely acts in isolation – its metabolic and inflammatory effects can reach into unexpected areas of health. CCH’s Obesity Essentials CPD short course (10 CPD hours, fully online, CPD-accredited) helps healthcare professionals understand these wider systemic effects and build the practical skills to assess and manage patients with overweight and obesity as part of holistic, person-centred care.
Explore Obesity Essentials →
More Than One in Four Adults Worldwide May Be Eligible for GLP-1 Weight-Loss Medicines, Global Analysis Suggests
Key Takeaways:
- More than 27 percent of adults globally may be eligible for GLP-1 receptor agonists for weight management, based on pooled data from 99 countries.
- Eligibility is highest among women, older adults, and people living in low- and middle-income countries, raising significant questions around access and health equity.
- Researchers emphasise that medicines alone are not sufficient, and sustained investment in prevention and non-pharmacological obesity care remains essential.
A growing global obesity challenge
The worldwide prevalence of obesity has more than doubled over the past three decades, accompanied by sharp rises in weight-related conditions such as type 2 diabetes, cardiovascular disease, and several cancers. This escalating public health challenge places increasing strain on healthcare systems and national economies across the globe.
Against this backdrop, a new international study suggests that glucagon-like peptide-1 receptor agonists, commonly referred to as GLP-1 medications, could play a substantial role in addressing obesity and its related complications at scale. The analysis was co-led by investigators from Mass General Brigham and aimed to estimate how many adults worldwide might benefit from these medicines.
Large-scale global data analysis
Researchers from Mass General Brigham collaborated with colleagues at Washington University School of Medicine in St. Louis and Emory University’s Rollins School of Public Health to pool household health survey data from 99 countries, collected between 2008 and 2021.
The final dataset included 810,635 adults aged 25 to 64 years, selected based on the availability of key clinical measures, including:
- Body mass index
- Blood pressure
- Diabetes biomarkers
- Diagnostic history of hypertension and diabetes
Eligibility for GLP-1 treatment was defined using established clinical thresholds. Adults were considered eligible if they had:
- A BMI greater than 30, or
- A BMI greater than 27 in the presence of hypertension, diabetes, or both
One in four adults eligible worldwide
Using these criteria, the researchers found that 27 percent of adults globally would be eligible for GLP-1 medications for weight management. Notably, around four-fifths of eligible individuals lived in low- and middle-income countries, highlighting a potential mismatch between need and access.
Eligibility varied substantially by region:
- Europe and North America showed the highest rates at 42.8 percent
- The Pacific Islands followed closely at 41.0 percent
Differences were also observed across demographic groups:
- Women were more likely to be eligible than men, at 28.5 percent versus lower rates among men
- Older adults showed markedly higher eligibility at 38.3 percent, compared with 17.9 percent among younger adults
The findings were published as a research letter in The Lancet Diabetes & Endocrinology.
Rethinking obesity through biology
Commenting on the findings, co-senior author Jennifer Manne-Goehler, MD, ScD, a physician at Brigham and Women’s Hospital and Mass General Brigham, highlighted the paradigm shift represented by GLP-1 therapies.
“There has never been such a potentially transformational and scalable tool for obesity, type 2 diabetes, and other health-related complications of obesity.”
She also reflected on the historical framing of obesity as a personal failing rather than a biologically driven disease.
“For so many decades, we told everyone the problem was you – you need to move more and eat less, then you will not struggle with this problem. GLP-1 receptor agonists have allowed us to really understand that biology is much more powerful than that, and ‘eat less, move more’ is just an oversimplified way to think about things.”
Global interest meets practical constraints
The potential of GLP-1 medicines has already been recognised by the World Health Organization, which is actively exploring ways to make these treatments more widely available as standard therapies. However, translating this promise into real-world impact depends on understanding the scale of need and addressing significant barriers to access.
Corresponding author Sang Gune K. Yoo, MD, who conducted the work while a research fellow in cardiology at Washington University School of Medicine, noted that the findings were consistent with global obesity trends.
“Given the steadily increasing prevalence of obesity, it is not surprising that our analysis found that more than one quarter of adults around the world may be eligible for this medication.”
He cautioned, however, that important questions remain unanswered.
“This medication has the potential to help many individuals, although further research is needed to better understand its long-term safety and sustainability. Access remains a major challenge as these medications are difficult to obtain in many settings. Most importantly, we must continue to invest in and develop effective non-pharmacological strategies for the prevention and treatment of obesity, an area where substantial gaps remain.”
Equity at the centre of global implementation
The study also underscores profound equity considerations. Eligibility was disproportionately high among women and people living in regions with limited healthcare resources.
Manne-Goehler highlighted the urgency of addressing these disparities.
“These socioeconomic and gender eligibility percentiles are especially staggering. As of last year, type 2 diabetes was the top cause of death for women in South Africa. There are parts of the world where women can really benefit from these medicines, and it is our job to see through their implementation.”
Co-lead author Felix Teufel, MD, from Emory University’s Rollins School of Public Health, framed access to GLP-1 therapies as a broader ethical issue.
“Global access to GLP-1s is a question of health equity. The goal is to ensure large-scale access for people who would benefit most – not just those easiest to reach.”
Beyond medicines alone
While the findings point to a potentially transformative role for GLP-1 medications in global obesity care, the authors stress that pharmacological approaches cannot replace comprehensive prevention and treatment strategies. Addressing obesity at scale will continue to require sustained investment in public health, supportive environments, and evidence-based, non-pharmacological interventions alongside new medical therapies.
CCH insight:
This study reminds us of the scale of the obesity pandemic. There are more than 1 billion people estimated to be living with obesity, according to the World Health Organisation – most of whom could in theory benefit from GLP-1 medications. The priority should be to provide access for those who are in greatest need, rather than those who can afford to pay for them. The development of oral GLP-1s is a big step, as this will increase access and bring prices down, but there is a very long way to go.
Read More
Abdominal Obesity Identified as a Key Risk Factor for Migraine in Young Adults, Large South Korean Study Finds
Key Takeaways:
- A nationwide cohort study of more than six million young adults found that obesity is associated with an increased risk of developing migraine over time
- Abdominal obesity, measured by waist circumference, was a stronger and more consistent predictor of migraine risk than overall body mass index
- The association was particularly pronounced in younger adults and appeared to be influenced by lifestyle factors such as alcohol consumption
A large longitudinal study conducted in South Korea has found that obesity, particularly abdominal obesity, is associated with a higher risk of developing migraine in young adulthood. The research suggests that fat distribution around the abdomen is a more important predictor of migraine onset than overall body weight as measured by body mass index. The findings were published in the medical journal Neurology.
Migraine is a disabling neurological disorder that places a substantial burden on individuals, healthcare systems, and society. While genetic predisposition plays a significant role in determining who develops migraine, environmental and lifestyle factors are also recognised contributors. In clinical practice, managing coexisting conditions is widely regarded as an important component of migraine care.
Obesity is already known to increase the severity and frequency of migraine attacks in people who live with the condition, a process often described as chronification. However, whether obesity contributes to the initial development of migraine in people without a prior history has remained less certain. Much of the existing evidence has been based on cross-sectional studies, which capture data at a single point in time and cannot establish the direction of cause and effect.
Moving beyond cross-sectional evidence
To address this limitation, the authors of the new study designed a large prospective cohort analysis to examine whether obesity precedes and increases the risk of migraine onset. Their primary objective was to assess the association between obesity and incident migraine, and to determine whether migraine risk increased in line with the severity of obesity. A further aim was to compare the predictive value of general obesity with that of abdominal obesity.
The researchers drew on data from the Korean National Health Insurance Service, which provides healthcare coverage for approximately 99 percent of the South Korean population. The analysis focused on adults aged 20 to 39 who underwent routine health examinations between 2009 and 2012.
The initial dataset comprised more than six million individuals. To ensure that only new cases of migraine were captured, the researchers applied rigorous exclusion criteria. Individuals with a prior diagnosis of migraine were removed, as were those with missing information on body measurements or lifestyle factors. To reduce the risk of including people with undiagnosed migraine at baseline, anyone diagnosed within the first year of follow-up was also excluded.
After these exclusions, the final study population included 6,106,560 participants. The average age was approximately 30 years, and around 39 percent of participants were female.
Long-term follow-up and detailed health data
Participants were followed from the date of their health examination until the end of 2018. New cases of migraine were identified using medical claims data, specifically the International Classification of Diseases code G43. The average follow-up period was seven years, allowing for robust assessment of long-term risk.
During health examinations, trained medical staff measured height, weight, and waist circumference while participants wore light clothing. Body mass index was calculated as weight in kilograms divided by height in metres squared. Body mass index was categorised into five groups, ranging from underweight to stage 2 obesity. Waist circumference was divided into six categories using 5 centimetre increments, enabling a detailed assessment of abdominal obesity.
The dataset also included extensive information on potential confounding factors. Participants completed questionnaires covering smoking status, alcohol consumption, physical activity, and income level. Blood tests provided measurements of cholesterol, glucose, and other metabolic markers, allowing for comprehensive statistical adjustment.
Abdominal fat emerges as a stronger predictor than body mass index
The analysis showed a clear association between obesity and the risk of developing migraine. In models that adjusted for age and sex, migraine risk increased progressively with higher body mass index, with individuals living with stage 2 obesity showing a higher likelihood of receiving a migraine diagnosis compared with those in the normal weight range.
However, the association was even more pronounced when abdominal obesity was examined. Waist circumference demonstrated a dose-dependent relationship with migraine risk, meaning that each incremental increase in waist size was associated with a stepwise rise in risk. This pattern persisted even after adjustment for a wide range of demographic, lifestyle, and metabolic factors.
When the researchers adjusted their models to account for waist circumference, the association between body mass index and migraine weakened. In contrast, the relationship between waist circumference and migraine remained strong even after body mass index was taken into account. This indicates that abdominal obesity functions as an independent risk factor for migraine, more influential than overall body weight.
Participants with the largest waist measurements had significantly higher hazard ratios for migraine, while those with the smallest waist circumferences showed a reduced risk.
Underweight status and the role of muscle mass
The study also explored the relationship between being underweight and migraine risk. Initial analyses suggested that underweight individuals might have an increased risk of migraine. However, this association disappeared after full statistical adjustment, indicating that low body weight alone is unlikely to be a direct cause of migraine.
More nuanced findings emerged when waist circumference was controlled for. Extremely low body mass index was associated with higher migraine risk, which the authors suggest may reflect low skeletal muscle mass rather than low fat mass. Skeletal muscle plays a role in modulating inflammatory processes, and reduced muscle mass may contribute to a pro-inflammatory state.
Inflammation as a plausible biological mechanism
Inflammation is widely considered a key biological link between obesity and migraine. Adipose tissue, particularly visceral fat stored deep within the abdominal cavity, is metabolically active and releases a range of pro-inflammatory cytokines and adipokines.
Visceral fat is known to produce higher levels of inflammatory mediators than subcutaneous fat. This distinction may explain why waist circumference was a more reliable predictor of migraine risk than body mass index. Chronic low-grade inflammation associated with excess abdominal fat could lower the threshold for migraine development and increase susceptibility to neurological sensitisation.
Differences by age and lifestyle factors
Subgroup analyses revealed that age modified the observed associations. The link between abdominal obesity and migraine was stronger in adults under 30 years of age than in those in their thirties. This suggests that younger adults may be particularly vulnerable to the neurological effects of excess abdominal fat.
Lifestyle factors also influenced the strength of the association. The relationship between abdominal obesity and migraine was more pronounced in non-smokers than in smokers, and stronger in people who consumed alcohol heavily. Alcohol is known to have vasodilatory effects and is a recognised migraine trigger.
The researchers proposed that alcohol use and obesity may have synergistic effects, with alcohol-related vascular changes interacting with obesity-driven inflammation to further increase migraine risk.
Study limitations and future directions
Several limitations should be considered when interpreting the findings. Because migraine cases were identified using health insurance claims, only individuals who sought medical care were included. Many people live with migraine without receiving a formal diagnosis, which may have led to an underestimation of true incidence.
The study population was limited to South Korea, and patterns of body composition and fat distribution vary across ethnic groups. As a result, the waist circumference and body mass index thresholds used in this study may not be directly applicable to other populations. The gender distribution was also uneven, reflecting the characteristics of the national screening programme.
As an observational study, the analysis cannot definitively establish causation. Although the temporal relationship between obesity and migraine onset was clear, unmeasured factors may still have influenced the results despite extensive statistical adjustment.
Future research is needed to confirm these findings in other populations and to explore the underlying biological pathways in greater detail. Studies examining specific inflammatory mediators and adipokines may help clarify how abdominal obesity contributes to migraine development.
Implications for migraine prevention
Despite its limitations, this large-scale study provides compelling evidence that maintaining a healthy body composition may play a role in preventing migraine, particularly in young adults. The findings emphasise that fat distribution, not just overall weight, is clinically relevant. For clinicians, assessing abdominal obesity may offer additional insight when evaluating migraine risk and discussing preventive strategies with patients.
Developing that assessment skill set – including looking beyond BMI to measures such as waist circumference – is the focus of professional training such as the College of Contemporary Health’s Obesity Essentials, a CPD-accredited online short course covering the assessment and management of overweight and obesity.
The study, Association Between Obesity and the Risk of Migraine: A Nationwide Cohort Study in South Korea, was authored by Soo-Im Jang, Namoh Kim, Kyungdo Han, and Mi Ji Lee.
CCH insight:
Yet another inflammatory condition linked to obesity! It is interesting to note that this study found waist circumference to be a much better predictor of migraine risk than BMI. This is because waist circumference is a better indicator of excess visceral fat, which produces high levels of pro-inflammatory mediators. So this is a reminder of the limitations of BMI and the importance of considering waist circumference or waist:height ratio when assessing the extent and impact of excess body weight when assessing the extent and impact of excess body weight. For practitioners wanting to sharpen that assessment skill set, CCH’s Obesity Essentials CPD short course (10 CPD hours, fully online, CPD-accredited) covers how to assess and manage patients with overweight and obesity using a rounded, evidence-based approach that goes beyond a single number on the scale.
Explore Obesity Essentials →
GLP-1 Weight-Loss Medications Linked to Fewer Severe Asthma Attacks in Adolescents with Excess Weight
Key Takeaways:
- Adolescents with excess weight and asthma who were prescribed GLP-1 medications experienced around half as many asthma-related emergency room visits over one year compared with peers not taking these drugs.
- Use of GLP-1 therapies was also associated with reduced reliance on steroids and rescue inhalers, suggesting improved asthma control.
- Researchers suggest these medicines may offer a dual benefit, supporting weight management while lowering the risk of asthma exacerbations in this population.
Study suggests dual benefit for weight and asthma control
Severe asthma attacks among adolescents with excess weight may be significantly reduced with the use of newer weight-loss medications such as Ozempic and Zepbound, according to a new observational study.
The research found that emergency room visits for asthma were cut by more than half among teenagers who were prescribed a glucagon-like peptide-1 (GLP-1) receptor agonist. The findings were reported on 29 December in JAMA Network Open.
“Our findings suggest a potential dual benefit for this population, where a single class of medication could address both weight management and lower risk for asthma exacerbation, thereby potentially reducing the burden of two common and interconnected chronic conditions,” the researchers concluded.
The study was led by Dr Lin‑Shien Fu, chief of paediatric nephrology and immunology at Taichung Veterans General Hospital.
How the study was conducted
Researchers followed 1,070 adolescents aged 12 to 18 years who were living with excess weight and had a clinical diagnosis of asthma. Approximately half of the group had been prescribed a GLP-1 medication, while the remainder had not received a weight-loss drug.
GLP-1 receptor agonists mimic the naturally occurring GLP-1 hormone, which plays a role in regulating insulin and blood glucose levels. These medicines also reduce appetite and slow gastric emptying, contributing to weight loss.
Over a 12-month follow-up period, the researchers recorded:
- Eight asthma-related emergency department visits among adolescents taking a GLP-1 medication
- Nineteen asthma-related emergency visits among those not prescribed a weight-loss drug
Reduced need for asthma medications
In addition to fewer emergency visits, adolescents taking GLP-1 medications were less likely to require other treatments for asthma control.
The study found that:
- 21% of adolescents taking a GLP-1 medication required steroid treatment for asthma, compared with 31% of those not taking the drugs
- 32% of adolescents in the GLP-1 group needed a rescue inhaler, compared with 45% in the non-GLP-1 group
These differences suggest an overall reduction in asthma severity and symptom burden among those prescribed GLP-1 therapies.
Weight loss and inflammation may explain the findings
Experts not involved in the research say the observed improvements are likely linked to the degree of weight loss achieved with these newer medications.
Dr Michelle Katzow, medical director of the POWER Kids Weight Management Program and associate professor of paediatrics at Cohen Children’s Medical Center in New York City, commented on the findings in a news release.
“I think it is not surprising and not so new, except for the degree of weight loss that the drug induces is so much bigger in magnitude than we have seen before,” she said.
Dr Katzow explained that excess weight contributes to systemic inflammation, which can worsen asthma symptoms and increase the likelihood of exacerbations.
“The sort of inflammation associated with obesity predisposes somebody to having worse asthma or worse symptoms of asthma,” she said.
“If you can help people lose enough weight by whatever means, then you can improve their asthma severity.”
Implications for adolescents struggling with appetite control
Dr Katzow added that GLP-1 medications may be particularly helpful for adolescents who struggle to adopt healthy behaviours because of persistent hunger.
She noted that this is a common challenge among young people with excess weight.
“And that is true for a lot of kids,” she said. “They are just really hungry and they are thinking about food a lot. Trying to make healthier choices or eat less is really hard to do if you are hungry all the time.”
A cautious but promising signal
While the study does not establish a direct causal relationship, it adds to growing evidence that weight-loss interventions can have meaningful benefits beyond body weight alone. The findings suggest that, for some adolescents living with excess weight and asthma, GLP-1 receptor agonists may help reduce the frequency and severity of asthma exacerbations alongside supporting weight management.
Further research will be needed to confirm these findings and to better understand the long-term safety and clinical role of GLP-1 therapies in paediatric populations.
CCH insight:
The long list of benefits of GLP-1 therapy continues to grow. If obesity increases the risk of asthma, it is not surprising that GLP-1 therapy results in a reduction in hospital visits due to asthma. Further studies are needed to back up these results, and also to see if the same benefits are seen in adults, as well as adolescents.
Read More
Bottle Feeding Toddlers to Sleep Linked to Tooth Decay and Excess Weight in Early Childhood
Key Takeaways:
- More than three in ten toddlers were still being bottle fed to sleep at two years of age
- Bottle feeding to sleep at age two was linked to almost double the risk of overweight in early childhood
- Continuing the practice at age three was associated with nearly twice as many teeth affected by decay
Parents and carers are being urged to avoid using bottles to help toddlers fall asleep, after new research found clear links between the practice, early childhood tooth decay, and excess weight gain.
The study, published in the Australian and New Zealand Journal of Public Health, was led by researchers at the University of Sydney and drew on data from more than 700 toddlers participating in Western Sydney University’s Healthy Smiles Healthy Kids (HSHK) cohort study. The long running study follows children from birth to examine factors influencing oral health and broader health outcomes.
Study design and data sources
Researchers analysed information collected through surveys completed by mothers, alongside clinical dental examinations and measurements of children’s height and weight. Importantly, the analysis also accounted for a range of other factors known to influence dental health and body weight, allowing the researchers to better isolate the impact of bottle feeding to sleep.
What the researchers found
The findings showed that bottle feeding to sleep remains common well beyond infancy and is associated with measurable health risks:
- More than 30 percent of children were still bottle fed to sleep at two years of age
- Children who were bottle fed to sleep at age two were almost twice as likely to have overweight in early childhood
- Children who were bottle fed to sleep at age three had nearly double the number of teeth affected by dental decay
Why bottle feeding to sleep matters
Lead author Heilok Cheng, a PhD candidate in the Susan Wakil School of Nursing and Midwifery at the University of Sydney, emphasised that most parents and carers are acting with good intentions but may not be fully aware of the longer term risks.
“Australian recommendations advise parents to start introducing cups at 6 months of age and stop using baby bottles at 12 months. Bottle feeding in bed is not recommended at any age. Our research now provides a much more robust evidence base for that advice.”
She explained that many commonly used drinks for toddlers can increase the risk of dental decay.
“Common toddler drinks, including cow’s milk and formula, often contain either natural or added sugars, increasing the risk of tooth decay. When a bottle is offered at bedtime it’s often being used by carers to calm an unsettled child or encourage the child to drift off to sleep. Because the bottle isn’t being offered in response to hunger, it can lead to overfeeding, putting children at risk of unhealthy weight gain.”
Cheng also highlighted the need for better support for families navigating infant and toddler feeding practices.
“We need to do more to support families and help them avoid getting into the habit of putting a child or baby to bed with a bottle, so that our future generations are set up with a healthy future from the start.”
Wider implications for policy and prevention
The authors note that the findings reinforce the importance of coordinated public health action to reduce childhood obesity and improve oral health. They also point to the potential value of universal dental care as part of a broader strategy to prevent avoidable dental disease in early life.
About the Healthy Smiles Healthy Kids study
The Healthy Smiles Healthy Kids (HSHK) cohort study is led by Associate Professor Amit Arora from Western Sydney University, in collaboration with Sydney Local Health District, South Western Sydney Local Health District, the University of Sydney, the University of Queensland, the University of Technology Sydney, and Curtin University.
The study is funded by the Australian National Health and Medical Research Council, NSW Health, the Australian Dental Research Foundation, and the Oral Health Foundation. The full paper, “Bottle feeding to sleep beyond 12 months is associated with higher risk of tooth decay and overweight in Australian children: Findings from the Healthy Smiles Healthy Kids cohort study”, was published in the Australian and New Zealand Journal of Public Health.
CCH insight:
This is an interesting study, which provides very strong evidence for avoiding bedtime bottle-feeding to help infants get to sleep. It would be interesting to know if the excess weight gain resulting from bedtime bottle-feeding is due simply to the extra calories provided by the bedtime milk, or if it also encourages increased emotional eating – it is believed that emotional eating, which is a common cause of overeating in adults, has its behavioural origin in the soothing effect we experience when suckling as a baby, so we come to associate fatty sugary food (like breast or formula milk) with bringing relief from anxiety and stress.
Read More
GLP-1 Receptor Agonists Unlikely to Meaningfully Influence Obesity-Related Cancer Risk, Review Suggests
Key Takeaways:
- Evidence from randomised trials suggests GLP-1 receptor agonists are unlikely to meaningfully increase or reduce the risk of most obesity-related cancers.
- For several cancer types, including colorectal, liver and endometrial cancer, the certainty of evidence remains low due to limited follow-up.
- Researchers emphasise the need for longer-term studies with cancer-specific outcomes to fully understand potential risks or protective effects.
A comprehensive systematic review published online on 8 December in Annals of Internal Medicine suggests that glucagon-like peptide-1 receptor agonists, commonly known as GLP-1 RAs, have little or no effect on the risk of developing cancers associated with obesity.
The review was led by Albert Ko, MD, of the Harvard T.H. Chan School of Public Health in Boston, and examined data from randomised, placebo-controlled trials involving people treated with GLP-1 RAs for type 2 diabetes or overweight and obesity. While these medications have transformed metabolic care in recent years, concerns have persisted about their long-term safety, including potential cancer risk.
Scope and purpose of the review
GLP-1 receptor agonists are widely prescribed for glycaemic control and weight management, yet their association with cancer has remained uncertain. To address this gap, the researchers conducted a systematic review and meta-analysis to assess whether treatment with GLP-1 RAs is associated with an increased or reduced risk of obesity-related cancers.
The review focused on cancers known to have strong links with excess adiposity, including thyroid, pancreatic, colorectal, gastric, oesophageal, liver, gallbladder, breast, ovarian, endometrial and kidney cancers. It also included multiple myeloma and meningioma.
Data sources and study selection
The authors searched PubMed, Embase, Web of Science, Scopus and the Cochrane Central Register of Controlled Trials from database inception through to August 2025. Only randomised, placebo-controlled trials reporting at least one of the specified cancer outcomes were eligible for inclusion.
In total, 48 trials met the inclusion criteria, encompassing 94,245 participants. None of the trials had been specifically designed to evaluate cancer outcomes, and follow-up durations were generally short.
Methods and quality assessment
Risk of bias across the included trials was assessed using the Cochrane Risk of Bias 2 tool. The certainty of evidence for each outcome was evaluated using the GRADE framework, which considers factors such as study limitations, consistency of results and precision of estimates.
Pooled odds ratios were calculated using random-effects meta-analysis to account for variation between studies.
Main findings by cancer type
The analysis found that GLP-1 receptor agonists probably have little or no effect on the risk of several common obesity-related cancers, based on evidence of moderate certainty.
Specifically:
- Thyroid cancer showed no clear association with GLP-1 RA use, with an odds ratio of 1.37 (95% CI, 0.82 to 2.31), corresponding to between one fewer and nine more cases per 10,000 people treated.
- Pancreatic cancer risk was similarly unaffected, with an odds ratio of 0.84 (95% CI, 0.53 to 1.35), equating to nine fewer to six more cases per 10,000 people.
- Breast cancer showed an odds ratio of 0.95 (95% CI, 0.60 to 1.49), indicating no meaningful difference in risk.
- Kidney cancer also demonstrated no significant association, with an odds ratio of 1.12 (95% CI, 0.78 to 1.60).
For other cancers, including colorectal, oesophageal, liver, gallbladder, ovarian and endometrial cancer, as well as multiple myeloma and meningioma, the evidence suggested little or no effect. However, the certainty of this evidence was rated as low.
For gastric cancer, the findings were described as very uncertain, reflecting sparse data and wide confidence intervals.
Consistency across analyses
The results remained consistent across multiple sensitivity and subgroup analyses. These included analyses restricted to trials with a low risk of bias, studies involving newer agents such as semaglutide or tirzepatide, and comparisons across different follow-up durations, populations, GLP-1 RA classes, doses, weight-loss profiles and durations of action.
This consistency strengthens confidence that the observed lack of association is not driven by a specific drug, dose or patient group.
Limitations of the evidence
The authors highlight important limitations that temper the conclusions. Most notably, the included trials were not designed to detect cancer outcomes and generally had relatively short follow-up periods. As a result, rare cancers or effects that emerge only after prolonged exposure may not have been captured.
Implications and next steps
Summarising the findings, the authors conclude that GLP-1 receptor agonists “may have little or no effect on risk for obesity-related cancers,” while emphasising the need for further research. As they write, “These findings offer important insights into the safety of GLP-1 RAs but highlight the need for longer-term studies with cancer-specific end points to clarify potential risks or protective effects.”
For clinicians and people considering or already using GLP-1 receptor agonists, the review provides a degree of reassurance regarding cancer risk in the short to medium term. However, ongoing surveillance and dedicated long-term studies will be essential as use of these medications continues to expand globally.
Read More
Metabolic Bariatric Surgery Shows Greater Two-Year Weight Loss Than GLP-1 RAs
Key Takeaways:
- Metabolic bariatric surgery was associated with substantially greater and more durable weight loss over two years than treatment with GLP-1 receptor agonists in adults living with class II or III obesity.
- Overall health care costs over two years were lower for people who underwent surgery, largely due to the ongoing pharmacy costs associated with GLP-1 receptor agonist therapy.
- The findings underline the importance of multidisciplinary care, particularly for clinicians managing obesity-related conditions where sustained weight reduction is central to disease control.
Overview
A large retrospective, claims-based cohort study has found that metabolic bariatric surgery delivers greater long-term weight loss benefits and lower overall health care costs over two years compared with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in adults living with severe obesity. The analysis suggests that, in real-world clinical practice, surgical approaches may offer more durable outcomes than pharmacotherapy alone for this population.
Study design and data sources
This retrospective cohort study compared outcomes following metabolic bariatric surgery with those achieved using GLP-1 receptor agonist therapy for weight management. Surgical procedures included sleeve gastrectomy and gastric bypass. Pharmacological treatments included dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, and tirzepatide.
The analysis drew on data from the Highmark Health insurance claims database linked with electronic health records from the Allegheny Health Network. In total, 30,458 adults living with class II or III obesity were included. All individuals in the weight-loss analysis had a body mass index of at least 40 at the time of enrolment.
To minimise baseline differences between groups, the researchers used propensity score weighting to balance key characteristics, including body mass index, age, sex, comorbid conditions, and patterns of health care utilisation. Adjusted analyses then compared weight-loss trajectories, obesity-related comorbidities, and total health care costs over a two-year follow-up period.
Weight loss outcomes and durability
Of the total cohort, 14,101 people underwent metabolic bariatric surgery, with a mean follow-up of 34 months. A further 16,357 people were prescribed GLP-1 receptor agonists, with a mean follow-up of 32 months.
After two years, metabolic bariatric surgery was associated with markedly greater mean total weight loss than GLP-1 receptor agonist therapy, at 28.3 per cent compared with 10.3 per cent. Weight loss following surgery was also more durable. Ninety-six per cent of people in the surgical group achieved sustained weight loss of at least 10 per cent, compared with 46 per cent of those treated with GLP-1 receptor agonists.
In addition to superior weight outcomes, people who underwent metabolic surgery experienced fewer obesity-related comorbidities and lower health care utilisation across inpatient, outpatient, and emergency care settings.
Cost analysis
Over the two-year follow-up period, metabolic bariatric surgery was associated with significantly lower mean total health care costs than GLP-1 receptor agonist therapy. Average costs were reported as $51,794 for the surgical group compared with $63,483 for those receiving GLP-1 receptor agonists.
The higher costs observed in the pharmacotherapy group were largely driven by ongoing pharmacy expenses related to long-term GLP-1 receptor agonist use. While surgery involves a higher upfront cost, the findings suggest this is offset over time by reduced medication use and lower overall health care utilisation.
Study limitations
The authors note several important limitations. Weight data were available for only a small proportion of participants, comprising 9 per cent of the surgery group and 1.6 per cent of the GLP-1 receptor agonist group. This limits the generalisability of the weight-loss findings to the full cohort.
In addition, the indication for GLP-1 receptor agonist prescriptions was not always clear, meaning some individuals may have been treated primarily for diabetes rather than obesity. However, an obesity-only subgroup analysis restricted to people without a diabetes diagnosis produced similar results, supporting the robustness of the main findings.
Follow-up duration differed slightly between groups, and adherence to GLP-1 receptor agonist therapy was likely lower in this real-world setting than would be expected in a controlled clinical trial. Finally, the cost data reflect the United States health care system and may not be directly transferable to other countries or funding models.
Clinical relevance
For clinicians managing obesity-related complications, including ophthalmologists caring for people with obesity-associated eye disease such as idiopathic intracranial hypertension, these findings highlight the broader systemic benefits of durable weight reduction. Although GLP-1 receptor agonists are increasingly recommended in the management of idiopathic intracranial hypertension, the study suggests that metabolic bariatric surgery may offer greater sustained weight loss at a lower long-term cost.
The results emphasise the value of close collaboration between ophthalmology, endocrinology, and bariatric surgery teams when supporting people whose disease burden is driven by obesity. While ongoing government discussions around medication pricing may influence future cost-effectiveness analyses, the substantial differences observed in this study indicate that metabolic surgery is likely to remain a cost-effective intervention even if GLP-1 receptor agonist costs were to decrease.
Disclosures and publication details
Financial disclosures: Dr Chantal Boisvert reports a financial relationship with Viridian Therapeutics, serving as a consultant or advisor and receiving grant support.
Read More
Maternal Obesity Linked to Early Changes in Infant Gut Microbiome, Study Suggests
Key Takeaways:
- Infants born to mothers with obesity show distinct differences in gut bacteria during the first six months of life, including reduced microbial diversity.
- These early microbial changes are associated with pathways linked to fat metabolism, particularly in the first three months after birth.
- Researchers suggest that early-life interventions targeting the gut microbiome may help reduce longer-term metabolic risks for children.
Maternal obesity and the infant gut microbiome
Babies born to mothers with obesity may begin life with a markedly different gut microbiome, a factor that could influence their metabolism and long-term health, according to new research from Nazarbayev University (NU).
The study, led by researchers Almagul Kushugulova and Samat Kozhakhmetov, explored how maternal obesity may shape the early development of the gut microbiome in infants. The research team followed 24 mothers and their babies from birth to six months of age, analysing stool samples using advanced DNA sequencing techniques.
By comparing infants born to mothers with obesity with those born to mothers without obesity, the researchers identified clear differences in the composition and diversity of gut bacteria during early life.
Reduced microbial diversity and altered metabolic pathways
The analysis showed that infants of mothers with obesity had significantly lower gut microbial diversity. In addition, these infants had a higher abundance of bacterial species associated with fat metabolism.
These differences were most pronounced during the first three months of life, a period widely recognised as critical for the establishment of the gut microbiome and for metabolic programming.
“During the first three months of life, we observed what appears to be a shift in how gut bacteria process nutrients – with a tendency toward fat storage pathways rather than breaking down carbohydrates for energy,” Kozhakhmetov explained.
He noted that this early metabolic pattern may have implications for how energy balance is regulated later in life.
Opportunities for early intervention
The researchers suggest that their findings open the door to preventive strategies during infancy. Kozhakhmetov highlighted that understanding these early microbial shifts could inform interventions aimed at promoting healthier metabolic outcomes.
This discovery, he said, “opens up possibilities for early intervention”, including approaches such as targeted probiotics or tailored dietary guidance designed to support a more balanced gut microbiome and potentially reduce future metabolic risk.
Beyond metabolism – immune and appetite regulation
The implications of the findings may extend beyond metabolism alone. The researchers propose that maternal obesity could also influence immune system development and appetite regulation in children through microbial transmission.
“We tend to think that we only pass on our genes to our children. But our research suggests that we may also pass on our bacteria – and the type of bacteria a child inherits could have important effects on their long-term health, potentially influencing their health trajectory as they grow,” Kushugulova said.
This perspective reinforces the idea that early-life exposures play a significant role in shaping health across the life course.
Placing the findings in context
The study, published in the journal Biomedicines, adds to a growing body of research highlighting the importance of the early-life microbiome. Previous studies have linked maternal weight status and gut dysbiosis to disrupted nutrient metabolism, inflammation, and changes in immune, metabolic, or neurodevelopmental outcomes in children.
As obesity during pregnancy becomes increasingly common worldwide, the authors argue that maternal health should be viewed as a key determinant not only of pregnancy outcomes, but also of a child’s longer-term metabolic health.
Implications for future research and practice
The researchers conclude that interventions targeting the gut microbiota during early infancy may represent a promising avenue for reducing health risks associated with maternal obesity. Further research will be needed to determine which strategies are most effective, when they should be implemented, and how they can be integrated into routine maternal and child healthcare.
Taken together, the findings underline the importance of addressing obesity before and during pregnancy, while also highlighting the potential of microbiome-focused approaches to support healthier outcomes for future generations.
CCH insight:
Evidence for the role of the gut microbiome in obesity and metabolic health continues to grow. This study is ground-breaking in demonstrating that maternal obesity influences the new-born child’s microbiome, potentially priming the child for health challenges later in life right from their first few weeks of life. On the positive side, this offers the potential to identify babies at risk of metabolic diseases from a very early stage of life, and also the opportunity for early interventions though diet, pre- and probiotics.
Read More
Internalised Weight Stigma Places Heavy Emotional Burden on People Seeking Bariatric Care, Indian Study Finds
Key Takeaways:
- More than 71 percent of participants preparing for metabolic and bariatric surgery reported high levels of internalised weight bias, with many expressing self-blame, shame, and reduced self-worth.
- Younger individuals and those with a higher BMI reported stronger internalised stigma, which affected emotional well-being, social relationships, and readiness to seek treatment.
- Researchers and clinicians stress that obesity is a chronic disease, not a personal failing, and warn that stigma significantly harms mental health and delays access to appropriate care.
Introduction
A new study has highlighted the profound emotional and psychological toll experienced by people living with obesity who are preparing for metabolic and bariatric surgery. The research found that internalised weight bias is widespread among individuals seeking specialist care, with many reporting depressive symptoms, reduced self-esteem, and deep feelings of self-criticism linked to their weight.
The pilot study, titled The Burden from Within—An Indian Pilot Study on Weight Bias Internalisation, was published in Obesity Surgery, the international journal of the International Federation for the Surgery and Other Therapies for Obesity (IFSO).
Weight stigma beginning in childhood and persisting into adulthood
Lead author Dr Aparna Govil Bhasker, a Mumbai-based bariatric surgeon at the MetaHeal Laparoscopy and Bariatric Surgery Centre, told The Indian Express that stigmatising experiences often begin early in life. She explained that weight-related bullying is common during childhood and continues into adulthood for many people.
“People living with obesity are frequently judged as lazy or lacking willpower. Negative media portrayals, especially weight-based memes and stigmatising content, only deepen these harmful beliefs. Post-pandemic trends show that online negativity toward obesity has grown even stronger,” she said.
Study design and participant profile
To assess the emotional impact of obesity on people seeking surgical intervention, the research team evaluated 142 participants using the validated Weight Bias Internalization Scale (WBIS). Of the total cohort, 78.9 percent were women, and all participants had a body mass index of at least 27.5 kg/m².
Researchers examined total WBIS scores, associations with age, and correlations with BMI to understand how internalised stigma manifests in individuals preparing for metabolic and bariatric surgery.
High prevalence of internalised weight bias
The study revealed striking levels of internalised stigma:
- More than 71.1 percent of participants scored above the neutral benchmark on the WBIS, indicating widespread internalisation of negative weight-based beliefs.
- Around 74.6 percent reported feeling depressed about their weight.
- More than half felt less attractive because of their weight.
- More than one-third questioned their own competence.
The findings indicate that weight stigma does not simply come from external sources. Many participants had come to believe the negative stereotypes directed at them.
Self-judgement, self-hate, and social avoidance
The report found that more than half of the individuals surveyed expressed intense self-criticism, including feelings of self-hatred related to their weight. Many participants described weight as a defining measure of their personal worth.
Social relationships were also severely affected. Approximately 45.8 percent of participants questioned why anyone they considered attractive would want to date them. Half believed they did not deserve a fulfilling social life until they lost weight.
The data also showed that younger participants experienced stronger internalised bias, while those with higher BMI levels demonstrated deeper self-directed stigma.
“This shows that obesity status and internalisation of weight bias affect social interactions, connections, and relationships, which can have a long-lasting impact on the life course of an individual’s personal, emotional, occupational, and financial trajectory,” Dr Govil Bhasker said.
Obesity rising rapidly in India but not recognised as a disease
The researchers noted that obesity rates in India have nearly doubled since 2005. Data from the fifth National Family Health Survey (2019–21) show that 24 percent of women and 22.9 percent of men aged 15 to 49 years live with overweight or obesity.
Despite this rapid rise, obesity is not officially classified as a disease in India. Dr Govil Bhasker argued that the findings underline the deep societal stigma embedded in attitudes toward obesity.
“Patients often feel ashamed, guilty, and discouraged. They endure years of negative comments, judgment, and misinformation, and over time, these negative experiences become internalized. This affects their self-worth and mental health and can delay their decision to seek proper treatment. Obesity is a chronic disease, not a personal failure, and supporting patients emotionally is just as important as helping them medically,” she said. She added that targeted interventions are urgently needed.
Stigma’s broad impact on mental and physical health
Dr Vishakha Jain, Professor of Medicine at AIIMS BibiNagar and one of the study’s co-authors, emphasised that stigma infiltrates every aspect of daily life.
She explained that persistent stigma affects physical health, mental well-being, occupational performance, and social relationships. It can contribute to unhealthy eating patterns and biological stress responses, including increased inflammation.
“Together, these pressures create a cycle of self-blame and prejudice, often making individuals feel undeserving of care,” Dr Jain said.
Conclusion
The study provides compelling evidence that internalised weight stigma is highly prevalent among people preparing for bariatric care in India and that it carries profound psychological, social, and behavioural consequences. The authors urge greater recognition of obesity as a chronic disease and call for emotional as well as medical support for individuals affected.
Read More
Manchester Launches Landmark Five-Year Mounjaro Trial to Assess Real-World Outcomes
Key Takeaways:
- A five-year real-world trial in Greater Manchester will evaluate the long-term health, employment, and quality-of-life effects of the anti-obesity medication tirzepatide.
- Up to 3,000 people will participate, with recruitment taking place through GP practices to reflect everyday clinical conditions.
- The study is part of a £279 million partnership between Eli Lilly and the UK government aimed at addressing obesity and improving population health.
Introduction: A major real-world test of tirzepatide
A five-year clinical study has begun in Greater Manchester to examine the real-world effectiveness of the anti-obesity medication tirzepatide, marketed in the United Kingdom as Mounjaro. The trial aims to understand how the treatment affects long-term health outcomes when delivered through primary care. The first participants have now been enrolled after visiting their GP, marking the formal start of the project.
Scope and scale of the trial
Up to 3,000 people are expected to take part in what is described as a first-of-its-kind real-world study. The trial forms part of a broader £279 million initiative jointly developed by US pharmaceutical company Eli Lilly and the UK government. The aim is to evaluate new ways of addressing major public health challenges, including obesity and related long-term conditions.
Professor Martin Rutter, professor of cardiometabolic medicine at the University of Manchester, emphasised the focus on early intervention. He explained that the research will assess “how effective early intervention is in tackling obesity”, and will examine a wide range of clinical and social outcomes.
What is tirzepatide?
Tirzepatide is an injectable medication that works by mimicking a hormone that helps people feel fuller for longer, thereby suppressing appetite. While marketed as Mounjaro in the UK, it is sold under the brand name Zepbound in the United States.
Clinical trials have previously shown that people receiving Mounjaro experienced up to 20 percent weight loss after 72 weeks of treatment. The Greater Manchester study will build on this evidence by measuring how the medication performs in routine practice rather than controlled trial conditions.
Real-world outcomes beyond weight
A distinctive feature of the trial is its focus on long-term and practical indicators of wellbeing. Researchers will assess health metrics but will also study broader outcomes such as employment status, sick-day absences, and quality of life. These measures are particularly relevant given the significant economic and social impact of obesity.
According to Health Secretary Wes Streeting, illnesses linked to obesity currently cost the NHS £11 billion annually. In Greater Manchester alone, approximately 600,000 adults live with obesity, said Mark Fisher, chief executive officer of the NHS Greater Manchester Integrated Care Board.
A 2023 report by Health Innovation Manchester also estimated that obesity costs the region more than £3 billion each year when NHS treatment, social care, and the impact on quality of life are taken into account.
Role of primary care in the study
The trial is major in part because it is being delivered through GP practices, providing insights into how tirzepatide performs when prescribed in everyday settings. Dr Imran Ghafoor, GP Partner at Peterloo Medical Centre in Middleton, highlighted the importance of local trust and accessibility. He stated that patients see their GP practice as a “familiar and accessible space”, adding that the research will help “test solutions tailored to real lives”.
As medications like tirzepatide move further into everyday primary care, building healthcare professionals’ understanding of how these drugs work and where they fit in treatment pathways is the focus of professional training such as the College of Contemporary Health’s GLP-1RAs in Focus, a CPD-accredited online short course.
A diverse participant group
Professor Rutter, who also serves as the trial’s chief investigator, noted that the study intends to evaluate the medication’s health effects “in a diverse group of individuals”. This emphasis on diversity aims to ensure that the findings reflect the varied experiences of people living with obesity across the region.
CCH insight
Trials like this reflect how central GLP-1 medications have become to obesity care in everyday primary care – and how much rests on the professionals delivering them understanding the science behind them. CCH’s GLP-1RAs in Focus – Why Drugs Like Ozempic Work CPD short course (2 CPD hours, fully online, CPD-accredited) gives healthcare professionals, whether or not they prescribe, a clear grounding in how drugs like tirzepatide work, where they fit in NHS treatment pathways, and how to weigh the evidence with confidence.
Explore GLP-1RAs in Focus →
Early-life Exposure to Fat-related Food Odours May Shape Lifelong Obesity Risk
Key Takeaways:
- Early exposure to fat-related food odours during development may prime the brain and body for heightened metabolic responses to high-fat foods later in life.
- Sensory cues from a maternal diet, independent of nutritional content or maternal metabolic status, can influence thermogenesis, gene expression, and susceptibility to obesity in adult mice.
- Findings suggest a previously underappreciated mechanism of metabolic programming, in which food odours encountered during gestation and lactation can affect lifelong dietary preferences and obesity risk.
Introduction
A recent study published in Nature Metabolism explores how non-nutritive sensory cues from foods rich in fat, particularly odours, influence the developing brain and metabolic pathways. The research investigates how these early sensory inputs may shape central responses to food cues, metabolic health, and the risk of obesity in adulthood. The findings expand on a substantial body of work showing that early-life nutritional exposure influences later metabolic outcomes, but highlight the specific and previously overlooked contribution of fat-related odours.
Maternal obesity and early nutritional exposure
How maternal diet affects offspring
Developmental exposure to a maternal diet high in calories and fat is a well-recognised risk factor for obesity and metabolic disorders throughout life. Numerous studies have linked maternal high-fat diet (HFD) consumption with outcomes such as excess gestational weight gain, insulin resistance, and increased adiposity in mothers, all of which may contribute to lifelong metabolic vulnerability in offspring.
Despite these strong associations, the specific components of HFDs that drive metabolic programming remain only partly understood. While nutrients themselves contribute directly to energy balance and metabolic pathways, foods also contain non-nutritive sensory elements, including volatile odours. Fetuses and newborns experience these odours during development, meaning that sensory exposure is layered on top of nutritional exposure.
Sensory memories formed early in life
Perinatal olfactory experiences contribute to the formation of sensory memories that influence food preferences and eating habits into adulthood. The authors emphasise that understanding how non-nutritive cues from a maternal HFD influence long-term dietary preferences and metabolic responses is crucial for clarifying early-life drivers of obesity risk.
Study approach
Separating nutritional and sensory influences
To distinguish nutritional caloric components from sensory components, the researchers designed an isonutritional model using a standard normal chow diet (NCD) infused with fat-related odours. This bacon-flavoured diet (BFD) enabled researchers to expose mice to fat-related sensory cues without increasing calorie content.
- BFD: NCD enriched with bacon odours, designed to mimic the odour profile of a standard lard-based high-fat diet (HFDlard).
- HFDbutter: A butter fat-based HFD used to represent a non-pork, high-fat option.
This design allowed the researchers to isolate the effect of fat-related sensory exposure during development, independent of maternal metabolic changes such as insulin resistance, weight gain, or altered lipid levels.
Odour profile analysis
A detailed chemical characterisation identified 155 volatile compounds across the diets, including aldehydes, ketones, and alcohols. Hierarchical clustering revealed:
- HFD and HFDlard shared high sensory similarity
- Both differed significantly from HFDbutter and NCD
- BFD’s odour profile closely matched HFDlard, yet its nutritional profile remained identical to NCD
These findings confirmed that BFD was an appropriate tool for studying sensory-specific metabolic programming.
Sensory cues and neural activation
Experimental analyses showed that fat-related food odours induced phosphorylation of S6 in olfactory sensory neurons (OSNs), demonstrating that the odours elicited detectable neural activation. Mice perceived BFD as more similar to HFDlard than to NCD, reinforcing that the sensory model accurately represented fat-related olfactory cues.
Early exposure and adult metabolism
Developmental exposure primes obesogenic responses
Control mice exposed only to NCD during development (NCDdev) showed no changes in interscapular brown adipose tissue (iBAT) thermogenesis or hepatic mechanistic target of rapamycin (mTOR) phosphorylation when later exposed to HFDlard odours. In contrast, mice developmentally exposed to BFD (BFDdev) displayed significant increases in both iBAT temperature and hepatic p-mTOR when encountering these odours for the first time in adulthood.
This indicates that early exposure to fat-related odours enhances metabolic responsiveness to high-fat sensory cues later in life.
Independent of maternal obesity
Importantly, these heightened responses occurred without maternal insulin resistance, adiposity, or weight gain. This demonstrates that sensory exposure alone, rather than changes in maternal metabolism, can programme obesity risk.
Sex-specific sensitivity
- Females: Lactation appeared to be the most sensitive developmental window for programming effects.
- Males: Required exposure throughout the entire developmental period to exhibit similar heightened metabolic responses.
Responses to different high-fat diets
Eight-week-old BFDdev and NCDdev mice were also exposed to HFDbutter. The aim was to test whether heightened susceptibility required precise sensory matching or whether vulnerability generalised across high-fat diets.
Findings showed that early exposure to fat-related sensory cues increased obesity susceptibility even when adult exposure involved a high-fat diet with different sensory characteristics. This suggests that early sensory programming affects broad metabolic pathways rather than specific flavour-diet associations.
While a perfect sensory match between early and later exposure was not necessary, some degree of sensory similarity still appeared relevant in shaping metabolic outcomes.
Changes in the maternal environment
The study found that feeding mothers BFD altered the volatile odour profile of both amniotic fluid and milk. These changes exposed developing offspring to fat-related sensory information during gestation and lactation, influencing their early sensory learning and shaping later responses to food.
Impairments in thermogenesis and metabolic flexibility
BFDdev mice demonstrated reduced iBAT thermogenesis compared with NCDdev controls. They also exhibited lower expression of thermogenic-related genes in iBAT, including:
- Cidea
- Pparg
These findings indicate that developmental exposure to fat-related odours impairs metabolic flexibility and weakens homeostatic responses to hypercaloric diets in adulthood.
Altered neuronal responses to fat
The researchers reported a specific impairment in Agouti-related peptide (AgRP) neuronal responsiveness to dietary fat in BFDdev mice. These neurons help regulate hunger and energy balance. Despite this, responses to major hormonal signals remained unaffected, suggesting that sensory-specific pathways were selectively disrupted.
Conclusion
The study provides compelling evidence that early-life exposure to fat-related food odours can contribute to long-term obesity risk by shaping metabolic and neuronal responses long before an individual consumes high-fat foods. These sensory cues act independently of calorie exposure and maternal metabolic health, highlighting a novel pathway through which obesity susceptibility may be programmed. Although the research was conducted in mice, it underscores the potential importance of early sensory environments in influencing metabolic health across the lifespan.
CCH insights:
This is fascinating research. We already know that the diet of a pregnant woman can influence the dietary preferences and health outcomes of her child, but now it appears odours of certain foods during pregnancy may have similar affects. It adds an intriguing new line of investigation in terms of the Developmental Origins of Health and Disease. However, we must remember this study was in mice, using bacon odours to mimic a lard-based high fat diet, so we are a long way from being able to draw conclusions about real world implications for pregnant women.
Read More