MRC Epidemiology Unit
The latest news from the MRC Epidemiology Unit
Welcome to the summer 2023 issue of epigram, our quarterly newsletter.
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In this issue: the latest on diet and diabetes, new genetic insights, finding out what makes us tick as well as the latest events, publications and opportunities at the Unit.
Diet and diabetes – seeing new connections
Biomarkers help us see health benefits of Mediterranean diet
Research suggests that people following a Mediterranean diet have a lower risk of type 2 diabetes. However, that link has been uncertain because of the subjectivity of self-reported diets. So Unit PhD student Jakub Sobiecki and colleagues have developed a new blood test that can give an objective biological indicator of adherence to the diet.
No one biomarker can predict the Mediterranean diet, so researchers examined multiple biomarkers that reflect an individual’s diet, for example the levels of particular vitamins or fatty acids circulating in the blood. They derived a composite score by analysing these biomarkers in blood samples from an Australian trial where participants were assigned at random to follow either their usual diet or the Mediterranean diet for 6 months.
The researchers then applied their composite biomarker score to the EPIC study, which included over 9,000 Europeans who developed type 2 diabetes, as well as a control group. They found that those whose biomarker score indicated greater adherence to a Mediterranean diet were less likely to develop type 2 diabetes.
Not only that, but using the biomarker score identified a stronger link between the Mediterranean diet and reduced risk of type 2 diabetes than study participants’ self-reported diets, suggesting that past self-report-based studies may have under-estimated the health benefits of a Mediterranean diet. Read more.
Tackling diabetes – insights from our genes
Unit scientists are harnessing the power of innovative genomic research in large study cohorts and finding new insights into the origins, prevention and treatment of type 2 diabetes.
DNA discovery shows how we keep a healthy blood sugar level after meals
A study of the DNA of more than 55,000 people worldwide has shed light on how we maintain healthy blood sugar levels after we have eaten, with implications for our understanding of how the process goes wrong in type 2 diabetes.
Insulin resistance in muscle and fat tissue after eating may be key to development of type 2 diabetes, but most genetic studies of insulin resistance have focused on the fasting state when insulin is largely acting on the liver. Unit PhD student Dr Alice Williamson was part of an international team which used genetic data from non-diabetic participants in 28 studies to look for key genetic variants that influenced insulin levels measured two hours after a sugary drink.
Their work highlighted the importance of a variant in the gene for GLUT4, the critical protein responsible for taking up glucose from the blood into cells after eating, as well as another 14 genes that influence how GLUT 4 acts and is used in the body.
Problems regulating blood glucose after a meal can be an early sign of increased type 2 diabetes risk, so the researchers are hopeful that the discovery of the mechanisms involved can aid the development to new treatments. Read more.
Can improving fitness help prevent type 2 diabetes? Genetics may hold the answer
Higher cardiorespiratory fitness is associated with higher insulin sensitivity and lower risk of type 2 diabetes, but until now it hasn’t been clear if the relationship is causal. As a result cardiorespiratory fitness is rarely measured in people at risk of developing type 2 diabetes.
Unit scientists have now provided strong evidence that higher fitness is linked through our genes with a lower risk of type 2 diabetes, independent of body fat.
The researchers first developed a genetic risk score for fitness that included as many genes associated with fitness as possible. They made use of the fact that a lower resting heart rate is strongly correlated with higher fitness, and resting heart rate had been measured in most UK Biobank participants, given them data on 450,000 participants and 160 gene variants.
This genetic risk score was then used in a genetic approach known as Mendelian Randomization, using in data from more than 55,000 people with type 2 diabetes and more than 400,000 controls in the DIAMANTE consortium. This revealed that higher genetically predicted fitness is associated with lower risk of type 2 diabetes, independent of body fat mass. In a follow-up analysis in more than 10,000 Fenland Study participants they identified several proteins as potential mediators of this relationship.
Based on these findings they say that improving fitness should be evaluated in future clinical trials as a way to prevent and manage type 2 diabetes. Read more.
Why our biological clocks tick at different speeds
Large population-based studies are providing researchers with opportunities to better understand how our bodies change as we age, and to use this knowledge to support healthy aging.
Challenging current thinking on genetic causes of very early menopause
The genetic causes of very early menopause will have to be reconsidered after researchers found that nearly all women who carried variations thought to cause the condition in fact had their menopause at an older age.
Variants in any one of more than 100 genes were thought to cause premature ovarian insufficiency (POI). Under current guidance a variation in one of these genes is cause for clinicians to consider a genetic diagnosis of POI. The new results from the largest genetic study of premature menopause to date indicate this needs to be reconsidered, because premature menopause is caused by a combination of variants in many genes, and non-genetic factors.
The researchers did identify several genetic variants that had a subtle impact on reproductive longevity. For example, women carrying two genetic particular variants experienced menopause up to three years earlier than the general population.
These findings are from an analysis of UK Biobank genetic data led by scientists at the MRC Epidemiology Unit and University of Exeter. Researchers are continuing to use human genomics research to better understand the biology of reproductive aging. Read more.
EPIC-Norfolk Open Science advances understanding of biology of aging
The MRC Epidemiology Unit is committed to Open Science to make our research more accessible, equitable, transparent and reproducible. A recent Science Magazine paper is a good example of how our Open Science platforms can support innovative research in practice.
Researchers at Columbia University have reported that animal studies indicate that supplementation of the diet with taurine – an amino acid used in many energy drinks – may slow the aging process. But do their findings in animals apply to humans? One important question they asked was if there was any evidence that circulating taurine levels in humans are associated with age-related health conditions.
The researchers were able to analyse data on circulating levels of taurine and its metabolites as well as clinical risk factors associated with aging in almost 12,000 participants from the MRC Epidemiology Unit-run EPIC-Norfolk Study.
The process of obtaining permission to access and analyse data from human research studies is usually time consuming for all parties involved, because of the need to ensure that the privacy and personal data of study participants is protected. However, rather than having to seek permission to access EPIC-Norfolk data, the Columbia researchers were able to download summary, anonymized, statistics from the Omicscience webserver omniscience.com. This allowed them to quickly analyse profiles of circulating metabolites, and the links between them and markers of aging.
They found that higher levels of circulating taurine and its metabolites were indeed associated with lower biological markers of aging, results that were consistent with taurine deficiency contributing to aging in humans. Interestingly, their research also suggests that exercise training is associated with an increase in blood taurine concentrations, potentially helping to explain the anti-aging effects of physical activity. Read more.
Researcher voices
Air pollution is a hidden pandemic in Africa – tips on how to reduce your exposure and help combat it
Air Pollution is worsening in African cities, with consequences for economies & health. In an article for The Conversation, Unit scientist Dr Meelan Thondoo joins Dr Gabriel Okello in a discussion of strategies that individuals, communities and policy makers can adopt to reduce the threat. Read more.
What does the World Health Organization’s new guidance on non-sugar sweeteners mean for you?
The World Health Organization (WHO) recently released new guidance on the use of non-sugar sweeteners, recommending that they should “not be used as a means of achieving weight control or reducing the risk of noncommunicable diseases”. In a commentary published on our website, Unit PhD student Lorenzo Del Grosso examines the evidence on which the new guidance is based and what it means for consumers. Read more.
Our latest publications
You can now find all publications from the MRC Epidemiology Unit at our new Publications Database: https://publications.mrc-epid.cam.ac.uk/ You can search by journal, year, study, programme, Unit author, and keywords in the title and abstract. Since the last issue of epigram, we have published the following papers:
- Lifestyle Score and Risk of Hypertension in the Airwave Health Monitoring Study of British Police Force Employees Aljuraiban GS et al. Int J Environ Res Public Health.
- Do socioeconomic inequities arise during school-based physical activity interventions? An exploratory case study of the GoActive trial Alliott O et al. BMJ Open.
- Reducing Sitting Time in Type 1 Diabetes: Considerations and Implications Alobaid AM et al. Can J Diabetes.
- Characterisation of dominant-negative GH receptor variants reveals a potential therapeutic target for short stature Andrews A et al. Eur J Endocrinol.
- Susceptibility to Reinfection with SARS-CoV-2 Virus Relative to Existing Antibody Concentrations and T cell Response Atef S et al. Int J Infect Dis.
- Are there inequalities in the attendance and effectiveness of behavioural weight management interventions for adults in the UK? Protocol for an individual participant data (IPD) meta-analysis Birch J et al. BMJ Open.
- Loci for insulin processing and secretion provide insight into type 2 diabetes risk Broadaway KA et al. Am J Hum Genet.
- Association between classes and subclasses of polyphenol intake and 5-year body weight changes in the EPIC-PANACEA study Castañeda J et al. Obesity (Silver Spring).
- Early development of infant gut microbiota in relation to breastfeeding and human milk oligosaccharides Chichlowski M et al. Front Nutr.
- A longitudinal study of lifestyle behaviours in emerging adulthood and risk for symptoms of depression, anxiety, and stress Collins S et al. J Affect Disord.
- Content analysis of on-package formula labelling in Great Britain: use of marketing messages on first infant, follow-on, growing-up and specialist formula Conway R et al. Public Health Nutr.
- Identifying priority interventions using the Behaviour Change Wheel to improve public primary school food environments in urban South Africa Erzse A et al. Lancet Glob Health.
- Embracing complexity: making sense of diet, nutrition, obesity and type 2 diabetes Forouhi NG. Diabetalogia.
- Time spent on social media use and BMI z-score: a cross-sectional explanatory pathway analysis of 10,798 14-year-old boys and girls Foubister C et al. Pediatr Obes.
- Screen time, social media use, and weight-change behaviors: Results from an international sample Ganson KT et al. Prev Med.
- Non-occupational physical activity and risk of cardiovascular disease, cancer, and mortality outcomes: a dose-response meta-analysis of large prospective studies Garcia L et al. Br J Sport Med.
- Cross-Lagged Associations between Physical Activity, Motor Performance, and Academic Skills in Primary-School Children Haapala EA et al. Med Sci Sports Exerc.
- Politics and Fantasy in UK Alcohol Policy: A Critical Logics Approach Hawkins B et al. Critical Policy Studies.
- The moderating role of eating behaviour traits in the association between exposure to hot food takeaway outlets and body fatness Hoenink J et al. Int J Obes.
- Cooling cities through urban green infrastructure: a health impact assessment of European cities Iungman T et al. Lancet.
- Bayesian multistate modelling of incomplete chronic disease burden data Jackson C et al. J R Stat Soc Ser A Stat Soc.
- Eating disorder risk during behavioral weight management in adults with overweight or obesity: A systematic review with meta-analysis Jebeile H et al. Obesity Rev.
- Identifying Factors Which Influence Eating Disorder Risk during Behavioral Weight Management: A Consensus Study Jebeile H et al. Nutrients.
- Protocol and application of basal erythrocyte transketolase activity to improve assessment of thiamine status Jones K et al. Ann N Y Acad Sci.
- Recruitment and retention into longitudinal health research from an adolescent perspective: a qualitative study Jong ST et al. BMC Med Res Method.
- Association Between Self-Reported Polycystic Ovary Syndrome with Chronic Diseases Among Emiratis: A Cross-Sectional Analysis from the UAE Healthy Future Study Juber NF et al. Int J Womens Health.
- Multilevel correlates of abdominal obesity in adolescents and youth living with HIV in peri-urban Cape Town, South Africa Kamkuemah M et al. PLoS One.
- Changes in online food access during the COVID-19 pandemic and associations with deprivation: a longitudinal analysis Keeble M et al. JMIR Public Health Surveil.
- Large scale phenotype imputation and in vivo functional validation implicate ADAMTS14 as an adiposity gene Kentistou KA et al. Nat Commun.
- Urban policy interventions to reduce traffic-related emissions and air pollution: A systematic evidence map Khreis H et al. Environ Int.
- Proteogenomic links to human metabolic diseases Koprulu M et al. Nat Metab.
- Distribution and association of interpregnancy weight change with subsequent pregnancy outcomes in Asian women Ku CW et al. Sci Rep.
- Eating Disorders In weight-related Therapy (EDIT) Collaboration: Rationale and study design Lister NB et al. Nutr Res Rev.
- The Opioid Industry Document Archive: New Directions in Research on Corporate Political Strategy MacKenzie R et al. Int J Drug Policy.
- Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus Mathieson I et al. Nat Hum Behav.
- The association between plasma zinc concentrations and markers of glucose metabolism in adults in Cameroon Mba CM et al. Br J Nutr.
- The need for future research into the assessment and monitoring of eating disorder risk in the context of obesity treatment McMaster CM et al. Int J Eat Disord.
- Butyrate in human milk: associations with milk microbiota, milk intake volume, and infant growth Olga L et al. Nutrients.
- Worldwide Associations of Fruit and Vegetable Supply with Blood Pressure from 1975 to 2015: An Ecological Study Oude Griep L et al. BMJ Nutr Prev Health.
- Reactions of industry and associated organisations to the announcement of the UK Soft Drinks Industry Levy: longitudinal thematic analysis of UK media articles, 2016-18 Penney TL et al. BMC Public Health.
- Association Between Change in Physical Activity During Pregnancy and Infant Birth Weight Peter-Marske KM et al. Matern Child Health J.
- Associations between trajectories of obesity prevalence in English primary school children and the UK soft drinks industry levy: an interrupted time series analysis of surveillance data Rogers NT et al. PLoS Med.
- Incomplete reporting of complex interventions: a call to action for journal editors to review their submission guidelines Ryan M et al. Trials.
- Mediterranean diet adherence is associated with lower dementia risk, independent of genetic predisposition: findings from the UK Biobank prospective cohort study Shannon OM et al. BMC Med.
- Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk Shrine N et al. Nat Genet.
- Quantifying the relationship between physical activity energy expenditure and incident Type 2 Diabetes: a prospective cohort study of device-measured activity in 90,096 adults Strain T et al. Diabetes Care.
- Cardiorespiratory Optimisation By Arteriovenous fistula Ligation after renal Transplantation (COBALT): study protocol for a multicentre randomised interventional feasibility trial Surendrakumar V et al. BMJ Open.
- Denormalising alcohol industry activities in schools van Schalkwyk MC et al. Lancet Public Health.
- Centile reference chart for resting metabolic rate through the life course Watson L et al. Arch Dis Child.
- Socioeconomic inequalities in food purchasing practices and expenditure patterns: Results from a cross-sectional household survey in western Kenya Were V et al. Front. Public Health.
- Shorter sleep among adolescents is associated with lower fruit and vegetable consumption the following day Winpenny E et al. Int J Behav Nutr Phys Act.
- Genome-wide genotype-serum proteome mapping provides insights into the cross-ancestry differences in cardiometabolic disease susceptibility Xu F et al. Nat Commun.
- An atlas of genetic scores to predict multi-omic traits Xu Y et al. Nature.
- Dietary fatty acids and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition Yammine SG et al. BMC Cancer.
- Ethnic disparities in COVID-19 outcomes: a multinational cohort study of 20 million individuals from England and Canada Zaccardi F et al. BMC Public Health.
- Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation study Zhao J et al. EBioMedicine.
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