A new study published today in Nature Medicine has identified key risk factors that increase the likelihood of individuals developing not only one but multiple non-communicable diseases, which include cardiovascular disease, cancer, chronic respiratory disease and diabetes.

The analysis of over 11,000 people found that rather than being due to chance, there are often underlying biological links in individuals with multimorbidity, which is defined as the co-occurrence of two or more long-term health conditions and is a growing public health challenge.

Multimorbidity, which affects about two thirds of people aged 65 years or over in the UK, impairs an individual’s quality of life over and above the cumulative burden from each individual disease. Understanding which diseases co-occur not at random but through common mechanisms can aid the identification of preventive strategies and lead to improvements in health care.

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An international team led by researchers at the MRC Epidemiology Unit has used a cross-platform approach across several large human studies to identify hundreds of novel genetic variants that regulate metabolite levels in the blood.

Human metabolism exchanges and converts small molecules, so called metabolites, to provide energy and essential components for each cell in the body or to excrete toxic by-products. The identification of variations in the genes that regulate these essential metabolic processes helps to better understand what causes common diseases and can lead to new strategies for their prevention and management.

In the present study published in Nature Genetics, an international team from the UK, Australia, USA, and Germany led by Dr Claudia Langenberg from the MRC Epidemiology Unit and the Berlin Institute of Health, Charité University Medicine Berlin, has identified hundreds of genetic variants not previously known to regulate blood metabolite levels in the population.

Dr Langenberg explains:

It is important to emphasize the potential clinical relevance of these findings. We see extraordinarily strong genetic effects on metabolite levels, more than three-fold compared to what we typically see for common genetic variants affecting body mass index or other complex traits, for example. We can attribute this to changes in the amino acid sequence of key metabolic ‘regulators’, such as enzymes and transporters.”

One example that demonstrates the translational potential of this work is the strong link between high levels of the amino acid serine and protection from a rare eye disease called macular telangiectasia type 2, highlighting new therapeutic opportunities. The authors showed in an independent study that the common genetic variants they identified for differences in plasma serine could distinguish between controls and patients with this severe and difficult to diagnose eye disease. In addition, the authors identify a novel mechanism by which impaired signaling through a receptor called GLP2R increases the risk of type 2 diabetes.

Dr Maik Pietzner, also at the MRC Epidemiology Unit and co-lead author of the study adds:

We hope these early, successful examples will encourage researchers and clinicians worldwide to test the relevance of our findings and the pathways we have uncovered for their disease of interest. All results are openly accessible to enable rapid follow-up via an interactive webserver www.omicscience.org.”

The team was able to achieve this largest study of this kind by being the first to integrate genetic association data for metabolites from over 85,000 individuals and demonstrating that results can successfully be combined across studies – including EPIC-Norfolk, Fenland and Interval –  which use different metabolite measurement technologies.

References

• Lotta LA, Pietzner M, Stewart ID, Wittemans LBL, Li C, et al. A cross-platform approach identifies genetic regulators of human metabolism and health. Nature Genetics, 07 January 2021. DOI: 10.1038/s41588-020-00751-5
• Omicscience open access platform:  https://omicscience.org/apps/crossplatform/

In a paper published in Diabetes Care, a research team led by scientists at the MRC Epidemiology Unit and the Department of Public Health at Aarhus University in Denmark found that replacing red and processed meat with cheese, yogurt, nuts or cereals was associated with a lower risk of type 2 diabetes.

Many dietary guidelines across the world recommend lowering consumption of red and processed meat, but if people are to eat less red and processed meat they will likely eat more of other foods. A relevant replacement could be other protein rich foods.

Daniel Ibsen, a PhD student at the Research Unit for Epidemiology in the Department of Public Health at Aarhus University and first author on the Diabetes Care paper explained:

It is important to understand that the health effect of any given food is not only determined by the food itself, but also what replaces it or what it replaces in the diet.  However, surprisingly little research evidence has been published on the link between replacing meat consumption with other specific foods and health outcomes.

This is relevant because this type of information is often neglected when having conversations about diet and health, which usually focus on eating either less or more of some foods.”

To investigate this the researchers undertook analysis of data from the EPIC-InterAct study, comparing data on 11,741 new cases of type 2 diabetes with 14,719 people who remained free of diabetes over time. The EPIC-InterAct study, led by Professor Nick Wareham of the MRC Epidemiology Unit, is the world’s largest prospective case-cohort study of incident type 2 diabetes, established across 8 European countries and nested within the pan-European EPIC study. It includes participants from the EPIC-Norfolk study. Volunteers provided extensive demographic, socio-economic and lifestyle information, as well as blood samples for genotyping and metabolic profiling.

The researchers statistically modelled the association between consuming a 1 serving (50 grams) per day lower intake of red and processed meat while consuming a 1 serving per day higher intake of other protein sources on the risk of developing type 2 diabetes. The other protein sources in the study were poultry, fish, eggs, legumes (e.g. beans, peas and lentils) (all 50 grams), cheese (30 grams), yoghurt (70 grams), milk (200 grams), cereals (mainly bread, rice and pasta) (30 grams) and nuts (10 grams).

The analysis found that replacing red and processed meat with cheese, yoghurt, nuts or cereals was associated with a lower future risk of type 2 diabetes. Although replacement with poultry, fish, eggs or milk suggested a lower risk of type 2 diabetes, there was too much uncertainty when a wide range of social factors and lifestyle behaviours of the participants were accounted for. They found no association between replacement of red and processed meat with legumes and type 2 diabetes risk.

The researchers estimated that if all participants had replaced their intake of 1 serving per day of red and processed meat with 1 serving per day of cheese, yoghurt or nuts, 8-9% of the observed new diabetes cases could have been prevented. Their estimates for cereals were suggestive of a similar impact but with greater uncertainty.

Professor Nita Forouhi, Programme leader for Nutritional Epidemiology at the MRC Epidemiology Unit and a senior author on the paper, said:

There may be a potential public health benefit for the prevention of type 2 diabetes if the dietary habits of meat-consuming European populations were shifted away from consuming red and processed meat and instead towards consuming cheese, yoghurt, nuts and, possibly, cereals.”

Aarhus University has produced a short video outlining the researcher’s findings and the public health benefits of shifting dietary habits away from consuming read meats and towards other non-meat foods.

The researchers note limitations of their research, which was based on recall of dietary habits and used data modelling techniques to study food replacement effects. However, it would be unrealistic to conduct large randomised clinical trials asking people to change and adhere to particular diets for long durations, and the study is well placed to stimulate research in other study populations to confirm the current findings and also to inform public health guidelines.

• Daniel B. Ibsen et al. Replacement of red and processed meat with other food sources of protein and the risk of type 2 diabetes in European populations; the EPIC-InterAct study. Diabetes Care (2020) 43(11):2660-2667. DOI:10.2337/dc20-1038
• Watch the Aarhus University video “Food Substitution”.

Image credit: Health-Aarhus University.

Type 2 diabetes is a chronic metabolic disease characterised by elevated levels of glucose in the blood, and presents a major and growing global public health challenge. While both genes and our environment influence the development of the disease, the underlying mechanisms are still not fully understood. The data provided by genome-wide association studies (GWAS) can help identify genetic risk factors and generate hypotheses to direct in-depth investigations that, in turn, help us better understand the biology of type 2 diabetes.

In a paper published today in Scientific Data, we describe the results from a GWAS examining  more than 8.9 million genetic variations and T2D risk among 22,326 individuals in the EPIC-InterAct study. A problem facing researchers undertaking genetic research on type 2 diabetes is that GWAS data is not publicly available for individual studies, so we decided to make the summary GWAS statistics for this study available on an open platform for researchers to use.

The EPIC-InterAct study, led by Professor Nick Wareham, is the world’s largest prospective case-cohort study of incident type 2 diabetes, established across 8 European countries and nested within the pan-European EPIC study, which includes EPIC-Norfolk study participants. Volunteers provided extensive demographic, socio-economic and lifestyle information, as well as blood samples for genotyping and metabolic profiling. During almost 4 million person-years of follow-up time among 340,234 participants, researchers identified a total of 12,403 new cases of type 2 diabetes.

In this study, we have assessed the associations of more than 8.9 million genetic variants across the genome with type 2 diabetes in 22,326 individuals of European ancestry, which includes both individuals with incident type 2 diabetes and individuals randomly selected at the start of the study to be representative of the study population as a whole. Because the  EPIC-InterAct study followed participants not yet diagnosed with type 2 diabetes over time, we were also able to examine the associations of 370 previously established type 2 diabetes genetic variants with the risk of being diagnosed with type 2 diabetes. These are the first publicly available results for such incident diabetes risk.

With the publication of this study, we aim to provide a valuable resource for the research community to conduct further genetic investigations in diabetes aetiological studies. Therefore, we have shared the full genome-wide association results in free publicly available databases, including the Dryad Data Repository and the GWAS Catalog. We hope this will encourage and facilitate future use of this resource, promote an ‘open science’ culture and cultivate wider collaborations.

• Cai L, Wheeler E, Kerrison ND, Luan J, Deloukas P et al. Genome-wide association analysis of type 2 diabetes in the EPIC-InterAct study. Sci Data (2020) 7, 393. DOI: 10.1038/s41597-020-00716-7

Sarcopenia is characterized by loss of skeletal muscle mass and function during aging and affects more than 50 million people worldwide over the age of 50 years old. Skeletal muscle is involved in voluntary movement and structural support and so a reduction in amount and strength can lead to frailty, reduced quality of life, and death. It may also cause metabolic disturbances, affecting conversion of food to energy in the body, with implications for obesity and type 2 diabetes.

Vitamin C is a nutrient found in fruits and vegetables and can help defend the cells and tissues that make up the body from potentially harmful free radical substances. Unopposed these free radicals can contribute to the destruction of muscle, thus speeding up age-related decline.

This study examined the relationship between dietary and blood vitamin C and the estimated mass of muscle in individuals within a large group of older men and women. We found people with the highest amounts of vitamin C in their diet or blood had greater estimated muscle mass, compared to those with the lowest amounts. This study suggests that dietary vitamin C is relevant for muscle health in older people and may be useful for preventing age 40 related muscle loss. [Read more…]

The majority of patients who require treatment in an acute hospital setting are older people and many have multiple chronic conditions. Known as “multimorbidity”, many studies have shown it to predict an increased rate of mortality. However, few community-based studies have considered the predictors of future hospital admissions with multimorbidity.  This study explores the relationship between this condition and potentially modifiable lifestyle factors such as smoking, obesity, physical inactivity and low plant food intake.

The study found that in people initially free of disease:

  – age and male sex predicted subsequent incident hospital admissions with multimorbidity

  – smoking, body mass index > 30, physical inactivity and a diet low in fruit and vegetables were all independently associated with the condition

Modest differences in lifestyle may have the potential to mitigate the future burden of multimorbidity in the population. [Read more…]

Lack of physical activity and exercise are known risk factors for major health conditions, including cognitive impairments such as memory and concentration problems. However, evidence as to whether physical activity actually protects against cognitive decline has often been mixed and inconclusive. This study examined the relationship between physical activity during work and leisure separately and later life cognition. Participants were from the EPIC-Norfolk study, aged 40-79 years old at baseline, from a wide range of socioeconomic backgrounds and educational attainment.

The study found:

• Individuals with no qualifications were more likely to have physically active jobs, but less likely to be physically active outside of work.
• A physically inactive job (typically a desk-job) is associated with lower risk of poor cognition, irrespective of the level of education.  Those who remained in this type of work throughout the study period were the most likely to be in the top 10% of performers.
• Those in manual work had almost three times increased risk of poor cognition than those with an inactive job

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Men and women aged 40-79 are at significantly lower (25-27%) risk of long or frequent hospital admissions if they do some form of physical activity, a new paper from the EPIC-Norfolk study suggests.

Inactive participants in the study spent just over 4 days more in hospital over the next ten years than those who did at least some physical activity, whether for work or leisure. And similar results were observed 10 years later when the same participants were 50-90 years old.

The study, by researchers at the University of Cambridge’s Department of Public Health and Primary Care and MRC Epidemiology Unit, calculates that for every inactive person who started to take at least some exercise, the NHS could save around £247 per year. This would equate to around 7% of the UK’s per capita health expenditure. [Read more…]

A Mediterranean diet is characterised by high intake of plant-based foods (fruit, vegetables, nuts and cereals) and olive oil, moderate intake of fish and alcohol and low intake of dairy products and red and processed meat.  Studies have shown that many of these dietary components of the Mediterranean diet play an important role in bone and muscle health.  We proposed that the additive effects of these individual dietary components would have a greater impact on musculoskeletal health.  The aim of the study was therefore to examine associations between adherence to a Mediterranean diet and key indicators of bone and muscle status, including fracture incidence, bone density and muscle mass. [Read more…]

Previous research has shown that physical activity is good for our bodies and minds, and spending too much time sedentary (sitting) tends to do the opposite for our health.

Physical activity is increasingly being measured using accelerometry devices, which track intensity and duration of body movement. The use of accelerometers is an advance over the previously used self-report methods, which are prone to measurement error from imprecise and biased recall, and can thereby mask the true nature and magnitude of associations.

Our study examined whether prior activity patterns were associated with later health outcomes. The large sample of detailed data on accelerometer-measured physical activity in EPIC-Norfolk, along with incident disease data and a long follow-up duration made EPIC-Norfolk an ideal study for this work. [Read more…]