Publications

The latest list of publications from the NIHR Cambridge Biomedical Research Centre with a brief summary. 

If you are publishing research which has had funding and / or support from the NIHR Cambridge Biomedical Research Centre, please complete this form

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Publication: Clinical Biochemistry

Paquette M, Gauthier D, Chamberland A, Prat A, De Lucia Rolfe E, Rasmussen J et al.

March 2020


Summary

The objective of this study is to investigate the association between circulating PCSK9 levels and the presence of hepatic steatosis, as well as with liver biomarkers in a cohort of healthy individuals.

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Publication: Diabetes Care

Ju-Sheng Zheng, Jian’an Luan, Eleni Sofianopoulou, Fumiaki Imamura, Isobel D. Stewart, Felix R. Day, Maik Pietzner, Eleanor Wheeler, Luca A. Lotta, Thomas E. Gundersen, Pilar Amiano, Eva Ardanaz, María-Dolores Chirlaque, Guy Fagherazzi, Paul W. Franks, Rudolf Kaaks, Nasser Laouali, Francesca Romana Mancini, Peter M. Nilsson, N. Charlotte Onland-Moret, Anja Olsen, Kim Overvad, Salvatore Panico, Domenico Palli, Fulvio Ricceri, Olov Rolandsson, Annemieke M.W. Spijkerman, María-José Sánchez, Matthias B. Schulze, Núria Sala, Sabina Sieri, Anne Tjønneland, Rosario Tumino, Yvonne T. van der Schouw, Elisabete Weiderpass, Elio Riboli, John Danesh, Adam S. Butterworth, Stephen J. Sharp, Claudia Langenberg, Nita G. Forouhi, Nicholas J. Wareham

17 November 2020


Summary:

Type 2 is a condition with serious health problems. Previous research has shown higher blood levels of vitamin C were linked with lower future risk of type 2 diabetes and if this was proven, it could mean that giving vitamin C as a supplement may help in preventing the condition. Testing this theory is quite challenging due to finding the correct dose.

Researchers identified 11 genetic markers that can predict blood levels of vitamin C using a large sample of more than 50,000 adults. They tested the association of type 2 diabetes with genetically predicted vitamin C levels with a large sample size of more than 80,000 people with diabetes and up-to 840,000 people without diabetes.

They found a mismatch when comparing the link of diabetes with the genetically predicted vitamin C levels versus when used directly measured blood vitamin C levels. The researchers results for directly measured or genetically predicted blood vitamin C levels indicated that blood vitamin C is not likely to be a causal factor for the development of type diabetes. Therefore conclude that it is not justified to use vitamin C supplementation for the prevention of type 2 diabetes.

Researchers highlighted that the current research findings should be interpreted as showing no link of the micronutrient vitamin C with type 2 diabetes.

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Publication: PLoS Med

Zheng JS, Luan J, Sofianopoulou E, Sharp SJ, Day FR, Imamura F, Gundersen TE et al.

16 October 2020


Why was this study done?

There is ongoing uncertainty on whether the body’s vitamin D status indicated by blood 25-hydroxyvitamin D (25(OH)D) is relevant to the prevention of type 2 diabetes. There are conflicting findings from observational studies and a limited number of randomised controlled trials.

What did the researchers do and find?

The current research compared observational estimates of the association between 25(OH)D metabolites and incident type 2 diabetes with Mendelian randomisation estimates based on genetic instruments.

Using multiple data sources, we performed genome-wide association studies among 120,618 individuals for total 25(OH)D, and among 40,562 individuals for the other vitamin D metabolites. Among participants of European descent, 10 genetic loci were identified for total 25(OH)D, 7 loci for 25(OH)D3 and 3 loci for C3-epi-25(OH)D3.

In meta-analysis of observational studies, we found that each 1–standard deviation higher level of total 25(OH)D was associated with 20% lower risk of type 2 diabetes. The result was similar for 25(OH)D3, but for C3-epi-25(OH)D3, a positive association with type 2 diabetes was found.

With up to 80,983 type 2 diabetes cases and 842,909 controls, we assessed the association of genetically predicted differences in total 25(OH)D and its metabolites with type 2 diabetes. Neither genetically predicted higher total 25(OH)D level nor genetically predicted higher levels of 25(OH)D metabolites were significantly associated with type 2 diabetes.

What do these findings mean?

There were conflicting findings for a link with type 2 diabetes for the observational analysis of biochemically measured 25(OH)D metabolites versus the genetically predicted levels of these metabolites.

The null findings based on Mendelian randomisation analysis indicate that blood levels of 25(OH)D or its metabolites are not likely to be causal factors for the development of type 2 diabetes.

The current findings together with other evidence from randomised controlled trials do not support the use of vitamin D supplementation for the prevention of type 2 diabetes.

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Publication: Nutrients

Birdem Amoutzopoulos, Toni Steer, Caireen Roberts, David Collins, Polly Page

1 February 2020


Summary

Monitoring dietary intake of sugars in the population’s diet has great importance in evaluating the efficiency of national sugar reduction programmes. The study objective was to provide a comprehensive assessment of dietary sources of added and free sugars to assess adherence to public health recommendations in the UK population and to consider the impact of different sugar definitions on monitoring.

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Publication: Nordic Journal of Psychiatry

Josefine Freyberg , Søren Brage , Lars Vedel Kessing & Maria Faurholt-Jepsen

14 October 2020


Summary:

The subjective reporting of physical activity generally has low accuracy for quantifying energy expenditure, possibly due to problems of recall which may differ by mental health status.

This study compared the validity of self-reported physical activity (using International Physical Activity Questionnaire, IPAQ) in patients with bipolar disorder, unaffected relatives and healthy controls using combined heart rate and movement sensing as the objective criterion measure.

Correlations were positive but weak between IPAQ and sensor-based estimates for all groups combined, indicating IPAQ may be used to approximately rank individuals by activity level but there was no clear evidence that validity was any different in the bipolar patients as validity in the two comparison groups was higher (unaffected relatives) and lower (healthy controls).

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Publication: BMJ

Deschasaux, M, Huybrechts, I, Julia, C, Hercberg, S, Egnell, M, Srour, B, et al.

16 September 2020


This study looked to see if the Food Standards Agency nutrient profiling system (FSAm-NPS), which grades the nutritional quality of food products and is used to derive the Nutri-Score front-of-packet label to guide consumers towards healthier food choices, is associated with mortality, using the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from 23 centres in 10 European countries.

More than 500,ooo participants’ dietary questionnaires were analysed to assess their usual dietary intakes. A FSAm-NPS score was calculated for each food item per 100 g content of energy, sugars, saturated fatty acids, sodium, fibre, and protein, and of fruit, vegetables, legumes, and nuts. An overall mean of all foods consumed was also calculated; the higher the score the lower the overall nutritional quality of the diet.

The results showed that consuming foods with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher mortality for all causes and for cancer and diseases of the circulatory, respiratory, and digestive systems, supporting the relevance of FSAm-NPS to characterise healthier food choices in the context of public health policies (eg, the Nutri-Score) for European populations. This is important considering ongoing discussions about the potential implementation of a unique nutrition labelling system at the European Union level.

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Publication: Aging

Yerrakalva D, Hajna S, Wijndaele K, Westgate K, Khaw K, Wareham N et al.

12 September 2020


Development of effective strategies to reduce sedentary time among older adults necessitates understanding of its determinants but longitudinal studies of this utilising objective measures are scarce.

Among 1536 older adults (≥60 years) in the EPIC-Norfolk study, sedentary time was assessed for seven days at two time-points using accelerometers. We assessed associations of change in total and prolonged bouts of sedentary time (≥ 30 minutes) with change in demographic and behavioural factors using multi-level regression.

Over follow-up (5.3±1.9 years), greater increases in total sedentary time were associated with older age, being male, higher rate of increase in BMI, lower rate of increase in gardening (0.5 min/day/yr greater sedentary time per hour/week/yr less gardening, 95% CI 0.1, 1.0), a lower rate of increase in walking (0.2 min/day/yr greater sedentary time per hour/week/yr less walking, 95% CI 0.1, 0.3) and a higher rate of increase in television viewing. Correlates of change in prolonged sedentary bouts were similar.

Conclusion: Individuals in specific sub-groups (older, male, higher BMI) and who differentially participate in certain behaviours (less gardening, less walking and more television viewing) but not others increase their sedentary time at a higher rate than others; utilising this information could inform successful intervention content and targeting.

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Publication: European Journal of Preventive Cardiology

Sangeeta Lachman, S Matthijs Boekholdt, Robert N Luben, Stephen J Sharp, Soren Brage, Kay-Tee Khaw, Ron JG Peters, Nicholas J Wareham

29 August 2020


Summary

There is broad consensus that regular physical activity yields major health benefits. However, current guidelines on physical activity are mainly aimed at middle-aged adults. It is unclear whether physical activity also translates into cardiovascular health benefits in older adults.

Researchers analysed data from the EPIC Norfolk prospective population study. Cox proportional hazards models were used to analyse the association between physical activity levels and time to CVD events in three age categories (<55, 55–65 and >65 years). Interaction between age categories and physical activity levels was assessed.

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Publication: Nature Medicine

Strain, T., Wijndaele, K., Dempsey, P., Sharp, S., Pearce, M., Jeon, J., Lindsay, T., Wareham, N. and Brage, S.

17 August 2020


Use of wearable devices that monitor physical activity is projected to increase more than fivefold per half-decade. In this study the researchers investigated how device-based physical activity energy expenditure (PAEE) and different intensity profiles were associated with all-cause mortality.

96,476 UK Biobank participants (mean age 62 years, 56% female) were studied and followed up for 3.1 years. The research showed that higher PAEE was associated with a lower hazard of all-cause mortality for a constant fraction of moderate-to-vigorous-intensity physical activity (MVPA).

The results show that higher volumes of PAEE are associated with reduced mortality rates, and achieving the same volume through higher-intensity activity is associated with greater reductions than through lower-intensity activity. The linkage of device-measured activity to energy expenditure creates a framework for using wearables for personalized prevention.

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Publication: Cell Metabolism

Marenne, G., Hendricks, A., Perdikari, A., Bounds, R., Payne, F., Keogh, J., Lelliott, C., Henning, E., Pathan, S., Ashford, S., Bochukova, E., Mistry, V., Daly, A., Hayward, C., Wareham, N., O’Rahilly, S., Langenberg, C., Wheeler, E., Zeggini, E., Farooqi, I. and Barroso, I.

2 June 2020


Obesity is genetically heterogeneous with monogenic and complex polygenic forms. Using exome and targeted sequencing in 2,737 severely obese cases and 6,704 controls, the researchers identified three genes (PHIPDGKI, and ZMYM4) with an excess burden of very rare predicted deleterious variants in cases.

In cells, they showed that PHIP is involved in human energy homeostasis, which has potential diagnostic and therapeutic implications for patients with obesity and developmental delay.

Additionally, they found an excess burden of predicted deleterious variants involving genes nearest to loci from obesity genome-wide association studies.

Genes and gene sets influencing obesity with variable penetrance provide compelling evidence for a continuum of causality in the genetic architecture of obesity, and explain some of its missing heritability.

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Publication: Nutrients

Silvia Pastorino, Tom Bishop, Stephen J. Sharp, Matthew Pearce, Tasnime Akbaraly, Natalia B. Barbieri, Maira Bes-Rastrollo, Joline W. J. Beulens, Zhengming Chen, Huaidong Du, Bruce B. Duncan, Atsushi Goto, Tommi Härkänen, Maryam Hashemian, Daan Kromhout, Ritva Järvinen, Mika Kivimaki, Paul Knekt, Xu Lin, Eiliv Lund, Dianna J. Magliano, Reza Malekzadeh, Miguel Ángel Martínez-González, Gráinne O’Donoghue, Donal O’Gorman, Hossein Poustchi, Charlotta Rylander, Norie Sawada, Jonathan E. Shaw, Maria Schmidt, Sabita S. Soedamah-Muthu, Liang Sun, Wanqing Wen, Alicja Wolk, Xiao-Ou Shu, Wei Zheng, Nicholas J. Wareham, and Nita G. Forouhi

7 April 2020


Summary

Eating fish is generally considered part of a healthy diet. This is based on previous evidence from research that found benefits of consuming fish for heart disease. That is why there are various dietary guidelines that recommend that people should consume fish regularly.

Whether fish consumption also has a role in the prevention of type 2 diabetes is not clear. In previous research it was reported that the relationship between eating fish and developing type 2 diabetes may vary in different parts of the world.

To understand this better, we undertook research including data from studies in several world regions.  The InterConnect project enabled us to analyse data from nearly one million people from 28 studies across the world, among whom 48,000 people developed type 2 diabetes over time. Researchers analysed data on different types of fish, including shellfish, fatty fish, lean fish and fried fish.

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Publication: International Journal of Epidemiology

Brage S, Lindsay T, Venables M, Wijndaele K, Westgate K, Collins D, et al.

19 March 2020


This is the first nationally representative study of human energy expenditure, covering the UK in the period 2008-2015.

Key messages:

  • Total energy expenditure (MJ/day) increases steadily with age throughout childhood and adolescence, peaks in the 3rd decade of life in women and 4th decade of life in men, before decreasing gradually in old age.
  • Physical activity energy expenditure (kJ/day/kg or kJ/day/kg fat-free mass) declines steadily with age from childhood to old age, more steeply so in males.
  • Body-fat percentage is strongly inversely associated with physical activity energy expenditure.
  • We found little evidence that energy expenditure varied by geographical region, over time, or by dietary macronutrient composition.
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