Publications

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

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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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Publication: PLoS Med

Hardeman W, Mitchell J, Pears S, Van Emmenis M, Theil F, Gc VS, et al.

6 March 2020


The majority of people do not achieve recommended levels of physical activity. There is a need for effective, scalable interventions to promote activity. Self-monitoring by pedometer is a potentially suitable strategy. We assessed the effectiveness and cost-effectiveness of a very brief (5-minute) pedometer-based intervention (‘Step It Up’) delivered as part of National Health Service (NHS) Health Checks in primary care.

The Very Brief Intervention (VBI) Trial was a two parallel-group, randomised controlled trial (RCT) with 3-month follow-up, conducted in 23 primary care practices in the East of England.

Participants were 1,007 healthy adults aged 40 to 74 years eligible for an NHS Health Check. They were randomly allocated to either intervention (505) or control group (502), stratified by primary care practice. Control participants received the NHS Health Check only. Intervention participants additionally received Step It Up: a 5-minute face-to-face discussion, written materials, pedometer, and step chart. The primary outcome was accelerometer-based physical activity volume at 3-month follow-up adjusted for sex, 5-year age group, and general practice.

Conclusions

In this large well-conducted trial, we found no evidence of effect of a plausible very brief pedometer intervention embedded in NHS Health Checks on objectively measured activity at 3-month follow-up.

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Publication: European Heart Journal

Tammy Y N Tong, Paul N Appleby, Timothy J Key, Christina C Dahm, Kim Overvad, Anja Olsen, Anne Tjønneland, Verena Katzke, Tilman Kühn, Heiner Boeing, Anna Karakatsani, Eleni Peppa, Antonia Trichopoulou, Elisabete Weiderpass, Giovanna Masala, Sara Grioni, Salvatore Panico, Rosario Tumino, Jolanda M A Boer, W M Monique Verschuren, J Ramón Quirós, Antonio Agudo, Miguel Rodríguez-Barranco, Liher Imaz, María-Dolores Chirlaque, Conchi Moreno-Iribas, Gunnar Engström, Emily Sonestedt, Marcus Lind, Julia Otten, Kay-Tee Khaw, Dagfinn Aune, Elio Riboli, Nicholas J Wareham, Fumiaki Imamura, Nita G Forouhi, Emanuele di Angelantonio, Angela M Wood, Adam S Butterworth, Aurora Perez-Cornago

24 February 2020


Summary: 

This research looked at more than 418,000 people in nine European countries who were recruited to the European Prospective Investigation into Cancer and Nutrition (EPIC) study between 1992 and 2000. Researchers found that while higher intakes of fruit, vegetables, fibre, milk, cheese or yoghurt were each linked to a lower risk of ischaemic stroke, there was no significant association with a lower risk of haemorrhagic stroke.

As the study is observational, it cannot show that the foods studied cause an increase or decrease in risk of ischaemic or haemorrhagic stroke, only that they are associated with different risks.

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Publication: Food Science & Nutrition

Rachel M. Harris, Angela M. C. Rose, Nita G. Forouhi, Nigel Unwin

5 February 2020


The Caribbean island of Barbados has a high burden of diabetes and cardiovascular disease. Dietary habits were last described in 2005. A representative population-based sample provided two nonconsecutive 24-hr dietary recalls in this cross-sectional study. Mean daily nutrient intakes were compared with the Dietary Guidelines for Americans. Subgroup differences by age, sex, and educational level were examined using logistic regression. High sugar intakes exist for both sexes with 24% consuming less than the recommended <10% of energy from added sugars. Sugar-sweetened beverages provide 43% of total sugar intake. Inadequate dietary fiber intakes exist across all age groups. Inadequate micronutrient intake was found in women for calcium, folate, thiamine, zinc, and iron. Older persons (aged 45–64 years) were more likely to report adequacy of dietary fiber and iron than younger persons (aged 25–44). Older persons (aged 45–64 years) were less likely to have an adequate supply of riboflavin (OR = 0.4, 0.2, 0.6) than younger persons. Men were more likely to have adequate intakes of iron, folate, and thiamine than women. Education was not associated with nutrient intake. The Barbadian diet is characterized by high sugar intakes and inadequate dietary fiber; a nutrient profile associated with an increased risk of obesity, type 2 diabetes, and related noncommunicable diseases.

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Publication: Nutrition Reviews

Amoutzopoulos B, Page P, Roberts C, Roe M, Cade J, Steer T et al.

30 January 2020


Overestimation or underestimation of portion size leads to measurement error during dietary assessment.

Objective

To identify portion size estimation elements (PSEEs) and evaluate their relative efficacy in relation to dietary assessment, and assess the quality of studies validating PSEEs.

Data Selection and Extraction

Electronic databases, internet sites, and cross-references of published records were searched, generating 16 801 initial records, from which 334 records were reviewed and 542 PSEEs were identified, comprising 5% 1-dimensional tools (eg, food guides), 46% 2-dimensional tools (eg, photographic atlases), and 49% 3-dimensional tools (eg, household utensils). Out of 334 studies, 21 validated a PSEE (compared PSEE to actual food amounts) and 13 compared PSEEs with other PSEEs.

Conclusion

Quality assessment showed that only a few validation studies were of high quality. According to the findings of validation and comparison studies, food image–based PSEEs were more accurate than food models and household utensils. Key factors to consider when selecting a PSEE include efficiency of the PSEE and its applicability to targeted settings and populations.

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Publication: The American Journal of Clinical Nutrition

Trichia E, Luben R, Khaw K, Wareham NJ, Imamura F, Forouhi NG

8 January 2020


Background The consumption of some types of dairy products has been associated with lower cardiometabolic disease incidence. Knowledge remains limited about habitual dairy consumption and the pathways to cardiometabolic risk.

Objective We aimed to investigate associations of habitual consumption of total and types of dairy products with markers of metabolic risk and adiposity among adults in the United Kingdom.

Methods We examined associations of changes in dairy consumption (assessed with a food-frequency questionnaire) with parallel changes in cardiometabolic markers using multiple linear regression among 15,612 adults aged 40–78 y at baseline (1993–1997) and followed up over 1998–2000 (mean ± SD: 3.7±0.7 y) in the European Prospective Investigation into Cancer and Nutrition (EPIC)–Norfolk study.

Results For adiposity, an increase in fermented dairy products [yogurt (total or low-fat) or low-fat cheese] consumption was associated with a lower increase in body weight and body mass index (BMI). For example, over 3.7 y, increasing yogurt consumption by 1 serving/d was associated with a smaller increase in body weight by 0.23 kg (95% CI: −0.46, −0.01 kg). An increase in full-fat milk, high-fat cheese, and total high-fat dairy was associated with greater increases in body weight and BMI [e.g., for high-fat dairy: β = 0.13 (0.05, 0.21) kg and 0.04 (0.01, 0.07) kg/m2, respectively]. For lipids, an increase in milk (total and low-fat) or yogurt consumption was positively associated with HDL cholesterol. An increase in total low-fat dairy was negatively associated with LDL cholesterol (−0.03 mmol/L; −0.05, −0.01 mmol/L), whereas high-fat dairy (total, butter, and high-fat cheese) consumption was positively associated [e.g., 0.04 (0.02, 0.06) mmol/L for total high-fat dairy]. For glycemia, increasing full-fat milk consumption was associated with a higher increase in glycated hemoglobin (P = 0.027).

Conclusions The habitual consumption of different dairy subtypes may differently influence cardiometabolic risk through adiposity and lipid pathways.

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Publication: Endocrine Connections

Janus C, Vistisen D, Amadid H, Witte DR, Lauritzen T, Brage S, et al.

31 December 2019


The hormone glucagon-like peptide-1 (GLP-1) decreases blood glucose and appetite. Greater physical activity (PA) is associated with lower incidence of type 2 diabetes. While acute exercise may increase glucose-induced response of GLP-1, it is unknown how habitual PA affects GLP-1 secretion. We hypothesised that habitual PA associates with greater glucose-induced GLP-1 responses in overweight individuals.

Methods

Cross-sectional analysis of habitual PA levels and GLP-1 concentrations in 1326 individuals (mean (s.d.) age 66 (7) years, BMI 27.1 (4.5) kg/m2) from the ADDITION-PRO cohort. Fasting and oral glucose-stimulated GLP-1 responses were measured using validated radioimmunoassay. PA was measured using 7-day combined accelerometry and heart rate monitoring. From this, energy expenditure (PAEE; kJ/kg/day) and fractions of time spent in activity intensities (h/day) were calculated. Cardiorespiratory fitness (CRF; mL O2/kg/min) was calculated using step tests. Age-, BMI- and insulin sensitivity-adjusted associations between PA and GLP-1, stratified by sex, were evaluated by linear regression analysis.

Results

In 703 men, fasting GLP-1 concentrations were 20% lower (95% CI: −33; −3%, P = 0.02) for every hour of moderate-intensity PA performed. Higher CRF and PAEE were associated with 1–2% lower fasting GLP-1 (P = 0.01). For every hour of moderate-intensity PA, the glucose-stimulated GLP-1 response was 16% greater at peak 30 min (1; 33%, P rAUC0-30 = 0.04) and 20% greater at full response (3; 40%, P rAUC0-120 = 0.02). No associations were found in women who performed PA 22 min/day vs 32 min/day for men.

Conclusion

Moderate-intensity PA is associated with lower fasting and greater glucose-induced GLP-1 responses in overweight men, possibly contributing to improved glucose and appetite regulation with increased habitual PA.

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Publication: The Journal of Nutrition

Jones KS, Meadows SR, Schoenmakers I, Prentice A, Moore SE

13 December 2019


Vitamin D is important to maternal, fetal, and infant health, but quality data on vitamin D status in low- and middle-income countries and response to cholecalciferol supplementation in pregnancy are sparse.

We characterized vitamin D status and vitamin D metabolite change across pregnancy and in response to cholecalciferol supplementation in rural Gambia.

This study was a secondary analysis of samples collected in a 4-arm trial of maternal nutritional supplementation [iron folic acid (FeFol); multiple micronutrients (MMN); protein energy (PE) as lipid-based supplement; PE + MMN]; MMN included 10 μg/d cholecalciferol. Plasma 25-hydroxycholecalciferol [25(OH)D3], 24,25-dihydroxycholecalciferol [24,25(OH)2D3], and C3-epimer-25-hydroxycholecalciferol [3-epi-25(OH)D3] were measured by LC-MS/MS in 863 women [aged 30 ± 7 y (mean ± SD)] in early pregnancy (presupplementation) and late pregnancy, (gestational age 14 ± 3 and 30 ± 1 wk). Changes in 25(OH)D3 and vitamin D metabolite concentrations and associations with pregnancy stage and maternal age and anthropometry were tested.

Early pregnancy 25(OH)D3 concentration was 70 ± 15 nmol/L and increased according to pregnancy stage (82 ± 18 and 87 ± 17 nmol/L in the FeFol and PE-arms) and to cholecalciferol supplementation (95 ± 19 and 90 ± 20 nmol/L in the MMN and PE + MMN-arms) (P < 0.0001). There was no difference between supplemented groups. Early pregnancy 25(OH)D3 was positively associated with maternal age and gestational age. Change in 25(OH)D3 was negatively associated with late pregnancy, but not early pregnancy, triceps skinfold thickness. The pattern of change of 24,25(OH)2D3 mirrored that of 25(OH)D3 and appeared to flatten as pregnancy progressed, whereas 3-epi-25(OH)D3 concentration increased across pregnancy.

This study provides important data on the vitamin D status of a large cohort of healthy pregnant women in rural Africa. Without supplementation, vitamin D status increased during pregnancy, demonstrating that pregnancy stage should be considered when assessing vitamin D status. Nutritionally relevant cholecalciferol supplementation further increased vitamin D status. These data are relevant to the development of fortification and supplementation policies in pregnant women in West Africa.

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Publication: International Journal of Behavioral Nutrition and Physical Activity

Lindsay T, Westgate K, Wijndaele K, Hollidge S, Kerrison N, Forouhi N, et al.

9 December 2019


Background Physical activity (PA) plays a role in the prevention of a range of diseases including obesity and cardiometabolic disorders. Large population-based descriptive studies of PA, incorporating precise measurement, are needed to understand the relative burden of insufficient PA levels and to inform the tailoring of interventions. Combined heart and movement sensing enables the study of physical activity energy expenditure (PAEE) and intensity distribution. We aimed to describe the sociodemographic correlates of PAEE and moderate-to-vigorous physical activity (MVPA) in UK adults.

Methods The Fenland study is a population-based cohort study of 12,435 adults aged 29–64 years-old in Cambridgeshire, UK. Following individual calibration (treadmill), participants wore a combined heart rate and movement sensor continuously for 6 days in free-living, from which we derived PAEE (kJ•day− 1•kg− 1) and time in MVPA (> 3 & > 4 METs) in bouts greater than 1 min and 10 min. Socio-demographic information was self-reported. Stratum-specific summary statistics and multivariable analyses were performed.

Results Women accumulated a mean (sd) 50(20) kJ•day− 1•kg− 1 of PAEE, and 83(67) and 33(39) minutes•day− 1 of 1-min bouted and 10-min bouted MVPA respectively. By contrast, men recorded 59(23) kJ•day− 1•kg− 1, 124(84) and 60(58) minutes•day− 1. Age and BMI were also important correlates of PA. Association with age was inverse in both sexes, more strongly so for PAEE than MVPA. Obese individuals accumulated less PA than their normal-weight counterparts, whether considering PAEE or allometrically-scaled PAEE (− 10 kJ•day− 1•kg− 1 or − 15 kJ•day− 1•kg-2/3 in men). Higher income and manual work were associated with higher PA; manual workers recorded 13–16 kJ•kg− 1•day− 1 more PAEE than sedentary counterparts. Overall, 86% of women and 96% of men accumulated a daily average of MVPA (> 3 METs) corresponding to 150 min per week. These values were 49 and 74% if only considering bouts > 10 min (15 and 31% for > 4 METs).

Conclusions PA varied by age, sex and BMI, and was higher in manual workers and those with higher incomes. Light physical activity was the main driver of PAEE; a component of PA that is currently not quantified as a target in UK guidelines.

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Publication: PLoS ONE

Sagelv EH, Ekelund U, Pedersen S, Brage S, Hansen BH, Johansson J, et al.

3 December 2019


Introduction Surveillance of physical activity at the population level increases the knowledge on levels and trends of physical activity, which may support public health initiatives to promote physical activity. Physical activity assessed by accelerometry is challenged by varying data processing procedures, which influences the outcome. We aimed to describe the levels and prevalence estimates of physical activity, and to examine how triaxial and uniaxial accelerometry data influences these estimates, in a large population-based cohort of Norwegian adults.

Methods This cross-sectional study included 5918 women and men aged 40–84 years who participated in the seventh wave of the Tromsø Study (2015–16). The participants wore an ActiGraph wGT3X-BT accelerometer attached to the hip for 24 hours per day over seven consecutive days. Accelerometry variables were expressed as volume (counts·minute-1 and steps·day-1) and as minutes per day in sedentary, light physical activity and moderate and vigorous physical activity (MVPA).

Results From triaxial accelerometry data, 22% (95% confidence interval (CI): 21–23%) of the participants fulfilled the current global recommendations for physical activity (≥150 minutes of MVPA per week in ≥10-minute bouts), while 70% (95% CI: 69–71%) accumulated ≥150 minutes of non-bouted MVPA per week. When analysing uniaxial data, 18% fulfilled the current recommendations (i.e. 20% difference compared with triaxial data), and 55% (95% CI: 53–56%) accumulated ≥150 minutes of non-bouted MVPA per week. We observed approximately 100 less minutes of sedentary time and 90 minutes more of light physical activity from triaxial data compared with uniaxial data (p<0.001).

Conclusion The prevalence estimates of sufficiently active adults and elderly are more than three times higher (22% vs. 70%) when comparing triaxial bouted and non-bouted MVPA. Physical activity estimates are highly dependent on accelerometry data processing criteria and on different definitions of physical activity recommendations, which may influence prevalence estimates and tracking of physical activity patterns over time.

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Publication: Diabetologia

Olov Rolandsson, Christiane S. Hampe, Nicholas J. Wareham et al

11 November 2019


Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes.

However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. The researchers investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort.

GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression.

GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors.

This study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.

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