Publications

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

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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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Publication: The Journal of Nutrition

Tong TYN, Koulman A, Griffin JL, Wareham NJ, Forouhi NG, Imamura F

26 October 2019


Cardiometabolic benefits of the Mediterranean diet have been recognized, but underlying mechanisms are not fully understood.

We aimed to investigate how the Mediterranean diet could influence circulating metabolites and how the metabolites could mediate the associations of the diet with cardiometabolic risk factors.

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Publication: PLoS ONE

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

25 October 2019


Compensatory behaviours may be one of the reasons for the limited success of sedentary time interventions in older adults, but this possibility remains unexplored.

Activity compensation is the idea that if we change activity levels at one time we compensate for them at a later time to maintain a set point. We aimed to assess, among adults aged ≥60 years, whether sedentary time and time spent in prolonged sedentary bouts (≥30 mins) on one day were associated with sedentary time and time spent in prolonged sedentary bouts (≥30 mins) on the following day. We also sought to determine whether these associations varied by sociodemographic and comorbid factors.

Sedentary time was assessed for seven days using hip-worn accelerometers (ActiGraph GT1M) for 3459 adults who participated in the EPIC-Norfolk Study between 2004 and 2011. We assessed day-to-day associations in total and prolonged bouts of sedentary time using multi-level regressions. We included interaction terms to determine whether associations varied by age, sex, smoking, body mass index, social class, retirement, education and comorbid factors (stroke, diabetes, myocardial infarction and cancer).

Participants (mean age = 70.3, SD = 6.8 years) accumulated 540 sedentary mins/day (SD = 80.1). On any given day, every 60 minutes spent in sedentary time was associated with 9.9 extra sedentary minutes on the following day (95% CI 9.0, 10.2). This association was greater in non-retired compared to retired participants (non-retired 2.57 extra minutes, p = 0.024) and in current compared to former and never-smokers (5.26 extra mins for current vs former; 5.52 extra mins for current vs never, p = 0.023 and 0.017, respectively). On any given day, every 60 minutes spent in prolonged bouts was associated with 7.8 extra minutes in these bouts the following day (95% CI 7.6, 8.4). This association was greater in older individuals (0.18 extra minutes/year of age, 95% CI 0.061, 0.29), and for retired versus non-retired (retired 2.74 extra minutes, 95% CI 0.21, 5.74).

Conclusion Older adults did not display day-to-day compensation. Instead, individuals demonstrate a large stable component of day-to-day time spent sedentary and in prolonged bouts with a small but important capacity for positive variation. Therefore older adults appear to be largely habitual in their sedentary behaviour. Strategies to augment these patterns may be possible, given they may differ by age, smoking, and working status.

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Publication: Journal of the American Geriatrics Society

Bielemann RM, LaCroix AZ, Bertoldi AD, Tomasi E, Demarco FF, Gonzalez MC, et al.

8 October 2019


Use of objectively measured physical activity (PA) in older adults to assess relationship between PA and risk of all-causes mortality is scarce. This study evaluated the associations of PA based on accelerometry and a questionnaire with the risk of mortality among older adults from a city in Southern Brazil.

Overall physical activity (mg), light physical activity (LPA), and moderate to vigorous physical activity (MVPA) were estimated by raw accelerometer data. The International Physical Activity Questionnaire estimated leisure time and commuting PA. Hazard ratios (excluding deaths in the first 6 mo) stratified by sex were estimated by Cox regression analysis considering adjustment for confounders.

From the 1451 older adults interviewed in 2014, 145 died (10%) after a follow-up of an average 2.6 years. Men and women in the highest tertile of overall PA had on average a 77% and 92% lower risk of mortality than their less active counterparts. The highest tertile of LPA was also related to a lower risk of mortality in individuals of both sexes. MVPA statistically reduced the risk of mortality only among women. Self-reported leisure-time PA was statistically associated with a lower risk of mortality only among men. Women in the highest tertiles of commuting PA showed a lower risk of mortality than those in the reference group.

CONCLUSION Accelerometry-based PA was associated with a lower risk of mortality among Brazilian older adults. Older individuals should practice any type of PA.

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Publication: Metabolomics

Furse S, Billing G, Snowden SG, Smith J, Goldberg G, Koulman A.

25 September 2019


This study was motivated by the report that infant development correlates with particular lipids in infant plasma.

The hypothesis was that the abundance of these candidate biomarkers is influenced by the dietary intake of the infant.

A cohort of 30 exclusively-breastfeeding mother–infant pairs from a small region of West Africa was used for this observational study. Plasma and milk from the mother and plasma from her infant were collected within 24 h, 3 months post partum. The lipid, sterol and glyceride composition was surveyed using direct infusion MS in positive and negative ion modes. Analysis employed a combination of univariate and multivariate tests.

The lipid profiles of mother and infant plasma samples are similar but distinguishable, and both are distinct from milk. Phosphatidylcholines (PC), cholesteryl esters (CEs) and cholesterol were more abundant in mothers with respect to their infants. A latent structure model showed that four lipids in infant plasma previously shown to be biomarkers clustered with cholesteryl esters in the maternal circulation.

This study found evidence that the abundance of individual lipid isoforms associated with infant development are associated with the abundance of individual molecular species in the mother’s circulation.

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Publication: European Journal of Applied Physiology

Veijalainen A, Haapala EA, Väistö J, Leppänen MH, Lintu N, Tompuri T, et al.

18 September 2019


The researchers looked at the associations of physical activity (PA), sedentary time (ST), and cardiorespiratory fitness (CRF) with heart rate variability (HRV) in children.

The participants were a population sample of 377 children aged 6–9 years (49% boys). ST, light PA (LPA), moderate PA (MPA), vigorous PA (VPA), and moderate-to-vigorous PA (MVPA), and PA energy expenditure (PAEE) were assessed using a combined heart rate and movement sensor, maximal power output per kilograms of lean body mass as a measure of CRF by maximal cycle ergometer exercise test, and HRV variables (SDNN, RMSSD, LF, and HF) using 5 min resting electrocardiography. Data were analysed by linear regression adjusted for years from peak height velocity.

In boys, ST was inversely associated and MVPA, VPA, PAEE, and CRF were directly associated with HRV variables. CRF was directly associated with all HRV variables and PAEE was directly associated with RMSSD after mutual adjustment for ST, PAEE, and CRF.

In girls, ST was inversely associated and LPA, MPA, VPA, MVPA, and PAEE were directly associated with HRV variables. After mutual adjustment for ST, PAEE, and CRF, only the inverse associations of ST with HRV variables remained statistically significant.

Higher ST and lower PA and CRF were associated with poorer cardiac autonomic nervous system function in children. Lower CRF in boys and higher ST in girls were the strongest correlates of poorer cardiac autonomic function.

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Publication: Scientific Reports

Ottaviani JI, Fong R, Kimball J, Ensunsa JL, Gray N, Vogiatzoglou A, et al.

11 September 2019


Data from dietary intervention studies suggest that intake of (−)-epicatechin mediates beneficial vascular effects in humans. However, population-based investigations are required to evaluate associations between habitual intake and health and these studies rely on accurate estimates of intake, which nutritional biomarkers can provide.

Here, we evaluate a series of structurally related (−)-epicatechin metabolites (SREM), particularly (−)-epicatechin-3′-glucuronide, (−)-epicatechin-3′-sulfate and 3′-O-methyl-(−)-epicatechin-5-sulfate (SREMB), as flavan-3-ol and (−)-epicatechin intake. SREMB in urine proved to be a specific indicator of (−)-epicatechin intake, showing also a strong correlation with the amount of (−)-epicatechin ingested (R2: 0.86 (95% CI 0.8l; 0.92).

The median recovery of (−)-epicatechin as SREMB in 24 h urine was 10% (IQR 7–13%) and we found SREMB in the majority of participants of EPIC Norfolk (83% of 24,341) with a mean concentration of 2.4 ± 3.2 µmol/L.

Our results show that SREMB are suitable as biomarker of (−)-epicatechin intake. According to evaluation criteria from IARC and the Institute of Medicine, the results obtained support use of SREMB as a recovery biomarker to estimate actual intake of (−)-epicatechin.

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