Publications by authors named "Stephen J Sharp"

197 Publications

Is occupational physical activity associated with mortality in UK Biobank?

Int J Behav Nutr Phys Act 2021 07 27;18(1):102. Epub 2021 Jul 27.

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Level 3 Institute of Metabolic Science, Addenbrooke's Treatment Centre, Cambridge Biomedical Campus, Cambridge, CB2 0SL, UK.

Background: Current physical activity guidelines do not distinguish between activity accumulated in different behavioural domains but some studies suggest that occupational physical activity (OPA) may not confer health benefits and could even be detrimental. The purpose of this study was to investigate associations between OPA and mortality outcomes.

Methods: From baseline (2006-2010), 460,901 UK Biobank participants (aged 40-69 years) were followed for a median 12.0 (IQR: 11.3-12.7) years. OPA was categorised by cross-tabulating degree of manual work and walking/standing work amongst those in paid employment (n = 267,765), and combined with categories of occupational status for those not in paid employment (n = 193,136). Cox proportional hazards models were used to estimate sex-stratified hazard ratios (HR) and 95% confidence intervals (CI) for mortality from all causes, CVD, and cancer by occupational group, and for working hours/week and non-occupational physical activity stratified by occupational group. Models included adjustment for age and a range of lifestyle, socio-economic and health-related covariates.

Results: During 5,449,989 person-years of follow-up, 28,740 deaths occurred. Compared to those reporting no heavy manual or walking/standing work (e.g. sedentary office workers) and adjusting for covariates, retirement was associated with lower mortality in women (HR = 0.62, CI: 0.53-0.72) and men (HR = 0.80, CI: 0.71-0.90), whereas unemployment was associated with higher mortality in men only (HR = 1.24, CI: 1.07-1.45). Within the working population, there was no evidence of differences in all-cause, CVD or cancer mortality by OPA group when comparing those reporting higher levels of OPA to the lowest OPA reference group for both women and men. Working < 35 h/week versus 35-40 h/week was associated with lower mortality in women (HR = 0.85, CI: 0.79-0.92) and men (HR = 0.83, CI: 0.78-0.89), with no interaction by OPA. Non-occupational physical activity was associated with lower mortality in working women (HR = 0.89 per 5 kJ/day/kg, CI: 0.84-0.95) and men (HR = 0.87 per 5 kJ/day/kg, CI: 0.84-0.91), with no interaction by OPA group.

Conclusions: Jobs classified as higher levels of OPA may not be as active as reported, or the types of physical activity performed in those jobs are not health-enhancing. Irrespective of OPA category or employment status, non-occupational physical activity appears to provide health benefits.
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http://dx.doi.org/10.1186/s12966-021-01154-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314512PMC
July 2021

Impact of achievement and change in achievement of lifestyle recommendations in middle-age on risk of the most common potentially preventable cancers.

Prev Med 2021 Jul 7;153:106712. Epub 2021 Jul 7.

The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge School of Clinical Medicine, Box 113 Cambridge Biomedical Campus, Cambridge CB2 0SR, UK; MRC Epidemiology Unit, University of Cambridge, Institute of Metabolic Science, Cambridge CB2 0QQ, UK. Electronic address:

This study aimed to assess the association between achievement, and within-person change in achievement, of lifestyle recommendations in middle-age and incidence of the most common potentially preventable cancers. We used data from 44,572 participants from the Swedish Västerbotten Intervention Programme who had attended at least two health checks 9-11 years apart. We assessed the association between the mean number of healthy lifestyle recommendations achieved (lifestyle score), and change in lifestyle score between the health checks, and risk of one or more of the eight most common potentially preventable cancers using Cox regression. Participants were followed-up for 11.0 (SD 4.9) years. A higher mean lifestyle score was associated with a lower hazard of cancer in men (HR 0.81 (95%CI 0.74-0.90) per unit increase) and women (HR 0.90 (0.84-0.96)). There was no evidence of a linear association between change in lifestyle score and risk (HR 0.93 (0.85-1.03) and HR 1.004 (0.94-1.07) per unit change for men and women respectively). When comparing those with an increase in lifestyle score of ≥2 with those who improved less or declined in achievement the HR was 0.74 (0.54-1.00) and 1.02 (0.84-1.24) for men and women respectively. These findings support the inclusion of lifestyle recommendations in cancer prevention guidelines. They further suggest that interventions to change health behaviours in middle-age may reduce risk of the most common preventable cancers in men, but this association was not observed in women. Strategies to encourage healthy lifestyles earlier in the life course may be more effective.
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http://dx.doi.org/10.1016/j.ypmed.2021.106712DOI Listing
July 2021

Longitudinal associations between prepubertal childhood total energy and macronutrient intakes and subsequent puberty timing in UK boys and girls.

Eur J Nutr 2021 Jul 7. Epub 2021 Jul 7.

MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus Box 285, Cambridge, CB2 0QQ, UK.

Purpose: Early puberty is associated with adverse health outcomes. To identify potential modifiable factors for puberty timing, we examined the associations of prepubertal childhood macronutrient intakes with puberty timing in boys and girls.

Methods: In the Avon Longitudinal Study of Parents and Children, macronutrient intakes at age 6 years were predicted using random intercepts linear regression models of dietary data at 3, 4, 7 (assessed by food frequency questionnaires) and 7.5 years (by 3-day food diaries). Timings of puberty onset (Tanner stage 2 genital or breast (B2) development) and puberty completion (voice breaking (VB) or menarche) were calculated from annual parental and child reports at 8-17 years. Age at peak height velocity (PHV) was derived from repeated height measurements at 5-20 years. Linear regression models were fit to estimate the associations of total energy (TEI) and macronutrient intakes (carbohydrate, fat, protein) with puberty timing traits, adjusting for maternal and infant characteristics.

Results: Among 3811 boys, higher TEI, but no macronutrient, was associated with earlier VB. Among 3919 girls, higher TEI was associated with earlier ages at B2, PHV, and menarche. Higher protein intake but not carbohydrate or fat intake (in energy partition models) and substitution of dietary protein for carbohydrate (in nutrient density and residual models) was associated with earlier B2, PHV, and menarche in girls. Findings were not attenuated on additional adjustment for body fat percentage during adolescence.

Conclusions: These findings suggest habitual total energy intakes in children, and protein intakes in girls, as potential modifiable determinants of puberty timing.
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http://dx.doi.org/10.1007/s00394-021-02629-6DOI Listing
July 2021

Genetic Risk, Muscle Strength, and Incident Stroke: Findings From the UK Biobank Study.

Mayo Clin Proc 2021 07;96(7):1746-1757

Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City.

Objective: To examine the associations of muscle strength and genetic risk for stroke with stroke incidence.

Participants And Methods: We included 284,767 white British participants of UK Biobank without genetic relatedness and stroke or myocardial infarction at baseline between March 13, 2006, and October 1, 2010. Genetic risk was assessed with polygenic risk scores, calculated by summing the risk-increasing alleles, weighted by the effect estimates. Muscle strength was assessed through grip strength tests by hand dynamometers. Incidence of overall (n= 4008), ischemic (n= 3031), and hemorrhagic (n=1073) stroke was adjudicated during 11.5-year follow-up.

Results: Compared with the bottom muscle strength tertile, hazard ratios (95% CI) of stroke were 0.81 (0.75 to 0.87) and 0.76 (0.71 to 0.82) for the middle and top muscle strength tertiles, respectively, after adjustment for confounders and genetic risk; higher genetic risk was independently associated with higher stroke incidence. Stroke hazards for the top muscle strength tertile were consistently lower across genetic risk strata, with no evidence of interaction. Compared with individuals with high muscle strength and low genetic risk, stroke hazards were higher for individuals who had medium or high genetic risk combined with low or medium muscle strength but not for those who had medium genetic risk but high muscle strength. Associations were similar for ischemic and hemorrhagic stroke (although CIs were inconclusive for some of the associations).

Conclusion: Higher muscle strength was associated with lower stroke incidence in all individuals, including those with high genetic susceptibility. The increased genetic risk of overall and ischemic stroke was partly attenuated through increased muscle strength.
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http://dx.doi.org/10.1016/j.mayocp.2021.01.034DOI Listing
July 2021

Promoting physical activity in a multi-ethnic population at high risk of diabetes: the 48-month PROPELS randomised controlled trial.

BMC Med 2021 06 3;19(1):130. Epub 2021 Jun 3.

Diabetes Research Centre, College of Medicine, Biological Sciences and Psychology, University of Leicester, Leicester, UK.

Background: Physical activity is associated with a reduced risk of type 2 diabetes and cardiovascular disease but limited evidence exists for the sustained promotion of increased physical activity within diabetes prevention trials. The aim of the study was to investigate the long-term effectiveness of the Walking Away programme, an established group-based behavioural physical activity intervention with pedometer use, when delivered alone or with a supporting mHealth intervention.

Methods: Those at risk of diabetes (nondiabetic hyperglycaemia) were recruited from primary care, 2013-2015, and randomised to (1) Control (information leaflet); (2) Walking Away (WA), a structured group education session followed by annual group-based support; or (3) Walking Away Plus (WAP), comprising WA annual group-based support and an mHealth intervention delivering tailored text messages supported by telephone calls. Follow-up was conducted at 12 and 48 months. The primary outcome was accelerometer measured ambulatory activity (steps/day). Change in primary outcome was analysed using analysis of covariance with adjustment for baseline, randomisation and stratification variables.

Results: One thousand three hundred sixty-six individuals were randomised (median age = 61 years, ambulatory activity = 6638 steps/day, women = 49%, ethnic minorities = 28%). Accelerometer data were available for 1017 (74%) individuals at 12 months and 993 (73%) at 48 months. At 12 months, WAP increased their ambulatory activity by 547 (97.5% CI 211, 882) steps/day compared to control and were 1.61 (97.5% CI 1.05, 2.45) times more likely to achieve 150 min/week of moderate-to-vigorous physical activity. Differences were not maintained at 48 months. WA was no different to control at 12 or 48 months. Secondary anthropometric and health outcomes were largely unaltered in both intervention groups apart from small reductions in body weight in WA (~ 1 kg) at 12- and 48-month follow-up.

Conclusions: Combining a pragmatic group-based intervention with text messaging and telephone support resulted in modest changes to physical activity at 12 months, but changes were not maintained at 48 months.

Trial Registration: ISRCTN 83465245 (registered on 14 June 2012).
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http://dx.doi.org/10.1186/s12916-021-01997-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173914PMC
June 2021

Heterogeneity of Associations between Total and Types of Fish Intake and the Incidence of Type 2 Diabetes: Federated Meta-Analysis of 28 Prospective Studies Including 956,122 Participants.

Nutrients 2021 Apr 7;13(4). Epub 2021 Apr 7.

Postgraduate Program in Epidemiology Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil.

The association between fish consumption and new-onset type 2 diabetes is inconsistent and differs according to geographical location. We examined the association between the total and types of fish consumption and type 2 diabetes using individual participant data from 28 prospective cohort studies from the Americas (6), Europe (15), the Western Pacific (6), and the Eastern Mediterranean (1) comprising 956,122 participants and 48,084 cases of incident type 2 diabetes. Incidence rate ratios (IRRs) for associations of total fish, shellfish, fatty, lean, fried, freshwater, and saltwater fish intake and type 2 diabetes were derived for each study, adjusting for a consistent set of confounders and combined across studies using random-effects meta-analysis. We stratified all analyses by sex due to observed interaction ( = 0.002) on the association between fish and type 2 diabetes. In women, for each 100 g/week higher intake the IRRs (95% CIs) of type 2 diabetes were 1.02 (1.01-1.03, = 61%) for total fish, 1.04 (1.01-1.07, = 46%) for fatty fish, and 1.02 (1.00-1.04, = 33%) for lean fish. In men, all associations were null. In women, we observed variation by geographical location: IRRs for total fish were 1.03 (1.02-1.04, = 0%) in the Americas and null in other regions. In conclusion, we found evidence of a neutral association between total fish intake and type 2 diabetes in men, but there was a modest positive association among women with heterogeneity across studies, which was partly explained by geographical location and types of fish intake. Future research should investigate the role of cooking methods, accompanying foods and environmental pollutants, but meanwhile, existing dietary regional, national, or international guidelines should continue to guide fish consumption within overall healthy dietary patterns.
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http://dx.doi.org/10.3390/nu13041223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068031PMC
April 2021

Associations of Total Legume, Pulse, and Soy Consumption with Incident Type 2 Diabetes: Federated Meta-Analysis of 27 Studies from Diverse World Regions.

J Nutr 2021 05;151(5):1231-1240

School of Public Health, Physiotherapy & Sports Science, University College Dublin, Dublin, Ireland.

Background: The consumption of legumes is promoted as part of a healthy diet in many countries but associations of total and types of legume consumption with type 2 diabetes (T2D) are not well established. Analyses across diverse populations are lacking despite the availability of unpublished legume consumption data in prospective cohort studies.

Objective: To examine the prospective associations of total and types of legume intake with the risk of incident T2D.

Methods: Meta-analyses of associations between total legume, pulse, and soy consumption and T2D were conducted using a federated approach without physical data-pooling. Prospective cohorts were included if legume exposure and T2D outcome data were available and the cohort investigators agreed to participate. We estimated incidence rate ratios (IRRs) and CIs of associations using individual participant data including ≤42,473 incident cases among 807,785 adults without diabetes in 27 cohorts across the Americas, Eastern Mediterranean, Europe, and Western Pacific. Random-effects meta-analysis was used to combine effect estimates and estimate heterogeneity.

Results: Median total legume intake ranged from 0-140 g/d across cohorts. We observed a weak positive association between total legume consumption and T2D (IRR = 1.02, 95% CI: 1.01 to 1.04) per 20 g/d higher intake, with moderately high heterogeneity (I2 = 74%). Analysis by region showed no evidence of associations in the Americas, Eastern Mediterranean, and Western Pacific. The positive association in Europe (IRR = 1.05, 95% CI: 1.01 to 1.10, I2 = 82%) was mainly driven by studies from Germany, UK, and Sweden. No evidence of associations was observed for the consumption of pulses or soy.

Conclusions: These findings suggest no evidence of an association of legume intakes with T2D in several world regions. The positive association observed in some European studies warrants further investigation relating to overall dietary contexts in which legumes are consumed, including accompanying foods which may be positively associated with T2D.
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http://dx.doi.org/10.1093/jn/nxaa447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112771PMC
May 2021

Changes in soft drinks purchased by British households associated with the UK soft drinks industry levy: controlled interrupted time series analysis.

BMJ 2021 03 10;372:n254. Epub 2021 Mar 10.

Centre for Diet and Activity Research, MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge CB2 0QQ, UK

Objective: To determine changes in household purchases of drinks and confectionery one year after implementation of the UK soft drinks industry levy (SDIL).

Design: Controlled interrupted time series analysis.

Participants: Members of a panel of households reporting their purchasing on a weekly basis to a market research company (average weekly number of participants n=22 183), March 2014 to March 2019.

Intervention: A two tiered tax levied on manufacturers of soft drinks, announced in March 2016 and implemented in April 2018. Drinks with ≥8 g sugar/100 mL (high tier) are taxed at £0.24/L and drinks with ≥5 to <8 g sugar/100 mL (low tier) are taxed at £0.18/L. Drinks with <5 g sugar/100 mL (no levy) are not taxed.

Main Outcome Measures: Absolute and relative differences in the volume of, and amount of sugar in, soft drinks categories, all soft drinks combined, alcohol, and confectionery purchased per household per week one year after implementation of the SDIL compared with trends before the announcement of the SDIL.

Results: In March 2019, compared with the counterfactual estimated from pre-announcement trends, purchased volume of drinks in the high levy tier decreased by 155 mL (95% confidence interval 240.5 to 69.5 mL) per household per week, equivalent to 44.3% (95% confidence interval 59.9% to 28.7%), and sugar purchased in these drinks decreased by 18.0 g (95% confidence interval 32.3 to 3.6 g), or 45.9% (68.8% to 22.9%). Purchases of low tier drinks decreased by 177.3 mL (225.3 to 129.3 mL) per household per week, or 85.9% (95.1% to 76.7%), with a 12.5 g (15.4 to 9.5 g) reduction in sugar in these drinks, equivalent to 86.2% (94.2% to 78.1%). Despite no overall change in volume of no levy drinks purchased, there was an increase in sugar purchased of 15.3 g (12.6 to 17.9 g) per household per week, equivalent to 166.4% (94.2% to 238.5%). When all soft drinks were combined, the volume of drinks purchased did not change, but sugar decreased by 29.5 g (55.8 to 3.1 g), or 9.8% (17.9% to 1.8%). Purchases of confectionery and alcoholic drinks did not change.

Conclusions: Compared with trends before the SDIL was announced, one year after implementation, the volume of soft drinks purchased did not change. The amount of sugar in those drinks was 30 g, or 10%, lower per household per week-equivalent to one 250 mL serving of a low tier drink per person per week. The SDIL might benefit public health without harming industry.

Trial Registration: ISRCTN18042742.
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http://dx.doi.org/10.1136/bmj.n254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944367PMC
March 2021

Effectiveness of Minimal Contact Interventions: An RCT.

Am J Prev Med 2021 03;60(3):e111-e121

Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.

Introduction: Around 23% of adults worldwide are insufficiently active. Wearable devices paired with virtual coaching software could increase physical activity. The effectiveness of 3 minimal contact interventions (paper-based physical activity diaries, activity trackers, and activity trackers coupled with virtual coaching) in increasing physical activity energy expenditure and cardiorespiratory fitness were compared over 12 weeks among inactive adults.

Methods: This was an open label, parallel-group RCT. Inactive adults (aged ≥18 years, N=488) were randomized to no intervention (Control; n=121), paper-based diary (Diary; n=124), activity tracker (Activity Band; n=122), or activity tracker plus virtual coaching (Activity Band PLUS; n=121) groups. Coprimary outcomes included 12-week changes in physical activity energy expenditure and fitness (May 2012-January 2014). Analyses were conducted in 2019-2020.

Results: There were no differences between groups overall (physical activity energy expenditure: p=0.114, fitness: p=0.417). However, there was a greater increase in physical activity energy expenditure (4.21 kJ/kg/day, 95% CI=0.42, 8.00) in the Activity Band PLUS group than in the Diary group. There were also greater decreases in BMI and body fat percentage in the Activity Band PLUS group than in the Control group (BMI= -0.24 kg/m, 95% CI= -0.45, -0.03; body fat= -0.48%, 95% CI= -0.88, -0.08) and in theActivity Band PLUS group than in the Diary group (BMI= -0.30 kg/m, 95% CI= -0.50, -0.09; body fat= -0.57%, 95% CI= -0.97, -0.17).

Conclusions: Coupling activity trackers with virtual coaching may facilitate increases in physical activity energy expenditure compared with a traditional paper‒based physical activity diary intervention and improve some secondary outcomes compared with a traditional paper‒based physical activity diary intervention or no intervention.

Trial Registration: This study is registered at www.clinicaltrials.gov ISRCTN31844443.
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http://dx.doi.org/10.1016/j.amepre.2020.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899959PMC
March 2021

Independent and combined associations between fast-food outlet exposure and genetic risk for obesity: a population-based, cross-sectional study in the UK.

BMC Med 2021 02 15;19(1):49. Epub 2021 Feb 15.

UKCRC Centre for Diet and Activity Research (CEDAR), MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.

Background: Characteristics of the built environment, such as neighbourhood fast-food outlet exposure, are increasingly recognised as risk factors for unhealthy diet and obesity. Obesity also has a genetic component, with common genetic variants explaining a substantial proportion of population-level obesity susceptibility. However, it is not known whether and to what extent associations between fast-food outlet exposure and body weight are modified by genetic predisposition to obesity.

Methods: We used data from the Fenland Study, a population-based sample of 12,435 UK adults (mean age 48.6 years). We derived a genetic risk score associated with BMI (BMI-GRS) from 96 BMI-associated single nucleotide polymorphisms. Neighbourhood fast-food exposure was defined as quartiles of counts of outlets around the home address. We used multivariable regression models to estimate the associations of each exposure, independently and in combination, with measured BMI, overweight and obesity, and investigated interactions.

Results: We found independent associations between BMI-GRS and risk of overweight (RR = 1.34, 95% CI 1.23-1.47) and obesity (RR = 1.73, 95% CI 1.55-1.93), and between fast-food outlet exposure and risk of obesity (highest vs lowest quartile RR = 1.58, 95% CI 1.21-2.05). There was no evidence of an interaction of fast-food outlet exposure and genetic risk on BMI (P = 0.09), risk of overweight (P = 0.51), or risk of obesity (P = 0.27). The combination of higher BMI-GRS and highest fast-food outlet exposure was associated with 2.70 (95% CI 1.99-3.66) times greater risk of obesity.

Conclusions: Our study demonstrated independent associations of both genetic obesity risk and neighbourhood fast-food outlet exposure with adiposity. These important drivers of the obesity epidemic have to date been studied in isolation. Neighbourhood fast-food outlet exposure remains a potential target of policy intervention to prevent obesity and promote the public's health.
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http://dx.doi.org/10.1186/s12916-021-01902-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885578PMC
February 2021

Positive maternal attitudes to following healthy infant feeding guidelines attenuate the associations between infant appetitive traits and both infant milk intake and weight.

Appetite 2021 06 19;161:105124. Epub 2021 Jan 19.

MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, University of Cambridge, Cambridge, UK. Electronic address:

Appetitive traits influence food intake and weight gain throughout the life-course. Here, we investigated whether maternal attitudes to following healthy infant feeding guidelines could modify this association. Baseline data from 544 mother-infant formula-feeding dyads recruited to the Baby Milk Trial were included in this observational, cross-sectional analysis. Infant appetitive traits (food responsiveness and satiety responsiveness), maternal attitudes to following healthy infant feeding guidelines (self-efficacy, outcome-expectancy, intentions) and infant milk intakes were reported by mothers through questionnaires. Infant weight was measured using standard procedures. Associations between the maternal attitudes score or infant appetitive traits with infant milk intake and infant weight were evaluated in linear regression models adjusted for infant sex and age. To identify effect modification, the interaction term between the maternal attitudes score and infant appetitive trait was added to the model. Infants' mean age and weight were 2.3 months (SD = 0.9) and 5.5 kg (SD = 0.9), respectively. The mean daily infant milk intake reported by mothers was 895 ml/day (SD = 215). Higher maternal attitudes score was associated with lower infant milk intake (Beta = -68.4 ml/day/unit (95% CI: 96.6, -40.2)) and infant weight (Beta = -0.13 SD/unit (-0.25, -0.02)). The maternal attitudes score showed interactions with infant food responsiveness on infant milk intake (p = 0.049), and with infant satiety responsiveness on infant weight (p = 0.01). In both cases, a higher maternal attitudes score attenuated the associations between infant appetitive traits and those outcomes. This analysis provides evidence that positive maternal attitudes to following healthy infant feeding guidelines attenuate the effects of infant appetitive traits on infant milk intake and body weight.
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http://dx.doi.org/10.1016/j.appet.2021.105124DOI Listing
June 2021

The absolute and relative risk of type 2 diabetes after gestational diabetes: A systematic review and meta-analysis of 129 studies.

Diabetes Res Clin Pract 2021 Jan 15;171:108625. Epub 2020 Dec 15.

The Primary Care Unit, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, UK; MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, University of Cambridge, Cambridge, UK. Electronic address:

Aims: To estimate development of type 2 diabetes (T2DM) in women with previous gestational diabetes (GDM) and investigate characteristics associated with higher diagnoses, building on previous meta-analyses and exploring heterogeneity.

Methods: Systematic literature review of studies published up to October 2019. We included studies reporting progression to T2DM ≥6 months after pregnancy, if diagnostic methods were reported and ≥50 women with GDM participated. We conducted random-effects meta-analyses and meta-regression of absolute and relative T2DM risk.

Prospero Id: CRD42017080299.

Results: In 129 included studies, the percentage diagnosed with T2DM was 12% (95% confidence interval 8-16%) higher for each additional year after pregnancy, with a third developing diabetes within 15 years. Development was 18% (5-34%) higher per unit BMI at follow-up, and 57% (39-70%) lower in White European populations compared to others (adjusted for ethnicity and follow-up). Women with GDM had a relative risk of T2DM of 8.3 (6.5-10.6). 17.0% (15.1-19.0%) developed T2DM overall, although heterogeneity between studies was substantial (I 99.3%), and remained high after accounting for various study-level characteristics.

Conclusions: Percentage developing T2DM after GDM is highly variable. These findings highlight the need for sustained follow-up after GDM through screening, and interventions to reduce modifiable risk factors.
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http://dx.doi.org/10.1016/j.diabres.2020.108625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610694PMC
January 2021

Interaction Between GAD65 Antibodies and Dietary Fish Intake or Plasma Phospholipid n-3 Polyunsaturated Fatty Acids on Incident Adult-Onset Diabetes: The EPIC-InterAct Study.

Diabetes Care 2021 02 10;44(2):416-424. Epub 2020 Dec 10.

Medical Research Council Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, U.K.

Objective: Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes.

Research Design And Methods: We used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction [AP]) and multiplicative interactions between GAD65 antibody positivity (≥65 units/mL) and low fish/n-3 PUFA were assessed.

Results: The hazard of diabetes in antibody-positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52 [95% CI 1.76-3.63] and 2.48 [1.79-3.45]) compared with people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44 [95% CI 0.16-0.72] and 0.48 [0.24-0.72]) and multiplicative ( = 0.0465 and 0.0103) interactions. Individuals with high GAD65 antibody levels (≥167.5 units/mL) and low total plasma phospholipid n-3 PUFAs had a more than fourfold higher hazard of diabetes (HR 4.26 [2.70-6.72]) and an AP of 0.46 (0.12-0.80) compared with antibody-negative individuals with high n-3 PUFAs.

Conclusions: High fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.
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http://dx.doi.org/10.2337/dc20-1463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818317PMC
February 2021

Association of weight loss and weight loss maintenance following diabetes diagnosis by screening and incidence of cardiovascular disease and all-cause mortality: An observational analysis of the ADDITION-Europe trial.

Diabetes Obes Metab 2021 03 21;23(3):730-741. Epub 2020 Dec 21.

MRC Epidemiology Unit, School of Clinical Medicine, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.

Aims: Short-term weight loss may lead to remission of type 2 diabetes but the effect of maintained weight loss on cardiovascular disease (CVD) is unknown. We quantified the associations between changes in weight 5 years following a diagnosis of diabetes, and incident CVD events and mortality up to 10 years after diagnosis.

Materials And Methods: Observational analysis of the ADDITION-Europe trial of 2730 adults with screen-detected type 2 diabetes from the UK, Denmark and the Netherlands. We defined weight change based on the maintenance at 5 years of weight loss achieved during the year after diabetes diagnosis, and as 5-year overall change in weight. Incident CVD events (n = 229) and all-cause mortality (n = 225) from 5 to 10 years follow-up were ascertained from medical records.

Results: Gaining >2% weight during the year after diabetes diagnosis was associated with higher hazard of all-cause mortality versus maintaining weight [hazard ratio (95% confidence interval): 3.18 (1.30-7.82)]. Losing ≥5% weight 1 year after diagnosis was also associated with mortality, whether or not weight loss was maintained at 5 years: 2.47 (0.99-6.21) and 2.72 (1.17-6.30), respectively. Losing ≥10% weight over 5 years was associated with mortality among those with body mass index <30 kg/m [4.62 (1.87-11.42)]. Associations with CVD incidence were inconclusive.

Conclusions: Both weight loss and weight gain after screen-detected diabetes diagnosis were associated with higher mortality, but not CVD events, particularly among participants without obesity. The clinical implications of weight loss following a diagnosis of diabetes probably depend on its magnitude and timing, and may differ by body mass index status. Personalization of weight loss advice and support may be warranted.
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http://dx.doi.org/10.1111/dom.14278DOI Listing
March 2021

Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations.

Diabetes Care 2021 01 17;44(1):98-106. Epub 2020 Nov 17.

Unit of Nutrition and Cancer, Cancer Epidemiology Research Program and Translational Research Laboratory; Catalan Institute of Oncology - ICO, Group of Research on Nutrition and Cancer, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet of Llobregat, Barcelona, Spain.

Objective: Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes.

Research Design And Methods: We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants.

Results: We identified 11 genomic regions associated with plasma vitamin C ( < 5 × 10), with the strongest signal at , and 10 novel genetic loci including , , , , , , , , , and . Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10).

Conclusions: These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.
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http://dx.doi.org/10.2337/dc20-1328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783939PMC
January 2021

Genome-wide association analysis of type 2 diabetes in the EPIC-InterAct study.

Sci Data 2020 11 13;7(1):393. Epub 2020 Nov 13.

Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.

Type 2 diabetes (T2D) is a global public health challenge. Whilst the advent of genome-wide association studies has identified >400 genetic variants associated with T2D, our understanding of its biological mechanisms and translational insights is still limited. The EPIC-InterAct project, centred in 8 countries in the European Prospective Investigations into Cancer and Nutrition study, is one of the largest prospective studies of T2D. Established as a nested case-cohort study to investigate the interplay between genetic and lifestyle behavioural factors on the risk of T2D, a total of 12,403 individuals were identified as incident T2D cases, and a representative sub-cohort of 16,154 individuals was selected from a larger cohort of 340,234 participants with a follow-up time of 3.99 million person-years. We describe the results from a genome-wide association analysis between more than 8.9 million SNPs and T2D risk among 22,326 individuals (9,978 cases and 12,348 non-cases) from the EPIC-InterAct study. The summary statistics to be shared provide a valuable resource to facilitate further investigations into the genetics of T2D.
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http://dx.doi.org/10.1038/s41597-020-00716-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666191PMC
November 2020

Anticipatory changes in British household purchases of soft drinks associated with the announcement of the Soft Drinks Industry Levy: A controlled interrupted time series analysis.

PLoS Med 2020 11 12;17(11):e1003269. Epub 2020 Nov 12.

Centre for Diet and Activity Research, MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, United Kingdom.

Background: Sugar-sweetened beverage (SSB) consumption is positively associated with obesity, type 2 diabetes, and cardiovascular disease. The World Health Organization recommends that member states implement effective taxes on SSBs to reduce consumption. The United Kingdom Soft Drinks Industry Levy (SDIL) is a two-tiered tax, announced in March 2016 and implemented in April 2018. Drinks with ≥8 g of sugar per 100 ml (higher levy tier) are taxed at £0.24 per litre, drinks with ≥5 to <8 g of sugar per 100 ml (lower levy tier) are taxed at £0.18 per litre, and drinks with <5 g sugar per 100 ml (no levy) are not taxed. Milk-based drinks, pure fruit juices, drinks sold as powder, and drinks with >1.2% alcohol by volume are exempt. We aimed to determine if the announcement of the SDIL was associated with anticipatory changes in purchases of soft drinks prior to implementation of the SDIL in April 2018. We explored differences in the volume of and amount of sugar in household purchases of drinks in each levy tier at 2 years post announcement.

Methods And Findings: We used controlled interrupted time series to compare observed changes associated with the announcement of the SDIL to the counterfactual scenario of no announcement. We used data from Kantar Worldpanel, a commercial household purchasing panel with approximately 30,000 British members that includes linked nutritional data on purchases. We conducted separate analyses for drinks liable for the SDIL in the higher, lower, and no-levy tiers controlling with household purchase volumes of toiletries. At 2 years post announcement, there was no difference in volume of or sugar from purchases of higher-levy-tier drinks compared to the counterfactual of no announcement. In contrast, a reversal of the existing upward trend in volume (ml) of and amount of sugar (g) in purchases of lower-levy-tier drinks was seen. These changes led to a -96.1 ml (95% confidence interval [CI] -144.2 to -48.0) reduction in volume and -6.4 g (95% CI -9.8 to -3.1) reduction in sugar purchased in these drinks per household per week. There was a reversal of the existing downward trend in the amount of sugar in household purchases of the no-levy drinks but no change in volume purchased. At 2 years post announcement, these changes led to a 6.1 g (95% CI 3.9-8.2) increase in sugar purchased in these drinks per household per week. There was no evidence that volume of or amount of sugar in purchases of all drinks combined was different from the counterfactual. This is an observational study, and changes other than the SDIL may have been responsible for the results reported. Purchases consumed outside of the home were not accounted for.

Conclusions: The announcement of the UK SDIL was associated with reductions in volume and sugar purchased in lower-levy-tier drinks before implementation. These were offset by increases in sugar purchased from no-levy drinks. These findings may reflect reformulation of drinks from the lower levy to no-levy tier with removal of some but not all sugar, alongside changes in consumer attitudes and beliefs.

Trial Registration: ISRCTN Registry ISRCTN18042742.
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http://dx.doi.org/10.1371/journal.pmed.1003269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660521PMC
November 2020

The impact of adult behavioural weight management interventions on mental health: A systematic review and meta-analysis.

Obes Rev 2021 04 25;22(4):e13150. Epub 2020 Oct 25.

MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.

There is good evidence that behavioural weight management interventions improve physical health; however, the impact on mental health remains unclear. We evaluated the impact of behavioural weight management interventions on mental health-related outcomes in adults with overweight or obesity at intervention-end and 12 months from baseline. Eligible studies were randomized controlled trials (RCTs) or cluster RCTs of adult behavioural weight loss interventions reporting affect, anxiety, binge eating, body image, depression, emotional eating, quality of life, self-esteem and stress. We searched seven databases from inception to 7 May 2019 and included 43 articles reporting 42 RCTs. Eighteen studies were deemed to be at high risk of bias. We conducted random-effects meta-analyses, stratified analyses and meta-regression using Stata. Interventions generated greater improvements than comparators for depression, mental health-related quality of life and self-efficacy at intervention-end and 12 months from baseline. There was no difference between groups for anxiety, overall quality of life, self-esteem or stress at intervention-end. There was insufficient evidence to assess the impact on anxiety, binge eating, body image, emotional eating, affect, life satisfaction, self-esteem or stress at intervention-end and/or 12 months from baseline. Although evidence suggests that interventions benefit some aspects of mental health, high-quality, transparently reported RCTs measuring a range of mental health outcomes over longer durations are required to strengthen the evidence base.
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http://dx.doi.org/10.1111/obr.13150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116866PMC
April 2021

Meta-analysis investigating the role of interleukin-6 mediated inflammation in type 2 diabetes.

EBioMedicine 2020 Nov 21;61:103062. Epub 2020 Oct 21.

MRC Epidemiology Unit, University of Cambridge, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrookes Hospital, Cambridge CB2 0QQ, United Kingdom; Regeneron Genetics Center, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, United States.

Background: Evidence from animal models and observational epidemiology points to a role for chronic inflammation, in which interleukin 6 (IL-6) is a key player, in the pathophysiology of type 2 diabetes (T2D). However, it is unknown whether IL-6 mediated inflammation is implicated in the pathophysiology of T2D.

Methods: We performed a meta-analysis of 15 prospective studies to investigate associations between IL-6 levels and incident T2D including 5,421 cases and 31,562 non-cases. We also estimated the association of a loss-of-function missense variant (Asp358Ala) in the IL-6 receptor gene (IL6R), previously shown to mimic the effects of IL-6R inhibition, in a large trans-ethnic meta-analysis of six T2D case-control studies including 260,614 cases and 1,350,640 controls.

Findings: In a meta-analysis of 15 prospective studies, higher levels of IL-6 (per log pg/mL) were significantly associated with a higher risk of incident T2D (1·24 95% CI, 1·17, 1·32; P = 1 × 10). In a trans-ethnic meta-analysis of 260,614 cases and 1,350,640 controls, the IL6R Asp358Ala missense variant was associated with lower odds of T2D (OR, 0·98; 95% CI, 0·97, 0·99; P = 2 × 10). This association was not due to diagnostic misclassification and was consistent across ethnic groups. IL-6 levels mediated up to 5% of the association between higher body mass index and T2D.

Interpretation: Large-scale human prospective and genetic data provide evidence that IL-6 mediated inflammation is implicated in the etiology of T2D but suggest that the impact of this pathway on disease risk in the general population is likely to be small.

Funding: The EPICNorfolk study has received funding from the Medical Research Council (MRC) (MR/N003284/1, MC-UU_12015/1 and MC_PC_13048) and Cancer Research UK (C864/A14136). The Fenland Study is funded by the MRC (MC_UU_12015/1 and MC_PC_13046).
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http://dx.doi.org/10.1016/j.ebiom.2020.103062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581887PMC
November 2020

The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis.

PLoS Med 2020 10 16;17(10):e1003394. Epub 2020 Oct 16.

Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.

Background: Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis.

Methods And Findings: We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]-InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1-standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities.

Conclusions: Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D.
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http://dx.doi.org/10.1371/journal.pmed.1003394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567390PMC
October 2020

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 11 31;43(11):2660-2667. Epub 2020 Aug 31.

CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Objective: There is sparse evidence for the association of suitable food substitutions for red and processed meat on the risk of type 2 diabetes. We modeled the association between replacing red and processed meat with other protein sources and the risk of type 2 diabetes and estimated its population impact.

Research Design And Methods: The European Prospective Investigation into Cancer (EPIC)-InterAct case cohort included 11,741 individuals with type 2 diabetes and a subcohort of 15,450 participants in eight countries. We modeled the replacement of self-reported red and processed meat with poultry, fish, eggs, legumes, cheese, cereals, yogurt, milk, and nuts. Country-specific hazard ratios (HRs) for incident type 2 diabetes were estimated by Prentice-weighted Cox regression and pooled using random-effects meta-analysis.

Results: There was a lower hazard for type 2 diabetes for the modeled replacement of red and processed meat (50 g/day) with cheese (HR 0.90, 95% CI 0.83-0.97) (30 g/day), yogurt (0.90, 0.86-0.95) (70 g/day), nuts (0.90, 0.84-0.96) (10 g/day), or cereals (0.92, 0.88-0.96) (30 g/day) but not for replacements with poultry, fish, eggs, legumes, or milk. If a causal association is assumed, replacing red and processed meat with cheese, yogurt, or nuts could prevent 8.8%, 8.3%, or 7.5%, respectively, of new cases of type 2 diabetes.

Conclusions: Replacement of red and processed meat with cheese, yogurt, nuts, or cereals was associated with a lower rate of type 2 diabetes. Substituting red and processed meat by other protein sources may contribute to the prevention of incident type 2 diabetes in European populations.
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http://dx.doi.org/10.2337/dc20-1038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576430PMC
November 2020

Wearable-device-measured physical activity and future health risk.

Nat Med 2020 09 17;26(9):1385-1391. Epub 2020 Aug 17.

MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.

Use of wearable devices that monitor physical activity is projected to increase more than fivefold per half-decade. We investigated how device-based physical activity energy expenditure (PAEE) and different intensity profiles were associated with all-cause mortality. We used a network harmonization approach to map dominant-wrist acceleration to PAEE in 96,476 UK Biobank participants (mean age 62 years, 56% female). We also calculated the fraction of PAEE accumulated from moderate-to-vigorous-intensity physical activity (MVPA). Over the median 3.1-year follow-up period (302,526 person-years), 732 deaths were recorded. Higher PAEE was associated with a lower hazard of all-cause mortality for a constant fraction of MVPA (for example, 21% (95% confidence interval 4-35%) lower hazard for 20 versus 15 kJ kg d PAEE with 10% from MVPA). Similarly, a higher MVPA fraction was associated with a lower hazard when PAEE remained constant (for example, 30% (8-47%) lower hazard when 20% versus 10% of a fixed 15 kJ kg d PAEE volume was from MVPA). Our 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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http://dx.doi.org/10.1038/s41591-020-1012-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116559PMC
September 2020

Effectiveness and cost-effectiveness of the GoActive intervention to increase physical activity among UK adolescents: A cluster randomised controlled trial.

PLoS Med 2020 07 23;17(7):e1003210. Epub 2020 Jul 23.

UKCRC Centre for Diet and Activity Research, University of Cambridge, Cambridge, United Kingdom.

Background: Less than 20% of adolescents globally meet recommended levels of physical activity, and not meeting these recommended levels is associated with social disadvantage and rising disease risk. The determinants of physical activity in adolescents are multilevel and poorly understood, but the school's social environment likely plays an important role. We conducted a cluster randomised controlled trial to assess the effectiveness of a school-based programme (GoActive) to increase moderate-to-vigorous physical activity (MVPA) among adolescents.

Methods And Findings: Non-fee-paying, co-educational schools including Year 9 students in the UK counties of Cambridgeshire and Essex were eligible for inclusion. Within participating schools (n = 16), all Year 9 students were eligible and invited to participate. Participants were 2,862 13- to 14-year-olds (84% of eligible students). After baseline assessment, schools were computer-randomised, stratified by school-level pupil premium funding (below/above county-specific median) and county (control: 8 schools, 1,319 participants, mean [SD] participants per school n = 165 [62]; intervention: 8 schools, 1,543 participants, n = 193 [43]). Measurement staff were blinded to allocation. The iteratively developed, feasibility-tested 12-week intervention, aligned with self-determination theory, trained older adolescent mentors and in-class peer-leaders to encourage classes to conduct 2 new weekly activities. Students and classes gained points and rewards for engaging in any activity in or out of school. The primary outcome was average daily minutes of accelerometer-assessed MVPA at 10-month follow-up; a mixed-methods process evaluation evaluated implementation. Of 2,862 recruited participants (52.1% male), 2,167 (76%) attended 10-month follow-up measurements; we analysed the primary outcome for 1,874 participants (65.5%). At 10 months, there was a mean (SD) decrease in MVPA of 8.3 (19.3) minutes in the control group and 10.4 (22.7) minutes in the intervention group (baseline-adjusted difference [95% confidence interval] -1.91 minutes [-5.53 to 1.70], p = 0.316). The programme cost £13 per student compared with control; it was not cost-effective. Overall, 62.9% of students and 87.3% of mentors reported that GoActive was fun. Teachers and mentors commented that their roles in programme delivery were unclear. Implementation fidelity was low. The main methodological limitation of this study was the relatively affluent and ethnically homogeneous sample.

Conclusions: In this study, we observed that a rigorously developed school-based intervention was no more effective than standard school practice at preventing declines in adolescent physical activity. Interdisciplinary research is required to understand educational-setting-specific implementation challenges. School leaders and authorities should be realistic about expectations of the effect of school-based physical activity promotion strategies implemented at scale.

Trial Registration: ISRCTN Registry ISRCTN31583496.
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http://dx.doi.org/10.1371/journal.pmed.1003210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377379PMC
July 2020

Physical distancing interventions and incidence of coronavirus disease 2019: natural experiment in 149 countries.

BMJ 2020 07 15;370:m2743. Epub 2020 Jul 15.

MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.

Objective: To evaluate the association between physical distancing interventions and incidence of coronavirus disease 2019 (covid-19) globally.

Design: Natural experiment using interrupted time series analysis, with results synthesised using meta-analysis.

Setting: 149 countries or regions, with data on daily reported cases of covid-19 from the European Centre for Disease Prevention and Control and data on the physical distancing policies from the Oxford covid-19 Government Response Tracker.

Participants: Individual countries or regions that implemented one of the five physical distancing interventions (closures of schools, workplaces, and public transport, restrictions on mass gatherings and public events, and restrictions on movement (lockdowns)) between 1 January and 30 May 2020.

Main Outcome Measure: Incidence rate ratios (IRRs) of covid-19 before and after implementation of physical distancing interventions, estimated using data to 30 May 2020 or 30 days post-intervention, whichever occurred first. IRRs were synthesised across countries using random effects meta-analysis.

Results: On average, implementation of any physical distancing intervention was associated with an overall reduction in covid-19 incidence of 13% (IRR 0.87, 95% confidence interval 0.85 to 0.89; n=149 countries). Closure of public transport was not associated with any additional reduction in covid-19 incidence when the other four physical distancing interventions were in place (pooled IRR with and without public transport closure was 0.85, 0.82 to 0.88; n=72, and 0.87, 0.84 to 0.91; n=32, respectively). Data from 11 countries also suggested similar overall effectiveness (pooled IRR 0.85, 0.81 to 0.89) when school closures, workplace closures, and restrictions on mass gatherings were in place. In terms of sequence of interventions, earlier implementation of lockdown was associated with a larger reduction in covid-19 incidence (pooled IRR 0.86, 0.84 to 0.89; n=105) compared with a delayed implementation of lockdown after other physical distancing interventions were in place (pooled IRR 0.90, 0.87 to 0.94; n=41).

Conclusions: Physical distancing interventions were associated with reductions in the incidence of covid-19 globally. No evidence was found of an additional effect of public transport closure when the other four physical distancing measures were in place. Earlier implementation of lockdown was associated with a larger reduction in the incidence of covid-19. These findings might support policy decisions as countries prepare to impose or lift physical distancing measures in current or future epidemic waves.
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http://dx.doi.org/10.1136/bmj.m2743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360923PMC
July 2020

Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes: EPIC-InterAct case-cohort study in eight European countries.

BMJ 2020 07 8;370:m2194. Epub 2020 Jul 8.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Objective: To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes.

Design: Prospective case-cohort study.

Setting: Populations from eight European countries.

Participants: 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study.

Main Outcome Measure: Incident type 2 diabetes.

Results: In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis.

Conclusions: These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.
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http://dx.doi.org/10.1136/bmj.m2194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341350PMC
July 2020

The effect of referral to an open-group behavioural weight-management programme on the relative risk of normoglycaemia, non-diabetic hyperglycaemia and type 2 diabetes: Secondary analysis of the WRAP trial.

Diabetes Obes Metab 2020 11 15;22(11):2069-2076. Epub 2020 Jul 15.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.

Aim: To examine the impact of open-group behavioural weight-management programmes on the risk of diabetes among those with a body mass index (BMI) of ≥28 kg/m and those with non-diabetic hyperglycaemia (NDH).

Methods: This was a secondary analysis of data from the WRAP trial, in which participants (N = 1267; aged ≥18 years, BMI ≥ 28 kg/m ) were randomized to brief intervention (BI; self-help booklet), a weight-management programme (WW; formerly Weight Watchers) for 12 weeks, or WW for 52 weeks. We used multinomial logistic regression to examine the effect of intervention group on the risk of hyperglycaemia and diabetes at 12 months in all participants with glycaemic status at both time points (N = 480; 38%) and those with NDH at baseline (N = 387; 31%). We used mixed effects models and linear fixed effects models to examine the effect of intervention group on body weight and HbA1c at 12 months in people with NDH.

Results: There was a 61% relative reduction in the risk of NDH at the 12-month follow-up (12 weeks vs. BI: relative risk ratio [RRR] = 0.39 [95% CI 0.18, 0.87], P = .021; 52 weeks vs. BI: RRR = 0.38 [95% CI 0.17, 0.86], P = .020). For intervention effects on the risk of diabetes, confidence intervals were wide and overlapped 1 [12 weeks vs. BI: RRR = 0.49 [95% CI 0.12, 1.96], P = .312; 52 weeks vs. BI: RRR = 0.40 [95% CI 0.10, 1.63], P = .199). Participants with hyperglycaemia at baseline in the weight-management programme were more probable to have normoglycaemia at the 12-month follow-up [12-week programme vs. BI: RRR = 3.57 [95% CI 1.24, 10.29], P = .019; 52-week programme vs. BI: RRR = 4.14 [95% CI 1.42, 12.12], P = .009).

Conclusions: Open-group behavioural weight-management programmes can help to prevent the development of NDH in people with overweight and obesity and to normalize glycaemia in people with NDH.
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http://dx.doi.org/10.1111/dom.14123DOI Listing
November 2020

Use of the prevented fraction for the population to determine deaths averted by existing prevalence of physical activity: a descriptive study.

Lancet Glob Health 2020 07;8(7):e920-e930

Physical Activity for Health Research Centre, Institute of Sport, Physical Education, and Health Sciences, Moray House School of Education and Sport, University of Edinburgh, Edinburgh, UK.

Background: Disease and mortality burdens of unhealthy lifestyle behaviours are often reported. In contrast, the positive narrative around the burdens that an existing behaviour have averted is rarely acknowledged. We aimed to estimate the prevented fraction for the population (PFP) for premature mortality averted by physical activity on a global scale.

Methods: In this descriptive study, we obtained previously published data on physical activity prevalence (2001-16) and relative risks of all-cause mortality for 168 countries. We combined the data in Monte-Carlo simulations to estimate country-specific, mean PFP values, corresponding to percentage of mortality averted, and their 95% CIs. High prevented fractions indicated an increased proportion of deaths averted due to physical activity. Using mortality data for all people in a country aged 40-74 years, we estimated the number of premature deaths averted for all adults and by gender. We present the median and range of the prevented fractions globally, by WHO region, and by World Bank income classification.

Findings: The global median PFP was 15·0% (range 6·6-20·5), conservatively equating to 3·9 million (95% CI 2·5-5·6) premature deaths averted annually. The African region had the highest median prevented fraction (16·6% [range 12·1-20·5]) and the Americas had the lowest (13·1% [10·8-16·6]). Low-income countries tended to have higher prevented fractions (group median 17·9% [12·3-20·5]) than high-income countries (14·1% [6·6-17·8]). Globally, the median prevented fraction was higher for men (16·0% [7·8-20·7] than women (14·1% [5·0-20·4]).

Interpretation: Existing physical activity prevalence has contributed to averting premature mortality across all countries. PFP has utility as an advocacy tool to promote healthy lifestyle behaviours. By making the case of what has been achieved, the prevented fraction can show the value of current investment and services, which might be conducive to political support.

Funding: UK Medical Research Council, British Heart Foundation, Cancer Research UK, Economic and Social Research Council, National Institute for Health Research, Wellcome Trust, Heart Foundation Australia.
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http://dx.doi.org/10.1016/S2214-109X(20)30211-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303949PMC
July 2020

A randomised controlled trial of the effect of providing online risk information and lifestyle advice for the most common preventable cancers.

Prev Med 2020 09 29;138:106154. Epub 2020 May 29.

The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge School of Clinical Medicine, Box 113, Cambridge Biomedical Campus, Cambridge CB2 0SR, UK. Electronic address:

Few trial data are available concerning the impact of personalised cancer risk information on behaviour. This study assessed the short-term effects of providing personalised cancer risk information on cancer risk beliefs and self-reported behaviour. We randomised 1018 participants, recruited through the online platform Prolific, to either a control group receiving cancer-specific lifestyle advice or one of three intervention groups receiving their computed 10-year risk of developing one of the five most common preventable cancers either as a bar chart, a pictograph or a qualitative scale alongside the same lifestyle advice. The primary outcome was change from baseline in computed risk relative to an individual with a recommended lifestyle (RRI) at three months. Secondary outcomes included: health-related behaviours, risk perception, anxiety, worry, intention to change behaviour, and a newly defined concept, risk conviction. After three months there were no between-group differences in change in RRI (p = 0.71). At immediate follow-up, accuracy of absolute risk perception (p < 0.001), absolute and comparative risk conviction (p < 0.001) and intention to increase fruit and vegetables (p = 0.026) and decrease processed meat (p = 0.033) were higher in all intervention groups relative to the control group. The increases in accuracy and conviction were only seen in individuals with high numeracy and low baseline conviction, respectively. These findings suggest that personalised cancer risk information alongside lifestyle advice can increase short-term risk accuracy and conviction without increasing worry or anxiety but has little impact on health-related behaviour. Trial registration: ISRCTN17450583. Registered 30 January 2018.
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http://dx.doi.org/10.1016/j.ypmed.2020.106154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378571PMC
September 2020

Clinical and cost-effectiveness of a diabetes education and behavioural weight management programme versus a diabetes education programme in adults with a recent diagnosis of type 2 diabetes: study protocol for the Glucose Lowering through Weight management (GLoW) randomised controlled trial.

BMJ Open 2020 04 28;10(4):e035020. Epub 2020 Apr 28.

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, Cambridgeshire, UK.

Introduction: People with type 2 diabetes (T2D) can improve glycaemic control or even achieve remission through weight loss and reduce their use of medication and risk of cardiovascular disease. The Glucose Lowering through Weight management (GLoW) trial will evaluate whether a tailored diabetes education and behavioural weight management programme (DEW) is more effective and cost-effective than a diabetes education (DE) programme in helping people with overweight or obesity and a recent diagnosis of T2D to lower their blood glucose, lose weight and improve other markers of cardiovascular risk.

Methods And Analysis: This study is a pragmatic, randomised, single-blind, parallel group, two-arm, superiority trial. We will recruit 576 adults with body mass index>25 kg/m and diagnosis of T2D in the past 3 years and randomise them to a tailored DEW or a DE programme. Participants will attend measurement appointments at a local general practitioner practice or research centre at baseline, 6 and 12 months. The primary outcome is 12-month change in glycated haemoglobin. The effect of the intervention on the primary outcome will be estimated and tested using a linear regression model (analysis of covariance) including randomisation group and adjusted for baseline value of the outcome and the randomisation stratifiers. Participants will be included in the group to which they were randomised, under the intention-to-treat principle. Secondary outcomes include 6-month and 12-month changes in body weight, body fat percentage, systolic and diastolic blood pressure and lipid profile; probability of achieving good glycaemic control; probability of achieving remission from diabetes; probability of losing 5% and 10% body weight and modelled cardiovascular risk (UKPDS). An intention-to-treat within-trial cost-effectiveness analysis will be conducted from NHS and societal perspectives using participant-level data. Qualitative interviews will be conducted with participants to understand why and how the programme achieved its results and how participants manage their weight after the programme ends.

Ethics And Dissemination: Ethical approval was received from East of Scotland Research Ethics Service on 15 May 2018 (18/ES/0048). This protocol (V.3) was approved on 19 June 2019. Findings will be published in peer-reviewed scientific journals and communicated to other stakeholders as appropriate.

Trial Registration Number: ISRCTN18399564.
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http://dx.doi.org/10.1136/bmjopen-2019-035020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213851PMC
April 2020
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