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Background/objectives: The objective of this study was to describe serum lipid concentrations, including apolipoproteins A-I and B, in different diet groups., Subjects/methods: A cross-sectional analysis of a sample of 424 meat-eaters, 425 fish-eaters, 423 vegetarians and 422 vegans, matched on sex and age, from the European Prospective Investigation into Cancer and Nutrition-Oxford cohort. Serum concentrations of total, and high-density lipoprotein (HDL) cholesterol, as well as apolipoproteins A-I and B were measured, and serum non-HDL cholesterol was calculated., Results: Vegans had the lowest body mass index (BMI) and the highest and lowest intakes of polyunsaturated and saturated fat, respectively. After adjustment for age, alcohol and physical activity, compared with meat-eaters, fish-eaters and vegetarians, serum concentrations of total and non-HDL cholesterol and apolipoprotein B were significantly lower in vegans. Serum apolipoprotein A-I concentrations did not differ between the diet groups. In males, the mean serum total cholesterol concentration was 0.87 mmol/l lower in vegans than in meat-eaters; after further adjustment for BMI this difference was 0.76 mmol/l. In females, the difference in total cholesterol between these two groups was 0.6 mmol/l, and after further adjustment for BMI was 0.55 mmol/l. [corrected]., Conclusions: In this study, which included a large number of vegans, serum total cholesterol and apolipoprotein B concentrations were lower in vegans compared with meat-eaters, fish-eaters and vegetarians. A small proportion of the observed differences in serum lipid concentrations was explained by differences in BMI, but a large proportion is most likely due to diet.

Thearubigins (TR) are polymeric flavanol-derived compounds formed during the fermentation of tea leaves. Comprising ∼70% of total polyphenols in black tea, TR may contribute majorly to its beneficial effects on health. To date, there is no appropriate food composition data on TR, although several studies have used data from the US Department of Agriculture (USDA) database to estimate TR intakes. We aimed to estimate dietary TR in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and assess the impact of including TR or not in the calculation of the total dietary flavonoid intake. Dietary data were collected using a single standardized 24-h dietary recall interviewer-administered to 36 037 subjects aged 35-74 years. TR intakes were calculated using the USDA database. TR intakes ranged from 0.9 mg/day in men from Navarra and San Sebastian in Spain to 532.5 mg/day in men from UK general population. TR contributed <5% to the total flavonoid intake in Greece, Spain and Italy, whereas in the UK general population, TR comprised 48% of the total flavonoids. High heterogeneity in TR intake across the EPIC countries was observed. This study shows that total flavonoid intake may be greatly influenced by TR, particularly in high black tea-consuming countries. Further research on identification and quantification of TR is needed to get more accurate dietary TR estimations.

Aims/hypothesis: A diet rich in meat has been reported to contribute to the risk of type 2 diabetes. The present study aims to investigate the association between meat consumption and incident type 2 diabetes in the EPIC-InterAct study, a large prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study., Methods: During 11.7 years of follow-up, 12,403 incident cases of type 2 diabetes were identified among 340,234 adults from eight European countries. A centre-stratified random subsample of 16,835 individuals was selected in order to perform a case-cohort design. Prentice-weighted Cox regression analyses were used to estimate HR and 95% CI for incident diabetes according to meat consumption., Results: Overall, multivariate analyses showed significant positive associations with incident type 2 diabetes for increasing consumption of total meat (50 g increments: HR 1.08; 95% CI 1.05, 1.12), red meat (HR 1.08; 95% CI 1.03, 1.13) and processed meat (HR 1.12; 95% CI 1.05, 1.19), and a borderline positive association with meat iron intake. Effect modifications by sex and class of BMI were observed. In men, the results of the overall analyses were confirmed. In women, the association with total and red meat persisted, although attenuated, while an association with poultry consumption also emerged (HR 1.20; 95% CI 1.07, 1.34). These associations were not evident among obese participants., Conclusions/interpretation: This prospective study confirms a positive association between high consumption of total and red meat and incident type 2 diabetes in a large cohort of European adults.

Aims/hypothesis: Observational studies suggest that metformin may reduce cancer risk by approximately one-third. We examined cancer outcomes and all-cause mortality in published randomised controlled trials (RCTs)., Methods: RCTs comparing metformin with active glucose-lowering therapy or placebo/usual care, with minimum 500 participants and 1-year follow-up, were identified by systematic review. Data on cancer incidence and all-cause mortality were obtained from publications or by contacting investigators. For two trials, cancer incidence data were not available; cancer mortality was used as a surrogate. Summary RRs, 95% CIs and I (2)statistics for heterogeneity were calculated by fixed effects meta-analysis., Results: Of 4,039 abstracts identified, 94 publications described 14 eligible studies. RRs for cancer were available from 11 RCTs with 398 cancers during 51,681 person-years. RRs for all-cause mortality were available from 13 RCTs with 552 deaths during 66,447 person-years. Summary RRs for cancer outcomes in people randomised to metformin compared with any comparator were 1.02 (95% CI 0.82, 1.26) across all trials, 0.98 (95% CI 0.77, 1.23) in a subgroup analysis of active-comparator trials and 1.36 (95% CI 0.74, 2.49) in a subgroup analysis of placebo/usual care comparator trials. The summary RR for all-cause mortality was 0.94 (95% CI 0.79, 1.12) across all trials., Conclusions/interpretation: Meta-analysis of currently available RCT data does not support the hypothesis that metformin lowers cancer risk by one-third. Eligible trials also showed no significant effect of metformin on all-cause mortality. However, limitations include heterogeneous comparator types, absent cancer data from two trials, and short follow-up, especially for mortality.

Background/objectives: Cross-sectionally, educational attainment is strongly associated with the prevalence of obesity, but this association is less clear for weight change during adult life. The objective of this study is to examine the association between educational attainment and weight change during adult life in the European Prospective Investigation into Cancer and Nutrition (EPIC)., Subjects/methods: EPIC is a cohort study with 361,467 participants and up to 10 years of follow-up. Educational attainment was categorized according to the highest obtained school level (primary school or less, vocational secondary training, other secondary education and university). Multivariate mixed-effects linear regression models were used to study education in relation to weight at age 20 years (self-reported), to annual change in weight between age 20 years and measured weight at recruitment, and to annual change in weight during follow-up time., Results: Higher educational attainment was associated with on average a lower body mass index (BMI) at age 20 years and a lower increase in weight up to recruitment (highest vs lowest educational attainment in men: -60 g per year (95% confidence interval (CI) -80; -40), women -110 g per year (95% CI -130; -80)). Although during follow-up after recruitment an increase in body weight was observed in all educational levels, gain was lowest in men and women with a university degree (high vs low education -120 g per year (95% CI -150; -90) and -70 g per year (95% CI -90; -60), respectively)., Conclusions: Existing differences in BMI between higher and lower educated individuals at early adulthood became more pronounced during lifetime, which possibly impacts on obesity-related chronic disease risk in persons with lower educational attainment.

Background/objectives: Evidence from prospective studies is consistent in showing an inverse association between dietary fibre intake and risk of ischaemic heart disease (IHD), but whether dietary fibre from various food sources differ in their effect on IHD risk is less clear. The objective of this study was to assess the associations of total and food sources of dietary fibre with IHD mortality in the European Prospective Investigation into Cancer and Nutrition-Heart study., Subjects/methods: Participants were 306,331 men and women from eight European countries. Dietary fibre intake was assessed using centre or country-specific diet questionnaires and calibrated using a 24-h diet recall., Results: After an average follow-up of 11.5 years, there were 2381 IHD deaths among participants without cardiovascular disease at baseline. The calibrated intake of dietary fibre was inversely related with IHD mortality; each 10 g/day was associated with a 15% lower risk (relative risk (RR) 0.85; 95% confidence interval (CI): 0.73-0.99, P=0.031). There was no difference in the associations of the individual food sources of dietary fibre with the risk of IHD mortality; RR for each 5 g/day higher cereal fibre intake was 0.91 (CI: 0.82-1.01), RR for each 2.5 g/day fruit fibre intake was 0.94 (CI: 0.88-1.01) and RR for each 2.5 g/day vegetable fibre intake was 0.90 (95% CI: 0.76-1.07)., Conclusion: A higher consumption of dietary fibre is associated with a lower risk of fatal IHD with no clear difference in the association with IHD for fibre from cereals, fruits or vegetables.

Background: Insulin-like growth factors (IGFs) and their binding proteins (BPs) regulate cell differentiation, proliferation and apoptosis, and may have a role in the aetiology of various cancers. Information on their role in pancreatic cancer is limited and was examined here in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition., Methods: Serum concentrations of IGF-I and IGFBP-3 were measured using enzyme-linked immunosorbent assays in 422 cases and 422 controls matched on age, sex, study centre, recruitment date, and time since last meal. Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounding variables., Results: Neither circulating levels of IGF-I (OR=1.21, 95% CI 0.75-1.93 for top vs bottom quartile, P-trend 0.301), IGFBP-3 (OR=1.00, 95% CI 0.66-1.51, P-trend 0.79), nor the molar IGF-I/IGFBP-3 ratio, an indicator of free IGF-I level (OR=1.22, 95% CI 0.75-1.97, P-trend 0.27), were statistically significantly associated with the risk of pancreatic cancer. In a cross-classification, however, a high concentration of IGF-I with concurrently low levels of IGFBP-3 was related to an increased risk of pancreatic cancer (OR=1.72, 95% CI 1.05-2.83; P-interaction=0.154)., Conclusion: On the basis of these results, circulating levels of components of the IGF axis do not appear to be the risk factors for pancreatic cancer. However, on the basis of the results of a subanalysis, it cannot be excluded that a relatively large amount of IGF-1 together with very low levels of IGFBP-3 might still be associated with an increase in pancreatic cancer risk.

Objective: To study the association between adherence to the Mediterranean dietary pattern (MDP) and risk of developing type 2 diabetes, across European countries., Research Design and Methods: We established a case-cohort study including 11,994 incident type 2 diabetic case subjects and a stratified subcohort of 15,798 participants selected from a total cohort of 340,234 participants with 3.99 million person-years of follow-up, from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The relative Mediterranean diet score (rMED) (score range 0-18) was used to assess adherence to MDP on the basis of reported consumption of nine dietary components characteristic of the Mediterranean diet. Cox proportional hazards regression, modified for the case-cohort design, was used to estimate the association between rMED and risk of type 2 diabetes, adjusting for confounders., Results: The multiple adjusted hazard ratios of type 2 diabetes among individuals with medium (rMED 7-10 points) and high adherence to MDP (rMED 11-18 points) were 0.93 (95% CI 0.86-1.01) and 0.88 (0.79-0.97), respectively, compared with individuals with low adherence to MDP (0-6 points) (P for trend 0.013). The association between rMED and type 2 diabetes was attenuated in people <50 years of age, in obese participants, and when the alcohol, meat, and olive oil components were excluded from the score., Conclusions: In this large prospective study, adherence to the MDP, as defined by rMED, was associated with a small reduction in the risk of developing type 2 diabetes in this European population.

Aims/hypothesis: Studying gene-lifestyle interaction may help to identify lifestyle factors that modify genetic susceptibility and uncover genetic loci exerting important subgroup effects. Adequately powered studies with prospective, unbiased, standardised assessment of key behavioural factors for gene-lifestyle studies are lacking. This case-cohort study aims to investigate how genetic and potentially modifiable lifestyle and behavioural factors, particularly diet and physical activity, interact in their influence on the risk of developing type 2 diabetes., Methods: Incident cases of type 2 diabetes occurring in European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts between 1991 and 2007 from eight of the ten EPIC countries were ascertained and verified. Prentice-weighted Cox regression and random-effects meta-analyses were used to investigate differences in diabetes incidence by age and sex., Results: A total of 12,403 verified incident cases of type 2 diabetes occurred during 3.99 million person-years of follow-up of 340,234 EPIC participants eligible for InterAct. We defined a centre-stratified subcohort of 16,154 individuals for comparative analyses. Individuals with incident diabetes who were randomly selected into the subcohort (n = 778) were included as cases in the analyses. All prevalent diabetes cases were excluded from the study. InterAct cases were followed-up for an average of 6.9 years; 49.7% were men. Mean baseline age and age at diagnosis were 55.6 and 62.5 years, mean BMI and waist circumference values were 29.4 kg/m(2) and 102.7 cm in men, and 30.1 kg/m(2) and 92.8 cm in women, respectively. Risk of type 2 diabetes increased linearly with age, with an overall HR of 1.56 (95% CI 1.48-1.64) for a 10 year age difference, adjusted for sex. A male excess in the risk of incident diabetes was consistently observed across all countries, with a pooled HR of 1.51 (95% CI 1.39-1.64), adjusted for age., Conclusions/interpretation: InterAct is a large, well-powered, prospective study that will inform our understanding of the interplay between genes and lifestyle factors on the risk of type 2 diabetes development.

Background/objectives: Vegans, and to a lesser extent vegetarians, have low average circulating concentrations of vitamin B12; however, the relation between factors such as age or time on these diets and vitamin B12 concentrations is not clear. The objectives of this study were to investigate differences in serum vitamin B12 and folate concentrations between omnivores, vegetarians and vegans and to ascertain whether vitamin B12 concentrations differed by age and time on the diet., Subjects/methods: A cross-sectional analysis involving 689 men (226 omnivores, 231 vegetarians and 232 vegans) from the European Prospective Investigation into Cancer and Nutrition Oxford cohort., Results: Mean serum vitamin B12 was highest among omnivores (281, 95% CI: 270-292 pmol/l), intermediate among vegetarians (182, 95% CI: 175-189 pmol/l) and lowest among vegans (122, 95% CI: 117-127 pmol/l). In all, 52% of vegans, 7% of vegetarians and one omnivore were classified as vitamin B12 deficient (defined as serum vitamin B12 <118 pmol/l). There was no significant association between age or duration of adherence to a vegetarian or a vegan diet and serum vitamin B12. In contrast, folate concentrations were highest among vegans, intermediate among vegetarians and lowest among omnivores, but only two men (both omnivores) were categorized as folate deficient (defined as serum folate <6.3 nmol/l)., Conclusion: Vegans have lower vitamin B12 concentrations, but higher folate concentrations, than vegetarians and omnivores. Half of the vegans were categorized as vitamin B12 deficient and would be expected to have a higher risk of developing clinical symptoms related to vitamin B12 deficiency.

Objective: To describe dietary protein intakes and their food sources among 27 redefined centres in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC)., Methods: Between 1995 and 2000, 36 034 persons, aged between 35 and 74 years, were administered a standardized 24-h dietary recall (24-HDR) using a computerized interview software programme (EPIC-SOFT). Intakes (g/day) of total, animal and plant proteins were estimated using the standardized EPIC Nutrient Database (ENDB). Mean intakes were adjusted for age, and weighted by season and day of recall., Results: Mean total and animal protein intakes were highest in the Spanish centres among men, and in the Spanish and French centres among women; the lowest mean intakes were observed in the UK health-conscious group, in Greek men and women, and in women in Potsdam. Intake of plant protein was highest among the UK health-conscious group, followed by some of the Italian centres and Murcia, whereas Sweden and Potsdam had the lowest intake. Cereals contributed to the highest proportion of plant protein in all centres. The combined intake of legumes, vegetables and fruit contributed to a greater proportion of plant protein in the southern than in the northern centres. Total meat intake (with some heterogeneity across subtypes of meat) was, with few exceptions, the most important contributor to animal protein in all centres, followed by dairy and fish products., Conclusions: This study shows that intake of protein, especially of animal origin, differs across the 10 European countries, and also shows some differences in food sources of protein across Europe.