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1.
  • Ederle, Joerg, et al. (author)
  • Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
  • 2010
  • In: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
  • Journal article (peer-reviewed)abstract
    • Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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2.
  • Langenberg, C., et al. (author)
  • Design and cohort description of the InterAct Project : an examination of the interaction of genetic and lifestyle factors on the incidence of type 2 diabetes in the EPIC Study
  • 2011
  • In: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 54:9, s. 2272-2282
  • Journal article (peer-reviewed)abstract
    • 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. 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. 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. 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.
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3.
  • Bendinelli, B., et al. (author)
  • Association between dietary meat consumption and incident type 2 diabetes : the EPIC-InterAct study
  • 2013
  • In: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 56:1, s. 47-59
  • Journal article (peer-reviewed)abstract
    • 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.
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4.
  • Molina-Montes, E., et al. (author)
  • Dietary intake of iron, heme-iron and magnesium and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort
  • 2012
  • In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 131:7
  • Journal article (peer-reviewed)abstract
    • Several studies support a protective effect of dietary magnesium against type 2 diabetes, but a harmful effect for iron. As diabetes has been linked to pancreatic cancer, intake of these nutrients may be also associated with this cancer. We examined the association between dietary intake of magnesium, total iron and heme-iron and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. In total, 142,203 men and 334,999 women, recruited between 1992 and 2000, were included. After an average follow-up of 11.3 years, 396 men and 469 women developed exocrine pancreatic cancer. Hazard ratios and 95% confidence intervals (CIs) were obtained using Cox regression stratified by age and center, and adjusted for energy intake, smoking status, height, weight, and self-reported diabetes status. Neither intake of magnesium, total iron nor heme-iron was associated with pancreatic cancer risk. In stratified analyses, a borderline inverse association was observed among overweight men (body mass index, =25 kg/m2) with magnesium (HRper 100 mg/day increase = 0.79, 95% CI = 0.631.01) although this was less apparent using calibrated intake. In female smokers, a higher intake of heme-iron was associated with a higher pancreatic cancer risk (HR per 1 mg/day increase = 1.38, 95% CI = 1.101.74). After calibration, this risk increased significantly to 2.5-fold (95% CI = 1.225.28). Overall, dietary magnesium, total iron and heme-iron were not associated with pancreatic cancer risk during the follow-up period. Our observation that heme-iron was associated with increased pancreatic cancer risk in female smokers warrants replication in additional study populations.
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5.
  • North, R. L., et al. (author)
  • The state of Lake Simcoe (Ontario, Canada) : the effects of multiple stressors on phosphorus and oxygen dynamics
  • 2013
  • In: Inland Waters. - 2044-2041 .- 2044-205X. ; 3:1, s. 51-74
  • Journal article (peer-reviewed)abstract
    • Lake Simcoe, the largest lake in southern Ontario outside of the Laurentian Great Lakes, is affected by numerous stressors including eutrophication resulting from total phosphorus (TP) loading, climate change, and invasions of exotic species. We synthesized the long-term responses of Lake Simcoe to these stressors by assessing trends in water quality and biological composition over multiple trophic levels. Evidence for climate change included increasing thermal stability of the lake and changes in subfossil diatom communities over time. Although the deep water dissolved oxygen (O-2) minimum has increased significantly since TP load reductions, it is still below estimated historical values and the Lake Simcoe Protection Plan end-of-summer target level of 7 mg O-2 L-1. Low deep water O-2 concentrations corresponded with a decline in coldwater fish abundance. Since 1980, some nutrient concentrations have decreased (spring TP) while others have increased (silica), but many show no obvious changes (ice-free TP, nitrate, ammonium). Increases in water clarity, combined with declines in chlorophyll a and phytoplankton biovolumes in Cook's Bay, were temporally consistent with declines in TP loading and the lake-wide establishment of dreissenid mussels as a major component of the Lake Simcoe ecosystem. Using an investigative tool, we identified 2 periods when abrupt shifts potentially occurred in multiple parameters: 1986 and 1995-1997. Additional ecosystem level changes such as declines in zooplankton, declines in offshore benthic invertebrate abundance, and increased nearshore invertebrate abundance likely reflect the effects of invasive species. The interaction of these multiple stressors have significantly altered the Lake Simcoe ecosystem.
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6.
  • Rohrmann, S., et al. (author)
  • The association of education with long-term weight change in the EPIC-PANACEA cohort
  • 2012
  • In: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 66:8, s. 957-963
  • Journal article (peer-reviewed)abstract
    • 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.
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7.
  • Ekelund, U., et al. (author)
  • Physical activity reduces the risk of incident type 2 diabetes in general and in abdominally lean and obese men and women : the EPIC-InterAct Study
  • 2012
  • In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 55:7, s. 1944-1952
  • Journal article (peer-reviewed)abstract
    • We examined the independent and combined associations of physical activity and obesity with incident type 2 diabetes in men and women. The InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a randomly selected subcohort of 16,154 individuals, drawn from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. Physical activity was assessed by a four-category index. Obesity was measured by BMI and waist circumference (WC). Associations between physical activity, obesity and case-ascertained incident type 2 diabetes were analysed by Cox regression after adjusting for educational level, smoking status, alcohol consumption and energy intake. In combined analyses, individuals were stratified according to physical activity level, BMI and WC. A one-category difference in physical activity (equivalent to approximately 460 and 365 kJ/day in men and women, respectively) was independently associated with a 13% (HR 0.87, 95% CI 0.80, 0.94) and 7% (HR 0.93, 95% CI 0.89, 0.98) relative reduction in the risk of type 2 diabetes in men and women, respectively. Lower levels of physical activity were associated with an increased risk of diabetes across all strata of BMI. Comparing inactive with active individuals, the HRs were 1.44 (95% CI 1.11, 1.87) and 1.38 (95% CI 1.17, 1.62) in abdominally lean and obese inactive men, respectively, and 1.57 (95% CI 1.19, 2.07) and 1.19 (95% CI 1.01, 1.39) in abdominally lean and obese inactive women, respectively. Physical activity is associated with a reduction in the risk of developing type 2 diabetes across BMI categories in men and women, as well as in abdominally lean and obese men and women.
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8.
  • Grote, V. A., et al. (author)
  • Diabetes mellitus, glycated haemoglobin and C-peptide levels in relation to pancreatic cancer risk : a study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
  • 2011
  • In: Diabetologia. - New York : Springer-Verlag New York. - 0012-186X .- 1432-0428. ; 54:12, s. 3037-3046
  • Journal article (peer-reviewed)abstract
    • Aims/hypothesis: There has been long-standing debate about whether diabetes is a causal risk factor for pancreatic cancer or a consequence of tumour development. Prospective epidemiological studies have shown variable relationships between pancreatic cancer risk and blood markers of glucose and insulin metabolism, overall and as a function of lag times between marker measurements (blood donation) and date of tumour diagnosis.Methods: Pre-diagnostic levels of HbA(1c) and C-peptide were measured for 466 participants with pancreatic cancer and 466 individually matched controls within the European Prospective Investigation into Cancer and Nutrition. Conditional logistic regression models were used to estimate ORs for pancreatic cancer.Results: Pancreatic cancer risk gradually increased with increasing pre-diagnostic HbA(1c) levels up to an OR of 2.42 (95% CI 1.33, 4.39 highest [>= 6.5%, 48 mmol/mol] vs lowest [<= 5.4%, 36 mmol/mol] category), even for individuals with HbA(1c) levels within the non-diabetic range. C-peptide levels showed no significant relationship with pancreatic cancer risk, irrespective of fasting status. Analyses showed no clear trends towards increasing hyperglycaemia (as marked by HbA(1c) levels) or reduced pancreatic beta cell responsiveness (as marked by C-peptide levels) with decreasing time intervals from blood donation to cancer diagnosis.Conclusions/interpretation: Our data on HbA(1c) show that individuals who develop exocrine pancreatic cancer tend to have moderate increases in HbA(1c) levels, relatively independently of obesity and insulin resistance-the classic and major risk factors for type 2 diabetes. While there is no strong difference by lag time, more data are needed on this in order to reach a firm conclusion.
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9.
  • Rohrmann, S., et al. (author)
  • Concentrations of IGF-I and IGFBP-3 and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition
  • 2012
  • In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 106, s. 1004-1010
  • Journal article (peer-reviewed)abstract
    • 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 (O=R1.00, 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-interaction0.154). 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. © 2012 Cancer Research UK All rights reserved.
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10.
  • Zamora-Ros, R., et al. (author)
  • Impact of thearubigins on the estimation of total dietary flavonoids in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
  • 2013
  • In: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 67:7, s. 779-782
  • Journal article (peer-reviewed)abstract
    • Thearubigins (TR) are polymeric flavanol-derived compounds formed during the fermentation of tea leaves. Comprising similar to 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.
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