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21.
  • Qi, Qibin, et al. (författare)
  • FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals.
  • 2014
  • Ingår i: Human Molecular Genetics. - Oxford University Press. - 0964-6906. ; 23:25, s. 6961-6972
  • Tidskriftsartikel (refereegranskat)abstract
    • FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
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22.
  • Ricci, Cristian, et al. (författare)
  • Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke : : EPIC-CVD case-cohort study
  • 2018
  • Ingår i: BMJ (Online). - BMJ Publishing Group. - 0959-8138. ; 361
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke. Design Multicentre case-cohort study. Setting A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries. Participants 32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison. Main outcome measures Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke). Results There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events. Conclusions Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption.
23.
  • Ricci, Cristian, et al. (författare)
  • Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke EPIC-CVD case-cohort study
  • 2018
  • Ingår i: BMJ. British Medical Journal. - BMJ PUBLISHING GROUP. - 1756-1833. ; 361
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke. DESIGN Multicentre case-cohort study. SETTING A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries. PARTICIPANTS 32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison. MAIN OUTCOME MEASURES Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke). RESULTS There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/ day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events. CONCLUSIONS Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption.
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24.
  • Sacerdote, Carlotta, et al. (författare)
  • Lower educational level is a predictor of incident type 2 diabetes in European countries : The EPIC-InterAct study
  • 2012
  • Ingår i: International Journal of Epidemiology. - 0300-5771. ; 41:4, s. 1162-1173
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Type 2 diabetes mellitus ( T2DM) is one of the most common chronic diseases worldwide. In high- income countries, low socioeconomic status seems to be related to a high incidence of T2DM, but very little is known about the intermediate factors of this relationship.Method We performed a case-cohort study in eight Western European countries nested in the EPIC study (n = 340 234, 3.99 million person-years of follow-up). A random sub-cohort of 16 835 individuals and a total of 12 403 incident cases of T2DM were identified. Crude and multivariate-adjusted hazard ratios (HR) were estimated for each country and pooled across countries using meta-analytical methods. Age-, gender- and country-specific relative indices of inequality (RII) were used as the measure of educational level and RII tertiles were analysed.Results Compared with participants with a high educational level (RII tertile 1), participants with a low educational level (RII tertile 3) had a higher risk of T2DM [HR: 1.77, 95% confidence interval (CI): 1.69-1.85; P-trend < 0.01]. The HRs adjusted for physical activity, smoking status and propensity score according to macronutrient intake were very similar to the crude HR (adjusted HR: 1.67, 95% CI: 1.52-1.83 in men; HR: 1.88, 95% CI: 1.73-2.05 in women). The HRs were attenuated only when they were further adjusted for BMI (BMI-adjusted HR: 1.36, 95% CI: 1.23-1.51 in men; HR: 1.32, 95% CI: 1.20-1.45 in women).Conclusion This study demonstrates the inequalities in the risk of T2DM in Western European countries, with an inverse relationship between educational level and risk of T2DM that is only partially explained by variations in BMI.
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25.
  • Scott, Robert A, et al. (författare)
  • Common Genetic Variants Highlight the Role of Insulin Resistance and Body Fat Distribution in Type 2 Diabetes, Independent of Obesity
  • 2014
  • Ingår i: Diabetes. - 0012-1797. ; 63:12, s. 4378-4387
  • Tidskriftsartikel (refereegranskat)abstract
    • We aimed to validate genetic variants as instruments for insulin resistance and secretion, to characterize their association with intermediate phenotypes, and to investigate their role in type 2 diabetes (T2D) risk among normal-weight, overweight, and obese individuals. We investigated the association of genetic scores with euglycemic-hyperinsulinemic clamp- and oral glucose tolerance test-based measures of insulin resistance and secretion and a range of metabolic measures in up to 18,565 individuals. We also studied their association with T2D risk among normal-weight, overweight, and obese individuals in up to 8,124 incident T2D cases. The insulin resistance score was associated with lower insulin sensitivity measured by M/I value (beta in SDs per allele [95% CI], -0.03 [-0.04, -0.01]; P = 0.004). This score was associated with lower BMI (-0.01 [-0.01, -0.0]; P = 0.02) and gluteofemoral fat mass (-0.03 [-0.05,-0.02; P = 1.4x10(-6) and with higher alanine transaminase (0.02 [0.01, 0.03]; P = 0.002) and gamma-glutamyl transferase (0.02 [0.01, 0.03]; P = 0.001). While the secretion score had a stronger association with T2D in leaner individuals (P-interaction = 0.001), we saw no difference in the association of the insulin resistance score with T2D among BMI or waist strata (P-interaction > 0.31). While insulin resistance is often considered secondary to obesity, the association of the insulin resistance score with lower BMI and adiposity and with incident T2D even among individuals of normal weight highlights the role of insulin resistance and ectopic fat distribution in T2D, independently of body size.
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26.
  • Sluijs, Ivonne, et al. (författare)
  • A Mendelian randomization study of circulating uric acid and type 2 diabetes.
  • 2015
  • Ingår i: Diabetes. - American Diabetes Association Inc.. - 1939-327X. ; 64:8, s. 3028-3036
  • Tidskriftsartikel (refereegranskat)abstract
    • We aimed to investigate the causal effect of circulating uric acid concentrations on type 2 diabetes risk. A Mendelian randomization study was performed using a genetic score with 24 uric acid associated loci. We used data of the EPIC-InterAct case-cohort study, comprising 24,265 individuals of European ancestry from eight European countries. During a mean (SD) follow-up of 10 (4) years, 10,576 verified incident type 2 diabetes cases were ascertained. Higher uric acid associated with higher diabetes risk following adjustment for confounders, with a HR of 1.20 (95%CI: 1.11,1.30) per 59.48 µmol/L (1 mg/dL) uric acid. The genetic score raised uric acid by 17 µmol/L (95%CI: 15,18) per SD increase, and explained 4% of uric acid variation. Using the genetic score to estimate the unconfounded effect found that a 59.48 µmol/L higher uric acid concentration did not have a causal effect on diabetes (HR 1.01, 95%CI: 0.87,1.16). Including data from DIAGRAM consortium, increasing our dataset to 41,508 diabetes cases, the summary OR estimate was 0.99 (95%CI: 0.92, 1.06). In conclusion, our study does not support a causal effect of circulating uric acid on diabetes risk. Uric acid lowering therapies may therefore not be beneficial in reducing diabetes risk.
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27.
  • Sluijs, Ivonne, et al. (författare)
  • The amount and type of dairy product intake and incident type 2 diabetes : results from the EPIC-InterAct Study
  • 2012
  • Ingår i: American Journal of Clinical Nutrition. - 0002-9165. ; 96:2, s. 382-390
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Dairy product intake may be inversely associated with risk of type 2 diabetes, but the evidence is inconclusive for total dairy products and sparse for types of dairy products.Objective: The objective was to investigate the prospective association of total dairy products and different dairy subtypes with incidence of diabetes in populations with marked variation of intake of these food groups.Design: A nested case-cohort within 8 European countries of the European Prospective Investigation into Cancer and Nutrition Study (n = 340,234; 3.99 million person-years of follow-up) included a random subcohort (n = 16,835) and incident diabetes cases (n = 12,403). Baseline dairy product intake was assessed by using dietary questionnaires. Country-specific Prentice-weighted Cox regression HRs were calculated and pooled by using a random-effects meta-analysis.Results: Intake of total dairy products was not associated with diabetes (HR for the comparison of the highest with the lowest quintile of total dairy products: 1.01; 95% CI: 0.83, 1.34; P-trend = 0.92) in an analysis adjusted for age, sex, BMI, diabetes risk factors, education, and dietary factors. Of the dairy subtypes, cheese intake tended to have an inverse association with diabetes (HR: 0.88; 95% CI: 0.76, 1.02; P-trend = 0.01), and a higher combined intake of fermented dairy products (cheese, yogurt, and thick fermented milk) was inversely associated with diabetes (HR: 0.88; 95% CI: 0.78, 0.99; P-trend = 0.02) in adjusted analyses that compared extreme quintiles.Conclusions: This large prospective study found no association between total dairy product intake and diabetes risk. An inverse association of cheese intake and combined fermented dairy product intake with diabetes is suggested, which merits further study. Ant J Clin Nutr 2012;96:382-90.
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28.
  • Sluik, Diewertje, et al. (författare)
  • Lifestyle factors and mortality risk in individuals with diabetes mellitus: are the associations different from those in individuals without diabetes?
  • 2014
  • Ingår i: Diabetologia. - Springer. - 1432-0428. ; 57:1, s. 63-72
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis Thus far, it is unclear whether lifestyle recommendations for people with diabetes should be different from those for the general public. We investigated whether the associations between lifestyle factors and mortality risk differ between individuals with and without diabetes. Methods Within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort was formed of 6,384 persons with diabetes and 258,911 EPIC participants without known diabetes. Joint Cox proportional hazard regression models of people with and without diabetes were built for the following lifestyle factors in relation to overall mortality risk: BMI, waist/height ratio, 26 food groups, alcohol consumption, leisure-time physical activity, smoking. Likelihood ratio tests for heterogeneity assessed statistical differences in regression coefficients. Results Multivariable adjusted mortality risk among individuals with diabetes compared with those without was increased, with an HR of 1.62 (95% CI 1.51, 1.75). Intake of fruit, legumes, nuts, seeds, pasta, poultry and vegetable oil was related to a lower mortality risk, and intake of butter and margarine was related to an increased mortality risk. These associations were significantly different in magnitude from those in diabetes-free individuals, but directions were similar. No differences between people with and without diabetes were detected for the other lifestyle factors. Conclusions/interpretation Diabetes status did not substantially influence the associations between lifestyle and mortality risk. People with diabetes may benefit more from a healthy diet, but the directions of association were similar. Thus, our study suggests that lifestyle advice with respect to mortality for patients with diabetes should not differ from recommendations for the general population.
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29.
  • van Nielen, Monique, et al. (författare)
  • Dietary Protein Intake and Incidence of Type 2 Diabetes in Europe: The EPIC-InterAct Case-Cohort Study
  • 2014
  • Ingår i: Diabetes Care. - American Diabetes Association. - 1935-5548. ; 37:7, s. 1854-1862
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE The long-term association between dietary protein and type 2 diabetes incidence is uncertain. We aimed to investigate the association between total, animal, and plant protein intake and the incidence of type 2 diabetes. RESEARCH DESIGN AND METHODS The prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 individuals from eight European countries, with an average follow-up time of 12.0 years. Pooled country-specific hazard ratios (HRs) and 95% CI of prentice-weighted Cox regression analyses were used to estimate type 2 diabetes incidence according to protein intake. RESULTS After adjustment for important diabetes risk factors and dietary factors, the incidence of type 2 diabetes was higher in those with high intake of total protein (per 10 g: HR 1.06 [95% CI 1.02-1.09], P-trend < 0.001) and animal protein (per 10 g: 1.05 [1.02-1.08], P-trend = 0.001). Effect modification by sex (P < 0.001) and BMI among women (P < 0.001) was observed. Compared with the overall analyses, associations were stronger in women, more specifically obese women with a BMI > 30 kg/m(2) (per 10 g animal protein: 1.19 [1.09-1.32]), and nonsignificant in men. Plant protein intake was not associated with type 2 diabetes (per 10 g: 1.04 [0.93-1.16], P-trend = 0.098). CONCLUSIONS High total and animal protein intake was associated with a modest elevated risk of type 2 diabetes in a large cohort of European adults. In view of the rapidly increasing prevalence of type 2 diabetes, limiting iso-energetic diets high in dietary proteins, particularly from animal sources, should be considered.
30.
  • van Woudenbergh, Geertruida J., et al. (författare)
  • Tea Consumption and Incidence of Type 2 Diabetes in Europe: The EPIC-InterAct Case-Cohort Study
  • 2012
  • Ingår i: PLoS ONE. - Public Library of Science. - 1932-6203. ; 7:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In previous meta-analyses, tea consumption has been associated with lower incidence of type 2 diabetes. It is unclear, however, if tea is associated inversely over the entire range of intake. Therefore, we investigated the association between tea consumption and incidence of type 2 diabetes in a European population. Methodology/Principal Findings: The EPIC-InterAct case-cohort study was conducted in 26 centers in 8 European countries and consists of a total of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,835 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. Country-specific Hazard Ratios (HR) for incidence of type 2 diabetes were obtained after adjustment for lifestyle and dietary factors using a Cox regression adapted for a case-cohort design. Subsequently, country-specific HR were combined using a random effects meta-analysis. Tea consumption was studied as categorical variable (0, >0-<1, 1-<4, >= 4 cups/day). The dose-response of the association was further explored by restricted cubic spline regression. Country specific medians of tea consumption ranged from 0 cups/day in Spain to 4 cups/day in United Kingdom. Tea consumption was associated inversely with incidence of type 2 diabetes; the HR was 0.84 [95% CI 0.71, 1.00] when participants who drank >= 4 cups of tea per day were compared with non-drinkers (p(linear) (trend) = 0.04). Incidence of type 2 diabetes already tended to be lower with tea consumption of 1-<4 cups/day (HR = 0.93 [95% CI 0.81, 1.05]). Spline regression did not suggest a non-linear association (p(non-linearity) = 0.20). Conclusions/Significance: A linear inverse association was observed between tea consumption and incidence of type 2 diabetes. People who drink at least 4 cups of tea per day may have a 16% lower risk of developing type 2 diabetes than non-tea drinkers.
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