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1.
J Nutr ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33561273

RESUMO

BACKGROUND: Pancreatic cancer is a highly deadly disease with a poor prognosis. There is limited knowledge about prevention of the disease; thus, identification of risk factors is important to reduce the disease incidence. OBJECTIVE: The aim of the present study was to prospectively investigate associations between incidence of pancreatic cancer and whole-grain intake measured in 2 ways: as whole-grain product intake (g whole-grain products/d) and as whole-grain intake (grams of whole grains/d). Moreover, the intake of subgroups of these was also investigated: whole-grain products (rye bread, whole-grain bread, and oatmeal/muesli) and cereals (rye, wheat, and oats). METHODS: In total, 55,995 Danish adults aged 50-64 y, of whom 446 developed pancreatic cancer (17.5 y mean follow-up), were included in the study. Detailed information on daily intake of whole-grain products was available from a validated self-administered FFQ, and intake of whole-grain cereals (wheat, rye, and oats) was estimated using information from a 24-h dietary recall. The association between the whole-grain exposures and incidence of pancreatic cancer was investigated by Cox regression analyses adjusted for potential confounders. RESULTS: Total whole-grain product intake was associated with a 7% lower incidence of pancreatic cancer per serving (50 g/d) (HR: 0.93; 95% CI: 0.86, 1.00), and in the sex-specific analyses, an inverse association was found only in men. No association was found for total whole-grain intake (per 16-g serving size; HR: 0.96; 95% CI: 0.89, 1.03). When investigating specific whole-grain products and cereals individually, none were alone associated with lower incidence of pancreatic cancer. CONCLUSION: Our findings indicate that intake of whole grains is associated with lower risk of pancreatic cancer in middle-aged men. Consuming ample amounts of whole grains may prove beneficial in terms of lowering pancreatic cancer risk.

2.
Environ Int ; 150: 106428, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33571817

RESUMO

Cadmium exposure has been associated with cardiovascular disease. Cigarette smoking is a key source of cadmium exposure and thus a potential confounder in observational studies of environmental cadmium and cardiovascular disease that include tobacco smokers. We leveraged up to 20 years of follow-up in the Danish Diet, Cancer and Health cohort to test the hypothesis that cadmium exposure is associated with acute myocardial infarction (AMI) among people who never smoked. Between 1993 and 1997, 19,394 never-smoking participants (ages 50-64 years) were enrolled and provided a urine sample. From this sample, we randomly selected a subcohort of 600 males and 600 females. We identified 809 AMI cases occurring between baseline and the end of 2015 using the Danish National Patient Registry. We quantified cadmium, creatinine, and osmolality in baseline urine samples. Using an unweighted case-cohort approach, we estimated adjusted hazard ratios (aHR) for AMI in Cox proportional hazards models with age as the time axis. Participants had relatively low concentrations of urinary cadmium, as expected for never smokers (median = 0.20; 25th, 75th = 0.13, 0.32 µg cadmium/g creatinine). We did not find strong evidence to support an association between higher urinary cadmium and AMI when comparing the highest versus lowest quartile (aHR = 1.16; 95% CI: 0.86 - 1.56) and per IQR increment in cadmium concentration (aHR = 1.02; 95% CI: 0.93 - 1.12). Results were not materially different across strata defined by sex. Results were generally similar using creatinine or osmolality to account for differences in urine dilution. While cadmium exposure has been identified as a risk factor for cardiovascular disease, we did not find strong evidence that urinary cadmium at relatively low-levels is associated with AMI among people who have never smoked.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33619024

RESUMO

BACKGROUND: A growing body of evidence suggests that alterations of dietary fatty acid (FA) profiles are associated with colorectal cancer (CRC) risk. However, data from large-scale epidemiological studies using circulating FA measurements to objectively assess individual FA and FA categories are scarce. METHODS: To investigate the association between red blood cell (RBC) membrane FAs and risk of CRC in a case-control study nested within a large prospective cohort. After a median follow-up of 6.4 years, 1069 incident CRC cases were identified and matched to 1069 controls among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). The FA composition of RBC phospholipids (in mol%) was analyzed by gas chromatography, and their association with risk of CRC was estimated by multivariable adjusted conditional logistic regression models. RESULTS: After correction for multiple testing, subjects with higher concentrations of RBC stearic acid were at higher risk for CRC (OR=1.23; 95% CI=1.07-1.42, per 1 mol%). Conversely, CRC incidence decreased with increasing proportions of RBC n-3 PUFA, particularly eicosapentaenoic acid (0.75; 0.62-0.92, per 1 mol%). The findings for the n-6 PUFA arachidonic acid were inconsistent. CONCLUSIONS: The positive association between pre-diagnostic RBC stearic acid and CRC reflects putative differences in FA intake and metabolism between cancer cases and matched controls which deserve further investigation. The inverse relationship between EPA and CRC is in line with the repeatedly reported protective effect of fish consumption on CRC risk. IMPACT: These findings add to the evidence on CRC prevention.

4.
Br J Nutr ; : 1-21, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33509308

RESUMO

Intake of vegetables is recommended for the prevention of myocardial infarction (MI). However, vegetables make up a heterogeneous group, and subgroups of vegetables may be differentially associated with MI. The aim of this study was to examine replacement of potatoes with other vegetables or subgroups of other vegetables and the risk of MI. Substitutions between subgroups of other vegetables and risk of MI were also investigated. We followed 29,142 women and 26,029 men aged 50-64 years in the Danish Diet, Cancer and Health cohort. Diet was assessed at baseline by using a detailed validated FFQ. Hazards ratios (HR) with 95% CI for the incidence of MI were calculated using Cox proportional hazards regression. During 13.6 years of follow-up, 656 female and 1,694 male cases were identified. Among women, the adjusted HR for MI was 1.02 (95% CI: 0.93, 1.13) per 500 g/week replacement of potatoes with other vegetables. For vegetable subgroups, the HR was 0.93 (95% CI: 0.77, 1.13) for replacement of potatoes with fruiting vegetables and 0.91 (95% CI: 0.77, 1.07) for replacement of potatoes with other root vegetables. A higher intake of cabbage replacing other vegetable subgroups was associated with a statistically non-significant higher risk of MI. A similar pattern of associations was found when intake was expressed in kcal/week. Among men, the pattern of associations was overall found to be similar to that for women. This study supports food-based dietary guidelines recommending to consume a variety of vegetables from all subgroups.

5.
Eur J Clin Nutr ; 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514866

RESUMO

BACKGROUND: A high intake of marine n-3 polyunsaturated fatty acids (PUFAs) may lower the risk of coronary heart disease and ischemic stroke. The association between intake of marine n-3 PUFAs and development of peripheral artery disease (PAD), however, remains unexplored. We hypothesised that intake of marine n-3 PUFAs, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and the sum of EPA + DHA was associated with a lower risk of incident PAD. METHODS: We used data from the Danish Diet, Cancer and Health cohort and investigated the associations between intake of EPA, DHA and EPA + DHA and development of PAD. Information on intake of n-3 PUFAs was obtained through a validated food frequency questionnaire. Potential PAD cases were identified through linkage to the Danish National Patient Register and subsequently, all cases were validated. RESULTS: Data were available from 55,248 participants and during a median of 13.6 years of follow-up, 950 cases of PAD were identified. Multivariate Cox regression analyses with adjustments for established risk factors showed no statistically significant associations between intake of EPA (p = 0.255), DHA (p = 0.071) or EPA + DHA (p = 0.168) and the rate of incident PAD. CONCLUSIONS: We did not confirm our hypothesis that intake of EPA, DHA or EPA + DHA was associated with a lower risk of incident PAD.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33279777

RESUMO

BACKGROUND & AIMS: Colorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer (EPIC) cohort. METHODS: Scores reflecting adherence to the WCRF/AICR recommendations (scale 1-5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5,738 cancer-free EPIC participants with metabolomics data. Partial least squares regression was used to derive fatty acid and endogenous metabolite signatures of WCRF/AICR score in this group. In an independent set of 1,608 colorectal cancer cases and matched controls, odds ratios (OR) and 95% confidence intervals (CI) were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression. RESULTS: Higher WCRF/AICR scores were characterized by metabolic signatures of elevated odd-chain fatty acids, serine, glycine and specific phosphatidylcholines. Signatures were more strongly inversely associated with colorectal cancer risk (fatty acids: OR 0.51 per unit increase, 95% CI 0.29-0.90; endogenous metabolites: OR 0.62 per unit change, 95% CI 0.50-0.78) than the WCRF/AICR score (OR 0.93 per unit change, 95% CI 0.86-1.00) overall. Signature associations were stronger in male compared to female participants. CONCLUSIONS: Metabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.

7.
Am J Clin Nutr ; 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33300036

RESUMO

The advantage of using specified substitution analysis in nutritional epidemiology has been clearly demonstrated in studies of macronutrient intake and disease risk. However, the method has not been widely applied in studies of food intake. The aim of this article is to describe and compare the interpretation and application of different food substitution models in epidemiologic studies on diet and disease development. Both theoretically and in the context of a specific example, we discuss methodologic issues to be considered, including modeling of food substitutions using diet at a single time point or at multiple time points (focusing on dietary changes), choice of substitution unit, adjustment for total energy intake, and adjustment for confounding. We argue that specified food substitution analyses can be used to identify optimal food composition of the diet and that these analyses are thus highly relevant to inform public health policy decision makers.

8.
Diabetes Care ; 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33303636

RESUMO

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 (P = 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.

9.
Br J Nutr ; : 1-15, 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33357247

RESUMO

The objective was to investigate the effects of substitution (SUB) dietary guidelines (DG) targeted at the prevention of IHD on dietary intake and IHD risk factors in Danish adults with minimum one self-assessed IHD risk factor. A 6-month single-blinded parallel randomised controlled trial with a follow-up at month 12 included 219 subjects (median age 51 years, 59 % female, 73 % overweight or obese) randomised into an SUB DG, an official (OFF) DG or a control group following their habitual diet (HAB). Participants in the DG intervention groups received bi-weekly reminders of their DG and recipes for dishes and the HAB group received a greeting. Dietary intake and fasting blood, anthropometric and blood pressure measurements were obtained at baseline, month 6 and month 12. Linear regression analyses were applied. At month 6, when compared with the HAB, the SUB had a greater impact on the extent of dietary changes with increased intake of whole grains, dietary fibre and low fibre vegetables compared with the OFF DG, and both DG groups had similar decreased percentage of energy (E%) intake from SFA. The extent of dietary changes was similar at month 12. No overall significant changes from baseline were found in blood pressure, anthropometrics and IHD risk markers. In conclusion, both SUB and OFF DG resulted in cardioprotective dietary changes. However, neither the SUB nor the OFF DG resulted in any overall effects on the selected intermediate risk factors for IHD.

10.
Sci Data ; 7(1): 393, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-33188205

RESUMO

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.

11.
Eur J Clin Nutr ; 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33191404

RESUMO

BACKGROUND/OBJECTIVES: We evaluated the association between adherence to the 2013 Danish dietary guidelines and the risk of type 2 diabetes (T2D) in a Danish cohort. SUBJECTS/METHODS: We used data from the Danish Diet, Cancer, and Health cohort. Participants aged 50-64 years were included from 1993-1997. Information on diet and covariates was collected at baseline using questionnaires and physical assessments. A diet index was developed to assess adherence to the Danish dietary guidelines. T2D cases were identified using the Danish National Diabetes Register. Cox proportional hazards regression was used to estimate hazard ratios (HR), and the pseudo-observation method was used to estimate risk differences, and 95% confidence intervals (CI). RESULTS: A total of 54,305 subject were included. During a median follow-up of 15 years, 7136 participants were diagnosed with T2D. After multivariable adjustment, the HR for high versus low adherence to the index was 0.57 (95 % CI: 0.48, 0.69) in men, and 0.71 (95% CI: 0.60, 0.83) in women. Compared with the lowest adherence to the index, high adherence was associated with a 6.58% (95% CI: -8.69; -4.47%) or 3.17% (95% CI: -4.90, -1.44%) lower risk of T2D in men and women, respectively. CONCLUSIONS: High adherence to the Danish food-based dietary guidelines was associated with lower risk of T2D in a Danish cohort, both on a relative and an absolute scale. Shifting from low to high adherence to the dietary guidelines may provide public health benefit.

12.
Diabetes Care ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203707

RESUMO

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 (P < 5 × 10-8), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. 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 FADS1 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.

13.
Am J Clin Nutr ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33094800

RESUMO

BACKGROUND: Greater consumption of red meat has been associated with a higher risk of type 2 diabetes mellitus (T2DM). A decreased intake of red meat and simultaneous increased intake of other high-protein foods may be associated with a lower risk of T2DM. These analyses of specific food replacements for red meat may provide more accurate dietary advice. OBJECTIVE: We examined the association between a decrease in intake of red meat accompanied by an increase in other major dietary protein sources and risk of T2DM. METHODS: We prospectively followed 27,634 males in the Health Professionals Follow-up Study, 46,023 females in the Nurses' Health Study, and 75,196 females in the Nurses' Health Study II. Diet was assessed by a validated FFQ and updated every 4 y. Cox proportional hazards models adjusted for T2DM risk factors were used to model the food replacements. We calculated HRs and 95% CIs for the T2DM risk associated with replacements of 1 daily serving of red meat with another protein source. RESULTS: During 2,113,245 person-years of follow-up, we identified 8763 incident T2DM cases from 1990 to 2013. In the pooled analyses, a decrease in total red meat intake during a 4-y period replaced with another common protein food was associated with a lower risk of T2DM in the subsequent 4-y period. The HR (95% CI) per 1 serving/d was 0.82 (0.75, 0.90) for poultry, 0.87 (0.77, 0.98) for seafood, 0.82 (0.78, 0.86) for low-fat dairy, 0.82 (0.77, 0.86) for high-fat dairy, 0.90 (0.81, 0.99) for eggs, 0.89 (0.82, 0.98) for legumes, and 0.83 (0.78, 0.89) for nuts. The associations were present for both unprocessed and processed red meat, although stronger for the replacement of processed red meat. CONCLUSIONS: Replacing red meat consumption with other protein sources was associated with a lower risk of T2DM.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33082206

RESUMO

BACKGROUND: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation. METHODS: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively. RESULTS: Higher sRAGE concentrations were inversely associated with colorectal cancer (ORQ5vs.Q1, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (ORQ5vs.Q1, 1.00; 95% CI, 0.68-1.48; P heterogeneity for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99). CONCLUSIONS: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within ADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk. IMPACT: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.

15.
Int J Cancer ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33038275

RESUMO

Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (±0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.

16.
PLoS Med ; 17(10): e1003394, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33064751

RESUMO

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.

17.
Am J Clin Nutr ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021645

RESUMO

BACKGROUND: Polyphenols are natural compounds with anticarcinogenic properties in cellular and animal models, but epidemiological evidence determining the associations of these compounds with thyroid cancer (TC) is lacking. OBJECTIVES: The aim of this study was to evaluate the relations between blood concentrations of 36 polyphenols and TC risk in EPIC (the European Prospective Investigation into Cancer and Nutrition). METHODS: A nested case-control study was conducted on 273 female cases (210 papillary, 45 follicular, and 18 not otherwise specified TC tumors) and 512 strictly matched controls. Blood polyphenol concentrations were analyzed by HPLC coupled to tandem MS after enzymatic hydrolysis. RESULTS: Using multivariable-adjusted conditional logistic regression models, caffeic acid (ORlog2: 0.55; 95% CI: 0.33, 0.93) and its dehydrogenated metabolite, 3,4-dihydroxyphenylpropionic acid (ORlog2: 0.84; 95% CI: 0.71, 0.99), were inversely associated with differentiated TC risk. Similar results were observed for papillary TC, but not for follicular TC. Ferulic acid was also inversely associated only with papillary TC (ORlog2: 0.68; 95% CI: 0.51, 0.91). However, none of these relations was significant after Bonferroni correction for multiple testing. No association was observed for any of the remaining polyphenols with total differentiated, papillary, or follicular TC. CONCLUSIONS: Blood polyphenol concentrations were mostly not associated with differentiated TC risk in women, although our study raises the possibility that high blood concentrations of caffeic, 3,4-dihydroxyphenylpropionic, and ferulic acids may be related to a lower papillary TC risk.

18.
Diabetes Care ; 43(11): 2660-2667, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32868270

RESUMO

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.

19.
BMJ ; 370: m3173, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938660

RESUMO

OBJECTIVE: To determine if the Food Standards Agency nutrient profiling system (FSAm-NPS), which grades the nutritional quality of food products and is used to derive the Nutri-Score front-of-packet label to guide consumers towards healthier food choices, is associated with mortality. DESIGN: Population based cohort study. SETTING: European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from 23 centres in 10 European countries. PARTICIPANTS: 521 324 adults; at recruitment, country specific and validated dietary questionnaires were used to assess their usual dietary intakes. A FSAm-NPS score was calculated for each food item per 100 g content of energy, sugars, saturated fatty acids, sodium, fibre, and protein, and of fruit, vegetables, legumes, and nuts. The FSAm-NPS dietary index was calculated for each participant as an energy weighted mean of the FSAm-NPS score of all foods consumed. The higher the score the lower the overall nutritional quality of the diet. MAIN OUTCOME MEASURE: Associations between the FSAm-NPS dietary index score and mortality, assessed using multivariable adjusted Cox proportional hazards regression models. RESULTS: After exclusions, 501 594 adults (median follow-up 17.2 years, 8 162 730 person years) were included in the analyses. Those with a higher FSAm-NPS dietary index score (highest versus lowest fifth) showed an increased risk of all cause mortality (n=53 112 events from non-external causes; hazard ratio 1.07, 95% confidence interval 1.03 to 1.10, P<0.001 for trend) and mortality from cancer (1.08, 1.03 to 1.13, P<0.001 for trend) and diseases of the circulatory (1.04, 0.98 to 1.11, P=0.06 for trend), respiratory (1.39, 1.22 to 1.59, P<0.001), and digestive (1.22, 1.02 to 1.45, P=0.03 for trend) systems. The age standardised absolute rates for all cause mortality per 10 000 persons over 10 years were 760 (men=1237; women=563) for those in the highest fifth of the FSAm-NPS dietary index score and 661 (men=1008; women=518) for those in the lowest fifth. CONCLUSIONS: In this large multinational European cohort, consuming foods with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher mortality for all causes and for cancer and diseases of the circulatory, respiratory, and digestive systems, supporting the relevance of FSAm-NPS to characterise healthier food choices in the context of public health policies (eg, the Nutri-Score) for European populations. This is important considering ongoing discussions about the potential implementation of a unique nutrition labelling system at the European Union level.


Assuntos
Rotulagem de Alimentos , Mortalidade , Valor Nutritivo , Adulto , Estudos de Coortes , Europa (Continente) , Feminino , Preferências Alimentares , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Modelos de Riscos Proporcionais , Inquéritos e Questionários
20.
Sci Rep ; 10(1): 14541, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883969

RESUMO

Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI < 18.5 kg/m2) or obese (BMI ≥ 30 kg/m2) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.

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