Objective and subjective sleep measures are associated with HbA1c and insulin sensitivity in the general population: Findings from the ORISCAV-LUX-2 study.

AIM: To analyze the association of objective and subjective sleep measures with HbA1c and insulin sensitivity in the general population. METHODS: Using a cross-sectional design, data from 1028 participants in the ORISCAV-LUX-2 study from the general population in Luxembourg were analyzed. Objective sleep measures were assessed using accelerometers whereas subjective measures were assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Sleep measures were defined as predictors, while HbA1c and quantitative insulin sensitivity check index (QUICKI) scores were considered outcomes. Linear and spline regression models were fitted by progressively adjusting for demographic and lifestyle variables in the total sample population as well as by stratified analyses using gender, obesity status, depressive symptoms and diabetes status. RESULTS: In fully adjusted models, total and deep sleep durations were associated with lower HbA1c (mmol/mol) levels, whereas sleep coefficients of variation (%) and poor sleep efficiency, as measured by PSQI scores (units), were associated with higher HbA1c levels. In stratified models, such associations were observed mainly in men, and in subjects who had depressive symptoms, were overweight and no diabetes. In addition, total sleep, deep sleep, coefficients of variation and poor sleep efficiency as measured by PSQI revealed non-linear associations. Similarly, greater insulin sensitivity was associated with longer total sleep time and with PSQI-6 (use of sleep medication). CONCLUSION: Associations were more frequently observed between sleep characteristics and glycaemic control with the use of objective sleep measures. Also, such associations varied within subgroups of the population. Our results highlight the relevance of measuring sleep patterns as key factors in the prevention of diabetes.

Design of a prospective, longitudinal cohort of people living with type 1 diabetes exploring factors associated with the residual cardiovascular risk and other diabetes-related complications: The SFDT1 study.

Type 1 diabetes mellitus (T1DM) is associated with a high risk of cardiovascular (CV) complications, even after controlling for traditional CV risk factors. Therefore, determinants of the residual increased CV morbidity and mortality remain to be discovered. This prospective cohort of people living with T1DM in France (SFDT1) will include adults and children aged over six years living with T1DM, recruited throughout metropolitan France and overseas French departments and territories. The primary objective is to better understand the parameters associated with CV complications in T1DM. Clinical data and biobank samples will be collected during routine visits every three years. Data from connected tools, including continuous glucose monitoring, will be available during the 10-year active follow-up. Patient-reported outcomes, psychological and socioeconomic information will also be collected either at visits or through web questionnaires accessible via the internet. Additionally, access to the national health data system (Health Data Hub) will provide information on healthcare and a passive 20-year medico-administrative follow-up. Using Health Data Hub, SFDT1 participants will be compared to non-diabetic individuals matched on age, gender, and residency area. The cohort is sponsored by the French-speaking Foundation for Diabetes Research (FFRD) and aims to include 15,000 participants.

[Interest of a geostatistical approach to analyze the geographical disparities in human papillomavirus vaccine coverage in France]. / Intérêt d'une approche géostatistique pour analyser les disparités géographiques de la couverture vaccinale contre les papillomavirus humains en France.

BACKGROUND: The use of geostatistical methods remains rare in health studies. In order to assess the usefulness of the geostatistical approach in epidemiology, we chose to apply these methods to the vaccination coverage rate (VCR) against human papillomavirus (HPV) in France. Indeed, HPV vaccine coverage remains low in France and geographical disparities are sizable. The objective of this study was to identify the socioecological factors that may explain these geographical variations. METHODS: Sociological, economic and behavioral data for 2016 have been gathered (demographics and public health database, web and social networks) and were correlated with the HPV VCR vaccine coverage over the French territory. Homogeneous geographical areas defined by strong correlations for groups of variables were selected. In each homogeneous area, principal component analysis was performed and a geostatistical approach provided an estimate predicting vaccine coverage at a given scale. RESULTS: HPV VCR spatial variations in France cannot be fully explained by a single model. In urban areas, a low rate of HPV VCR is preferentially associated with unfavorable socioeconomic factors (poverty, unemployment, immigration). In rural areas, HPV VCR is preferentially associated with sociocultural factors (socio-professional categories, education level, interest in alternative medicines the anti-vaccine movement). Two secondary geographical areas were defined: the Île-de-France region and 12 departments in northeastern France. In the Île-de-France region, the association with the economic factors one again appears as in urban areas in general. The northeasteran departments represent a particular case insofar as HPV VCR is relatively high, notwithstanding economic poverty indicators. CONCLUSION: Geostatistical modeling successfully identifies new potential explanations for HPV VCR geographical disparities in France. These results could help to adapt or develop future vaccination programs in specific areas by taking into account the sociological, economic and behavioral characteristics of their populations.

Increased risk of type 2 diabetes in antidepressant users: evidence from a 6-year longitudinal study in the E3N cohort.

AIM: To examine the association between antidepressant medication use and the risk of type 2 diabetes. METHODS: Data were obtained from the E3N study (Étude Épidémiologique de Femmes de la Mutuelle Générale de l'Éducation Nationale), a French cohort study initiated in 1990, with questionnaire-based follow-up every 2 or 3 years. Exposure to antidepressants was obtained from drug reimbursement files available from 2004 onwards, and individually matched with questionnaire data. Cases of type 2 diabetes were identified from drug reimbursements. Cox proportional-hazard regression models were used, with drug exposure considered as a time-varying parameter. RESULTS: Of the 63 999 women who were free of drug-treated type 2 diabetes at baseline in 2005, 1124 developed type 2 diabetes over the 6-year follow-up. Current use of antidepressants was associated with an increased risk of type 2 diabetes [hazard ratio 1.34 (95% CI 1.12, 1.61)] compared to non-users. When the different types of antidepressants were considered, women who currently used selective serotonin reuptake inhibitors, imipramine-type, 'other' or 'mixed' antidepressants had a 1.25-fold (95% CI 0.99, 1.57), 1.66-fold (95% CI 1.12, 2.46), 1.35-fold (95% CI 1.00, 1.84) and 1.82-fold (95% CI 0.85, 3.86) increase in risk of type 2 diabetes compared to non-users, respectively. CONCLUSION: Our study suggests a positive association between antidepressant use and the risk of type 2 diabetes among women. If this association is confirmed, screening and surveillance of glucose levels should be considered in the context of antidepressant therapy. Further studies assessing the underlying mechanisms of this association are needed. (ClinicalTrials.gov identifier: NCT03285230).

Dietary intake of advanced glycation end products (AGEs) and changes in body weight in European adults.

PURPOSE: Advanced glycation end products (AGEs) can be formed in foods by the reaction of reducing sugars with proteins, and have been shown to induce insulin resistance and obesity in experimental studies. We examined the association between dietary AGEs intake and changes in body weight in adults over an average of 5 years of follow-up. METHODS: A total of 255,170 participants aged 25-70 years were recruited in ten European countries (1992-2000) in the PANACEA study (Physical Activity, Nutrition, Alcohol, Cessation of smoking, Eating out of home in relation to Anthropometry), a sub-cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition). Body weight was measured at recruitment and self-reported between 2 and 11 years later depending on the study center. A reference database for AGEs was used containing UPLC-MS/MS-measured Nε-(carboxymethyl)-lysine (CML), Nε-(1-carboxyethyl)-lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) in 200 common European foods. This reference database was matched to foods and decomposed recipes obtained from country-specific validated dietary questionnaires in EPIC and intake levels of CEL, CML, and MG-H1 were estimated. Associations between dietary AGEs intake and body weight change were estimated separately for each of the three AGEs using multilevel mixed linear regression models with center as random effect and dietary AGEs intake and relevant confounders as fixed effects. RESULTS: A one-SD increment in CEL intake was associated with 0.111 kg (95% CI 0.087-0.135) additional weight gain over 5 years. The corresponding additional weight gain for CML and MG-H1 was 0.065 kg (0.041-0.089) and 0.034 kg (0.012, 0.057), respectively. The top six food groups contributing to AGEs intake, with varying proportions across the AGEs, were cereals/cereal products, meat/processed meat, cakes/biscuits, dairy, sugar and confectionary, and fish/shellfish. CONCLUSION: In this study of European adults, higher intakes of AGEs were associated with marginally greater weight gain over an average of 5 years of follow-up.

Socioeconomic inequalities and type 2 diabetes complications: A systematic review.

BACKGROUND AND OBJECTIVES: A socioeconomic gradient related to type 2 diabetes (T2D) prevalence has been demonstrated in high-income countries. However, there is no evidence of such a socioeconomic gradient regarding diabetes complications. Thus, the aim of this systematic review was to collect data on risk of complications according to socioeconomic status in patients with T2D. METHODS: PubMed and EMBASE were searched for English-language observational studies evaluating the prevalence or incidence of micro- and macrovascular complications according to individual and geographical socioeconomic status (SES). Observational studies reporting the prevalence and risk of micro- and macrovascular diabetes complications, according to an individual or geographical index of deprivation, were selected, and estimated crude and adjusted risks for each complication were reported. RESULTS: Among the 28 included studies, most described a clear relationship between SES and diabetes complications, especially retinopathy (in 9 of 14 studies) and cardiopathy (in 8 of 9 studies). Both individual and area-based low SES was associated with an increased risk of complications. However, very few studies adjusted their analyses according to HbA1c level. CONCLUSION: Evaluation of SES is necessary for every T2D patient, as it appears to be a risk factor for diabetes complications. However, the available studies are insufficient for gradation of the impact of low socioeconomic level on each of these complications. Regardless, strategies for the improved screening, follow-up and care of high-risk patients should now be implemented.

Digital diabetes: Perspectives for diabetes prevention, management and research.

Digital medicine, digital research and artificial intelligence (AI) have the power to transform the field of diabetes with continuous and no-burden remote monitoring of patients' symptoms, physiological data, behaviours, and social and environmental contexts through the use of wearables, sensors and smartphone technologies. Moreover, data generated online and by digital technologies - which the authors suggest be grouped under the term 'digitosome' - constitute, through the quantity and variety of information they represent, a powerful potential for identifying new digital markers and patterns of risk that, ultimately, when combined with clinical data, can improve diabetes management and quality of life, and also prevent diabetes-related complications. Moving from a world in which patients are characterized by only a few recent measurements of fasting glucose levels and glycated haemoglobin to a world where patients, healthcare professionals and research scientists can consider various key parameters at thousands of time points simultaneously will profoundly change the way diabetes is prevented, managed and characterized in patients living with diabetes, as well as how it is scientifically researched. Indeed, the present review looks at how the digitization of diabetes can impact all fields of diabetes - its prevention, management, technology and research - and how it can complement, but not replace, what is usually done in traditional clinical settings. Such a profound shift is a genuine game changer that should be embraced by all, as it can provide solid research results transferable to patients, improve general health literacy, and provide tools to facilitate the everyday decision-making process by both healthcare professionals and patients living with diabetes.

Determinants of 20-year non-progression to Type 2 diabetes in women at very high risk: the E3N cohort study.

AIMS: To identify the most important determinants associated with not developing Type 2 diabetes in women considered to be at very high risk. METHODS: Between 1995 and 2014, we followed 402 women from the E3N cohort study who were considered to be at very high risk of Type 2 diabetes based on the D.E.S.I.R. score. We then computed a classification and regression tree model to identify, among a large set of risk factors, the top risk factors associated with not having Type 2 diabetes at the end of the follow-up. RESULTS: During follow-up, 117 women (29%) were diagnosed with Type 2 diabetes, while 285 (71%) were still free of the disease in 2014. A low Western dietary pattern score was the top characteristic associated with not developing Type 2 diabetes, as only 20% of the women at very high risk in the E3N study with that characteristic developed Type 2 diabetes (compared with 29% overall). In women with a moderate or high Western dietary pattern score, the most important characteristic associated with not developing Type 2 diabetes was a high total dietary antioxidant capacity, as only 26% of these women ultimately developed Type 2 diabetes. CONCLUSIONS: We showed that the top characteristic associated with not developing Type 2 diabetes, despite being at very high risk, was a healthy diet, characterized by limiting Western dietary habits, but with a high intake of antioxidant-rich foods. This underscores the importance of diet in the prevention of Type 2 diabetes in people at high risk.

Transmission of Type 2 diabetes to sons and daughters: the D.E.S.I.R. cohort.

AIMS: To document the family transmission of Type 2 diabetes to men and women. METHOD: The French D.E.S.I.R. cohort followed men and women over 9 years, with 3-yearly testing for incident Type 2 diabetes. First- and/or second-degree family histories of diabetes were available for 2187 men and 2282 women. Age-adjusted hazard ratios were estimated for various family members and groupings of family members, as well as for a genetic diabetes risk score, based on 65 diabetes-associated loci. RESULTS: Over 9 years, 136 men and 63 women had incident Type 2 diabetes. The hazard ratios for diabetes associated with having a first-degree family member with diabetes (parents, siblings, children) differed between men [1.21 (95% CI 0.80, 1.85)] and women [3.02 (95% CI 1.83, 4.99); Pinteraction =0.006]. The genetic risk score was predictive of diabetes in both men and women, with similar hazard ratios 1.10 (95% CI 1.06, 1.15) and 1.08 (95% CI 1.02, 1.14) respectively, for each additional at-risk allele. In women, the risk associated with having a family member with diabetes persisted after adjusting for the genetic score. CONCLUSION: Women with a family history of diabetes (paternal or maternal) were at risk of developing Type 2 diabetes and this risk was independent of a genetic score; in contrast, for men, there was no association. Diabetes screening and prevention may need to more specifically target women with diabetes in their family, but further studies are required as the number of people with diabetes in this study was small.

Meal patterns across ten European countries - results from the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study.

OBJECTIVE: To characterize meal patterns across ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study. DESIGN: Cross-sectional study utilizing dietary data collected through a standardized 24 h diet recall during 1995-2000. Eleven predefined intake occasions across a 24 h period were assessed during the interview. In the present descriptive report, meal patterns were analysed in terms of daily number of intake occasions, the proportion reporting each intake occasion and the energy contributions from each intake occasion. SETTING: Twenty-seven centres across ten European countries. SUBJECTS: Women (64 %) and men (36 %) aged 35-74 years (n 36 020). RESULTS: Pronounced differences in meal patterns emerged both across centres within the same country and across different countries, with a trend for fewer intake occasions per day in Mediterranean countries compared with central and northern Europe. Differences were also found for daily energy intake provided by lunch, with 38-43 % for women and 41-45 % for men within Mediterranean countries compared with 16-27 % for women and 20-26 % for men in central and northern European countries. Likewise, a south-north gradient was found for daily energy intake from snacks, with 13-20 % (women) and 10-17 % (men) in Mediterranean countries compared with 24-34 % (women) and 23-35 % (men) in central/northern Europe. CONCLUSIONS: We found distinct differences in meal patterns with marked diversity for intake frequency and lunch and snack consumption between Mediterranean and central/northern European countries. Monitoring of meal patterns across various cultures and populations could provide critical context to the research efforts to characterize relationships between dietary intake and health.

Functional gastrointestinal disorders and incidence of type 2 diabetes: Evidence from the E3N-EPIC cohort study.

OBJECTIVE: Functional gastrointestinal disorders (FGID) such as diarrhoea and constipation can reflect intestinal dysfunction, especially with regard to intestinal microbiota, which, in turn, have been associated with chronic conditions, including obesity and insulin resistance. However, little is known of the association between FGID and type 2 diabetes (T2D) risk. DESIGN AND METHODS: This analysis aimed to determine the influence of diarrhoea, constipation and alternating bouts of diarrhoea/constipation on T2D risk in 62,683 women from the prospective E3N-EPIC cohort. RESULTS: A total of 1795 T2D cases were recorded during follow-up. Compared with women who had normal gastrointestinal transits, women with chronic diarrhoea or alternating diarrhoea/constipation were at increased risk of T2D (HR: 1.29, 95% CI: 1.00-1.65 vs. HR: 1.32, 95% CI: 1.15-1.52, respectively), whereas women with constipation had a decreased risk (HR: 0.67, 95% CI: 0.57-0.78). There was no interaction between FGID and body mass index for risk of T2D. Also, these associations were independent of dietary habits such as coffee, fruit and vegetable consumption, and even of the use of laxatives and psychotropic drugs. CONCLUSION: The present analysis showed, for the first time, a limited association between FGID and T2D risk in a large prospective cohort, and supports the hypothesis of a relationship between gastrointestinal function and diabetes. The presence of gastrointestinal transit disorders may assist in screening for subjects at higher risk of diabetes beyond the conventional risk factors.

[Prognostic value of VZV PCR in cerebrospinal fluid in neurological manifestations of varicella]. / Manifestations neurologiques associées à la varicelle : apport de l'amplification génique dans le liquide céphalo-rachidien.

Varicella-zoster virus (VZV) is, like other alphaherpes viruses, neurotropic. Of the admissions to hospital for varicella, 7.6-25% are due to neurologic manifestations. Most of the time, the concomitant skin lesions facilitate the diagnosis. The justification of qualitative PCR (polymerase chain reaction) for VZV DNA in cerebrospinal fluid in the management of these patients is not clear. The aim of this study was to evaluate the prognostic value of qualitative PCR for VZV DNA in cerebrospinal fluid and to assess its impact on patient management. We conducted a retrospective monocentric study in Versailles Hospital (France). It included every child admitted for neurologic manifestations associated with varicella and compared the patients with positive PCR for VZV DNA to those with a negative PCR in the cerebrospinal fluid. Seven patients with positive PCR and 16 patients with negative PCR were included. The median age of the children included was 3 years (range, 1.6-12 years) and 2 years (range, 0.6-5 years), respectively. In the positive PCR group, 86% of the children had fever on first examination and the average time between the onset of skin lesions and neurological signs was +1.28 days (range, -2 to +5 days). In comparison, in the negative PCR group, 81% of the children had fever and the average time delay was +1.75 days (-2 to +7 days). There was no significant difference in terms of length of hospitalization; 3 days (range, 0-6 days) and 3 days (range, 2-7 days), respectively. All patients discharged from our department went home. In addition, there was no significant difference between the two groups in terms of treatment with acyclovir; two children (28.5%) were treated in the positive PCR group versus four (25%) in the negative PCR group. Our study showed no prognostic value for qualitative PCR for VZV DNA in the cerebrospinal fluid of patients with neurologic manifestations of varicella. Therefore, its relevance can be questioned in clinical practice. However, in case of encephalitis and meningitis during primary infection with VZV, quantitative PCR for VZV DNA might have a prognostic value and therefore requires further study.

Diabetes and onset of natural menopause: results from the European Prospective Investigation into Cancer and Nutrition.

STUDY QUESTION: Do women who have diabetes before menopause have their menopause at an earlier age compared with women without diabetes? SUMMARY ANSWER: Although there was no overall association between diabetes and age at menopause, our study suggests that early-onset diabetes may accelerate menopause. WHAT IS KNOWN ALREADY: Today, more women of childbearing age are being diagnosed with diabetes, but little is known about the impact of diabetes on reproductive health. STUDY DESIGN, SIZE, DURATION: We investigated the impact of diabetes on age at natural menopause (ANM) in 258 898 women from the European Prospective Investigation into Cancer and Nutrition (EPIC), enrolled between 1992 and 2000. PARTICIPANTS/MATERIALS, SETTING, METHODS: Determinant and outcome information was obtained through questionnaires. Time-dependent Cox regression analyses were used to estimate the associations of diabetes and age at diabetes diagnosis with ANM, stratified by center and adjusted for age, smoking, reproductive and diabetes risk factors and with age from birth to menopause or censoring as the underlying time scale. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, no association between diabetes and ANM was found (hazard ratio (HR) = 0.94; 95% confidence interval (CI) 0.89-1.01). However, women with diabetes before the age of 20 years had an earlier menopause (10-20 years: HR = 1.43; 95% CI 1.02-2.01, <10 years: HR = 1.59; 95% CI 1.03-2.43) compared with non-diabetic women, whereas women with diabetes at age 50 years and older had a later menopause (HR = 0.81; 95% CI 0.70-0.95). None of the other age groups were associated with ANM. LIMITATIONS, REASONS FOR CAUTION: Strengths of the study include the large sample size and the broad set of potential confounders measured. However, results may have been underestimated due to survival bias. We cannot be sure about the sequence of the events in women with a late age at diabetes, as both events then occur in a short period. We could not distinguish between type 1 and type 2 diabetes. WIDER IMPLICATIONS OF THE FINDINGS: Based on the literature, an accelerating effect of early-onset diabetes on ANM might be plausible. A delaying effect of late-onset diabetes on ANM has not been reported before, and is not in agreement with recent studies suggesting the opposite association. STUDY FUNDING/COMPETING INTERESTS: The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ) and Federal Ministry of Education and Research (BMMF) (Germany); Ministry of Health and Social Solidarity, Stavros Niarchos Foundation and Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC) and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). None of the authors reported a conflict of interest.

Healthy lifestyle index and risk of gastric adenocarcinoma in the EPIC cohort study.

Several modifiable lifestyle factors, including smoking, alcohol, certain dietary factors and weight are independently associated with gastric cancer (GC); however, their combined impact on GC risk is unknown. We constructed a healthy lifestyle index to investigate the joint influence of these behaviors on GC risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The analysis included 461,550 participants (662 first incident GC cases) with a mean follow-up of 11.4 years. A healthy lifestyle index was constructed, assigning 1 point for each healthy behavior related to smoking status, alcohol consumption and diet quality (represented by the Mediterranean diet) for assessing overall GC and also body mass index for cardia GC and 0 points otherwise. Risk of GC was calculated using Cox proportional hazards regression models while adjusting for relevant confounders. The highest versus lowest score in the healthy lifestyle index was associated with a significant lower risk of GC, by 51% overall (HR 0.49 95% CI 0.35, 0.70), by 77% for cardia GC (HR 0.23 95% CI 0.08, 0.68) and by 47% for noncardia GC (HR 0.53 (95% CI 0.32, 0.87), p-trends<0.001. Population attributable risk calculations showed that 18.8% of all GC and 62.4% of cardia GC cases could have been prevented if participants in this population had followed the healthy lifestyle behaviors of this index. Adopting several healthy lifestyle behaviors including not smoking, limiting alcohol consumption, eating a healthy diet and maintaining a normal weight is associated with a large decreased risk of GC.

Consumption of fatty foods and incident type 2 diabetes in populations from eight European countries.

BACKGROUND/OBJECTIVES: Diets high in saturated and trans fat and low in unsaturated fat may increase type 2 diabetes (T2D) risk, but studies on foods high in fat per unit weight are sparse. We assessed whether the intake of vegetable oil, butter, margarine, nuts and seeds and cakes and cookies is related to incident T2D. SUBJECTS/METHODS: A case-cohort study was conducted, nested within eight countries of the European Prospective Investigation into Cancer (EPIC), with 12,403 incident T2D cases and a subcohort of 16,835 people, identified from a cohort of 340,234 people. Diet was assessed at baseline (1991-1999) by country-specific questionnaires. Country-specific hazard ratios (HRs) across four categories of fatty foods (nonconsumers and tertiles among consumers) were combined with random-effects meta-analysis. RESULTS: After adjustment not including body mass index (BMI), nonconsumers of butter, nuts and seeds and cakes and cookies were at higher T2D risk compared with the middle tertile of consumption. Among consumers, cakes and cookies were inversely related to T2D (HRs across increasing tertiles 1.14, 1.00 and 0.92, respectively; P-trend <0.0001). All these associations attenuated upon adjustment for BMI, except the higher risk of nonconsumers of cakes and cookies (HR 1.57). Higher consumption of margarine became positively associated after BMI adjustment (HRs across increasing consumption tertiles: 0.93, 1.00 and 1.12; P-trend 0.03). Within consumers, vegetable oil, butter and nuts and seeds were unrelated to T2D. CONCLUSIONS: Fatty foods were generally not associated with T2D, apart from weak positive association for margarine. The higher risk among nonconsumers of cakes and cookies needs further explanation.

Dietary folate intake and breast cancer risk: European prospective investigation into cancer and nutrition.

BACKGROUND: There is limited evidence on the association between dietary folate intake and the risk of breast cancer (BC) by hormone receptor expression in the tumors. We investigated the relationship between dietary folate and BC risk using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: A total of 367993 women age 35 to 70 years were recruited in 10 European countries. During a median follow-up of 11.5 years, 11575 women with BC were identified. Dietary folate intake was estimated from country-specific dietary questionnaires. Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk. BC tumors were classified by receptor status. Subgroup analyses were performed by menopausal status and alcohol intake. Intake of other B vitamins was considered. All statistical tests were two-sided. RESULTS: A borderline inverse association was observed between dietary folate and BC risk (hazard ratio comparing top vs bottom quintile [HRQ5-Q1] = 0.92, 95% CI = 0.83 to 1.01, P trend = .037). In premenopausal women, we observed a statistically significant trend towards lower risk in estrogen receptor-negative BC (HRQ5-Q1 = 0.66, 95% CI = 0.45 to 0.96, P trend = .042) and progesterone receptor-negative BC (HRQ5-Q1 = 0.70, 95% CI = 0.51 to 0.97, P trend = .021). No associations were found in postmenopausal women. A 14% reduction in BC risk was observed when comparing the highest with the lowest dietary folate tertiles in women having a high (>12 alcoholic drinks/week) alcohol intake (HRT3-T1 = 0.86, 95% CI = 0.75 to 0.98, P interaction = .035). CONCLUSIONS: Higher dietary folate intake may be associated with a lower risk of sex hormone receptor-negative BC in premenopausal women.

Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

BACKGROUND: There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases. RESULTS: During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n=430) and non-aggressive (n=413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend=0.009) and lignans (HRQ5-Q1 0.78, 95% CI: 0.62-0.96; P-trend=0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC. CONCLUSIONS: Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC.

Dietary vitamin D intake and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition: the EPIC-InterAct study.

BACKGROUND/OBJECTIVES: Prospective cohort studies have indicated that serum vitamin D levels are inversely related to risk of type 2 diabetes. However, such studies cannot determine the source of vitamin D. Therefore, we examined the association of dietary vitamin D intake with incident type 2 diabetes within the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study in a heterogeneous European population including eight countries with large geographical variation. SUBJECTS/METHODS: Using a case-cohort design, 11,245 incident cases of type 2 diabetes and a representative subcohort (N=15,798) were included in the analyses. Hazard ratios (HR) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using a Prentice-weighted Cox regression adjusted for potential confounders. Twenty-four-hour diet-recall data from a subsample (N=2347) were used to calibrate habitual intake data derived from dietary questionnaires. RESULTS: Median follow-up time was 10.8 years. Dietary vitamin D intake was not significantly associated with the risk of type 2 diabetes. HR and 95% CIs for the highest compared to the lowest quintile of uncalibrated vitamin D intake was 1.09 (0.97-1.22) (Ptrend=0.17). No associations were observed in a sex-specific analysis. The overall pooled effect (HR (95% CI)) using the continuous calibrated variable was 1.00 (0.97-1.03) per increase of 1 µg/day dietary vitamin D. CONCLUSIONS: This observational study does not support an association between higher dietary vitamin D intake and type 2 diabetes incidence. This result has to be interpreted in light of the limited contribution of dietary vitamin D on the overall vitamin D status of a person.

Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study.

There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow-up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non-significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non-aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers.