The risk for cardiovascular disease and total mortality associated with hemoglobin A1c concentrations increased continuously through the sample distribution. Most of the events in the sample occurred in persons with moderately elevated HbA1c concentrations. These findings support the need for randomized trials of interventions to reduce hemoglobin A1c concentrations in persons without diabetes.

BackgroundThere is overwhelming evidence that behavioural factors influence health, but their combined impact on the general population is less well documented. We aimed to quantify the potential combined impact of four health behaviours on mortality in men and women living in the general community.Methods and FindingsWe examined the prospective relationship between lifestyle and mortality in a prospective population study of 20,244 men and women aged 45–79 y with no known cardiovascular disease or cancer at baseline survey in 1993–1997, living in the general community in the United Kingdom, and followed up to 2006. Participants scored one point for each health behaviour: current non-smoking, not physically inactive, moderate alcohol intake (1–14 units a week) and plasma vitamin C >50 mmol/l indicating fruit and vegetable intake of at least five servings a day, for a total score ranging from zero to four. After an average 11 y follow-up, the age-, sex-, body mass–, and social class–adjusted relative risks (95% confidence intervals) for all-cause mortality(1,987 deaths) for men and women who had three, two, one, and zero compared to four health behaviours were respectively, 1.39 (1.21–1.60), 1.95 (1.70–-2.25), 2.52 (2.13–3.00), and 4.04 (2.95–5.54) p < 0.001 trend. The relationships were consistent in subgroups stratified by sex, age, body mass index, and social class, and after excluding deaths within 2 y. The trends were strongest for cardiovascular causes. The mortality risk for those with four compared to zero health behaviours was equivalent to being 14 y younger in chronological age.ConclusionsFour health behaviours combined predict a 4-fold difference in total mortality in men and women, with an estimated impact equivalent to 14 y in chronological age.

Objective To examine the value of glycated haemoglobin (HbA 1c ) concentration, a marker of blood glucose concentration, as a predictor of death from cardiovascular and all causes in men. Design Prospective population study. Setting Norfolk cohort of European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk). Subjects 4662 men aged 45-79 years who had had glycated haemoglobin measured at the baseline survey in 1995-7 who were followed up to December 1999. Main outcome measures Mortality from all causes, cardiovascular disease, ischaemic heart disease, and other causes. Results Men with known diabetes had increased mortality from all causes, cardiovascular disease, and ischaemic disease (relative risks 2.2, 3.3, and 4.2, respectively, P < 0.001 independent of age and other risk factors) compared with men without known diabetes. The increased risk of death among men with diabetes was largely explained by HbA 1c concentration. HbA 1c was continuously related to subsequent all cause, cardiovascular, and ischaemic heart disease mortality through the whole population distribution, with lowest rates in those with HbA 1c concentrations below 5%. An increase of 1% in HbA 1c was associated with a 28% (P < 0.002) increase in risk of death independent of age, blood pressure, serum cholesterol, body mass index, and cigarette smoking habit; this effect remained (relative risk 1.46, P = 0.05 adjusted for age and risk factors) after men with known diabetes, a HbA 1c concentration >7%, or history of myocardial infarction or stroke were excluded. 18% of the population excess mortality risk associated with a HbA 1c concentration >5% occurred in men with diabetes, but 82% occurred in men with concentrations of 5%-6.9% (the majority of the population). Conclusions Glycated haemoglobin concentration seems to explain most of the excess mortality risk of diabetes in men and to be a continuous risk factor through the whole population distribution. Preventive efforts need to consider not just those with established diabetes but whether it is possible to reduce the population distribution of HbA 1c through behavioural means.

Objectives: Despite increasing interest in the concept of calibration in dietary surveys, there is still little experience in the use and standardization of a common reference dietary method, especially in international studies. In this paper, we present the general theoretical framework and the approaches developed to standardize the computer-assisted 24 h diet recall method (EPIC-SOFT) used to collect about 37 000 24-h dietary recall measurements (24-HDR) from the 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). In addition, an analysis of variance was performed to examine the level of standardization of EPIC-SOFT across the 90 interviewers involved in the study. Methods: The analysis of variance used a random effects model in which mean energy intake per interviewer was used as the dependent variable, while age, body mass index (BMI), energy requirement, week day, season, special diet, special day, physical activity and the EPIC-SOFT version were used as independent variables. The analysis was performed separately for men and women. Results: The results show no statistical difference between interviewers in all countries for men and ®ve out of eight countries for women, after adjustment for physical activity and the EPIC-SOFT program version used, and the exclusion of one interviewer in Germany (for men), and one in Denmark (for women). These results showed an interviewer effect in certain countries and a signi®cant difference between gender, suggesting an underlying respondent's effect due to the higher under-reporting among women that was consistently observed in EPIC. However, the actual difference between interviewer and country mean energy intakes is about 10%. Furthermore, no statistical differences in mean energy intakes were observed across centres from the same country, except in Italy and Germany for men, and France and Spain for women, where the populations were recruited from areas scattered throughout the countries. Conclusion: Despite these encouraging results and the efforts to standardize the 24-HDR interview method, conscious or unconscious behaviour of respondents andaor interviewer bias cannot be prevented entirely. Further evaluation of the reliability of EPIC-SOFT measurements will be conducted through validation against independent biological markers (nitrogen, potassium).

Background-Body fat distribution has been cross-sectionally associated with atherosclerotic disease risk factors, but the prospective relation with coronary heart disease remains uncertain. Methods and Results-We examined the prospective relation between fat distribution indices and coronary heart disease among 24 508 men and women 45 to 79 years of age using proportional hazards regression. During a mean 9.1 years of follow-up, 1708 men and 892 women developed coronary heart disease. The risk for developing subsequent coronary heart disease increased continuously across the range of waist-hip ratio. Hazard ratios (95% CI) of the top versus bottom fifth of waist-hip ratio were 1.55 (1.28 to 1.73) in men and 1.91 (1.44 to 2.54) in women after adjustment for body mass index and other coronary heart disease risk factors. Hazard ratios increased with waist circumference, but risk estimates for waist circumference without hip circumference adjustment were lower by 10% to 18%. After adjustment for waist circumference, body mass index, and coronary heart disease risk factors, hazard ratios for 1-SD increase in hip circumference were 0.80 (95% CI, 0.74 to 0.87) in men and 0.80 (95% CI, 0.69 to 0.93) in women. Hazard ratios for body mass index were greatly attenuated when we adjusted for waist-hip ratio or waist circumference and other covariates. Conclusions-Indices of abdominal obesity were more consistently and strongly predictive of coronary heart disease than body mass index. These simple and inexpensive measurements could be used to assess obesity-related coronary heart disease risk in relatively healthy men and women.

Guarantor: N Slimani. Contributors: NS was the overall coordinator of the ENDB project and in charge of the preparation of the paper in collaboration with the other co-authors. GD, JV, GS, SS, MP, IU, DATS, NS were members of the 'task force group' involving specific managerial or technical tasks for the project and/or the preparation of reference ENDB guidelines. IU was also in charge of the development of the DBMS in collaboration with the coordinating centre. SS, MP, PG, AM, JI, WB, AF, SW, EV, JU, SC and AB were involved as the national compilers in charge of documenting, compiling and evaluating the subset of their national nutrient databases used in the ENDB project. AM, JI, WB and IU were also involved as members of the 'ENDB expert group' headed by DATS, in charge of revising the reference ENDB guidelines. MN, MCB-R, CS, AT, SN, IM, JR, HB, MO, PHMP, PJ, PA, DE, EL, MS de M, AT, KG, CS, SR, AW, SB were involved as local EPIC collaborators in the supervision and preparation of EPIC-specific databases relevant to the ENDB project (e.g. recipe files). CC and MvB, at the coordinating centre, were involved in tasks relevant to these EPIC databases. AFS has provided long-standing scientific collaboration and support for setting up the ENDB. ER is the overall coordinator of the EPIC study. All co-authors provided comments and suggestions on the manuscript. Objective: This paper describes the ad hoc methodological concepts and procedures developed to improve the comparability of Nutrient databases (NDBs) across the 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). This was required because there is currently no European reference NDB available. Design: A large network involving national compilers, nutritionists and experts on food chemistry and computer science was set up for the 'EPIC Nutrient DataBase' (ENDB) project. A total of 550-1500 foods derived from about 37 000 standardized EPIC 24-h dietary recalls (24-HDRS) were matched as closely as possible to foods available in the 10 national NDBs. The resulting national data sets (NDS) were then successively documented, standardized and evaluated according to common guidelines and using a DataBase Management System specifically designed for this project. The nutrient values of foods unavailable or not readily available in NDSs were approximated by recipe calculation, weighted averaging or adjustment for weight changes and vitamin/mineral losses, using common algorithms. Results: The final ENDB contains about 550-1500 foods depending on the country and 26 common components. Each component value was documented and standardized for unit, mode of expression, definition and chemical method of analysis, as far as possible. Furthermore, the overall completeness of NDSs was improved (X99%), particularly for b-carotene and vitamin E. Conclusion: The ENDB constitutes a first real attempt to improve the comparability of NDBs across European countries. This methodological work will provide a useful tool for nutri...

Results from analysis of 24 h urine collections, verified for completeness with para-amino benzoic acid, and blood samples collected over 1 year were compared with 16 d weighed records of all food consumed collected over the year, and with results from 24 h recalls, food-frequency questionnaires and estimated food records in 160 women. Using the weighed records, individuals were sorted into quintiles of the distribution of the urine N excreti0n:dietary N intake ratio (UN:DN). UN exceeded DN in the top quintile of this ratio; mean ratio UN:DN = 1.13. Individuals in this top quintile were heavier, had significantly greater body mass indices, were reportedly more restrained eaters, had significantly lower energy intake:basal metabolic rate ratios (EI:BMR), and had correlated ratios of UN:DN and EI : BMR (r -0.62). Those in the top quintile reported lower intakes of energy and energy-yielding nutrients, Ca, fats, cakes, breakfast cereals, milk and sugars than individuals in the other quintiles but not lower intakes of non-starch polysaccharides, vitamin C, vegetables, potatoes or meat. Correlations between dietary intake from weighed records and 24 h urine K were 0.74 and 0.82, and between dietary vitamin C and &carotene and plasma vitamin C and &carotene 0.86 and 0.48. Correlations between dietary N intake from weighed records and 24 h urine excretion were high (0-78-0.87). Those between N from estimated food records and urine N were r 0-60-0.70. Correlations between urine N and 24 h recalls and food-frequency questionnaires were in the order of 0.01 to 0.5. Despite problems of underreporting in overweight individuals in 20% of this sample, weighed records remained the most accurate method of dietary assessment, and only an estimated 7 d diary was able to approach this accuracy. Dietary assessment methods: Urine nitrogen: Dietary nitrogenThe validity of measurements of dietary intake in free-living individuals is difficult to assess because all methods rely on information given by the subjects themselves, which may not be correct. In an attempt to determine objective measures for validating dietary assessments, the search has begun for analytes of biological specimens that closely reflect dietary intake, but which do not rely on reports of food consumption (Isaksson, 1980;Bingham, 1987). In individuals in energy and N balance, urine N as assessed from 8 d of complete 24 h urine available at https://www.cambridge.org/core/terms. https://doi

Objective: To describe methods and dietary habits of a large population cohort. Design: Prospective assessment of diet using diet diaries and food-frequency questionnaires, and biomarkers of diet in 24-h urine collections and blood samples. Setting: Free living individuals aged 45 to 75 years living in Norfolk, UK. Subjects: Food and nutrient intake from a food-frequency questionnaire on 23 003 men and women, and from a 7-day diet diary from 2117 men and women. Nitrogen, sodium and potassium excretion was obtained from single 24-h urine samples from 300 individuals in the EPIC cohort. Plasma vitamin C was measured for 20 846 men and women. Results: The food-frequency questionnaire (FFQ) and the food diary were able to determine differences in foods and nutrients between the sexes and were reliable as judged by repeated administrations of each method. Plasma vitamin C was significantly higher in women than men. There were significant P , 0X001 differences in mean intake of all nutrients measured by the two different methods in women but less so in men. The questionnaire overestimated dairy products and vegetables in both men and women when compared with intakes derived from the diary, but underestimated cereal and meat intake in men. There were some consistent trends with age in food and nutrient intakes assessed by both methods, particularly in men. Correlation coefficients between dietary intake assessed from the diary and excretion of nitrogen and potassium in a single 24-h urine sample ranged from 0.36 to 0.47. Those comparing urine excretion and intake assessed from the FFQ were 0.09 to 0.26. The correlations between plasma vitamin C and dietary intake from the first FFQ, 24-h recall or diary were 0.28, 0.35 and 0.40. Conclusions: EPIC Norfolk is one of the largest epidemiological studies of nutrition in the UK and the largest on which plasma vitamin C has been obtained. Methods for obtaining food and nutrient intake are described in detail. The results shown here for food and nutrient intakes can be compared with results from other population studies utilising different methods of assessing dietary intake. The utility of different methods used in different settings within the main EPIC cohort is described. The FFQ is to be used particularly in pooled analyses of risk from diet in relation to cancer incidence within the larger European EPIC study, where measurement error is more likely to be overcome by large dietary heterogeneity on an international basis. Findings in the UK, where dietary variation between individuals is smaller and hence the need to use a more accurate individual method greater, will be derived from the 7-day diary information on a nested case±control basis. 24-h recalls can be used in the event that diary information should not be forthcoming from some eventual cases. Combinations of results utilising all dietary methods and biomarkers may also be possible.