Prospective association between late evening food consumption and risk of prediabetes and diabetes: the Whitehall II cohort study.

AIMS: We examined whether late evening food consumption was prospectively associated with the risk of developing prediabetes or diabetes in a large observational study of individuals with normoglycaemia. METHODS: Participants were 2642 men and women with normoglycaemia (HbA1c < 39 mmol/mol; < 5.7%) from the Whitehall II study. Time of last eating episode (TLEE) before the examination day was assessed at baseline. We studied the associations of TLEE with 5-year changes in HbA1c and risk of developing prediabetes or diabetes (HbA1c ≥ 39 mmol/mol; ≥ 5.7%). Potential heterogeneity in the association between TLEE and prediabetes or diabetes was examined using recursive partitioning modelling for time-to-event outcomes. RESULTS: There was a tendency of an overall association of TLEE with change in HbA1c but with little effect size [ß per 1-h increase in TLEE = 0.2 mmol/mol, 95% CI -0.0 to 0.3 (0.01%, -0.00 to 0.03); P = 0.055] and no association with the risk of developing prediabetes/diabetes (risk ratio per 1-h increase in TLEE = 1.03, 95% CI 0.94 to 1.13; P = 0.511). According to the recursive partitioning modelling, women with HbA1c ≤ 36 mmol/mol and TLEE after 21:00 had a 1.51 times (95% CI 1.16 to 1.93) higher 5-year risk of developing prediabetes or diabetes than those having their TLEE between 16:00 and 21:00 (35.4% vs. 23.5%; P = 0.003). CONCLUSIONS: There was no overall association of TLEE with the development of prediabetes or diabetes in the Whitehall II population. However, explorative analyses suggested that eating late in the evening was associated with increased risk of developing prediabetes/diabetes among women with good glycaemic control. Whether restricting late evening food consumption is effective and feasible for the prevention of Type 2 diabetes needs testing in randomized controlled trials.

Earlier depression and later-life self-reported chewing difficulties: results from the Whitehall II study.

This study aimed to assess, whether depression in adulthood was associated with self-reported chewing difficulties at older age, and examine whether the strength of the association differed according to the number of depression episodes in earlier adult life. We used Whitehall II study data from 277 participants who completed a questionnaire in 2011. Depression was measured with the Center for Epidemiologic Studies Depression Scale (CES-D) in 2003 and 2008. The association between CES-D depression and self-reported chewing ability was assessed using regression models adjusted for some socio-demographic factors. Participants with depression at some point in their earlier adulthood had an odds ratio (95% CI) of 2·01 (1·06, 3·82) for reporting chewing difficulties in older adulthood, compared to those without depression. The respective odds ratios were 1·42 (0·66, 3·04) for individuals with depression in only one phase, but 3·53 (1·51, 8·24) for those with depression in two phases. In conclusion, while further research is required, there was an association between depression and chewing difficulty that was independent of demographic and socio-economic characteristics. Furthermore, this increased odds for chewing difficulties was primarily among adults that experienced two episodes or a prolonged period of depression.

Effect of time of day and fasting duration on measures of glycaemia: analysis from the Whitehall II Study.

AIMS/HYPOTHESIS: We aimed to study diurnal variation in glucose regulation by examining the effects of time of day and fasting duration on fasting plasma glucose (FPG), 2 h post-load plasma glucose (2hPG) and HbA(1c) levels. METHODS: We analysed data from 5,978 non-diabetic white men and women from the prospective Whitehall II Study. All studied participants fasted for at least 8 h before a clinical examination, which included an OGTT and anthropometric measurements. We fitted mixed-effects models for FPG, 2hPG and HbA(1c) as outcome variables, and time of day and/or fasting duration as explanatory variables. Models were adjusted for age, BMI and study phase. RESULTS: Time of day and fasting duration were associated inversely with FPG and positively with 2hPG. The mean difference between measures at 08:00 and 15:00 hours in men/women was -0.46 (95% CI -0.50, -0.42) mmol/l/-0.39 (95% CI -0.46, -0.31) mmol/l and 1.39 (95% CI 1.25, 1.52) mmol/l/1.19 (95% CI 0.96, 1.42) mmol/l for FPG and 2hPG, respectively. HbA(1c) levels were independent of either time. Time of day and fasting duration were independently associated with 2hPG. In contrast, the effect of fasting duration on FPG was markedly attenuated with adjustment for time of day. Ageing, but not obesity, was associated with increased diurnal variation in glucose tolerance. CONCLUSIONS/INTERPRETATION: Both time of day and fasting duration should be considered in clinical practice and epidemiological studies, since they have clinically relevant effects on FPG and 2hPG levels. As biochemically expected, HbA(1c) levels are independent of time of blood sampling and fasting duration.

Incidence and prognosis of angina pectoris in South Asians and Whites: 18 years of follow-up over seven phases in the Whitehall-II prospective cohort study.

BACKGROUND: Whether the higher coronary mortality in South Asians compared with White populations is due to a higher incidence of disease is not known. This study assessed cumulative incidence of chest pain in South Asians and Whites, and prognosis of chest pain. METHODS: Over seven phases of 18-year follow-up of the Whitehall-II study (9,775 civil servants: 9,195 White, 580 South Asian), chest pain was assessed using the Rose questionnaire. Coronary death/non-fatal myocardial infarction was examined comparing those with chest pain to those with no chest pain at baseline. RESULTS: South Asians had higher cumulative frequencies of typical angina by Phase 7 (17.0 versus 11.3%, P < 0.001) and exertional chest pain (15.4 versus 8.5%, P < 0.001) compared with Whites. Typical angina and exertional chest pain at baseline were associated with a worse prognosis compared with those with no chest pain in both groups (typical angina, South Asians: HR, 4.67 and 95% CI, 2.12-0.30; Whites: HR, 3.56 95% CI, 2.59-4.88). Baseline non-exertional chest pain did not confer a worse prognosis. Across all types of pain, prognosis was worse in South Asians. CONCLUSION: South Asians had higher cumulative incidence of angina than Whites. In both, typical angina and exertional chest pain were associated with worse prognosis compared with those with no chest pain.

Alcohol intake and risk of colorectal cancer: results from the UK Dietary Cohort Consortium.

BACKGROUND: Epidemiological studies have suggested that excessive alcohol intake increases colorectal cancer (CRC) risk. However, findings regarding tumour subsites and sex differences have been inconsistent. METHODS: We investigated the prospective associations between alcohol intake on overall and site- and sex-specific CRC risk. Analyses were conducted on 579 CRC cases and 1996 matched controls nested within the UK Dietary Cohort Consortium using standardised data obtained from food diaries as a main nutritional method and repeated using data from food frequency questionnaire (FFQ). RESULTS: Compared with individuals in the lightest category of drinkers (>0-<5 g per day), the multivariable odds ratios of CRC were 1.16 (95% confidence interval (95% CI): 0.88, 1.53) for non-drinkers, 0.91 (95% CI: 0.67, 1.24) for drinkers with 5-<15 g per day, 0.90 (95% CI: 0.65, 1.25) for drinkers with 15-<30 g per day, 1.02 (95% CI: 0.66, 1.58) for drinkers with 30-<45 g per day and 1.19 (95% CI: 0.75, 1.91) for drinkers with >or=45 g per day. No clear associations were observed between site-specific CRC risk and alcohol intake in either sex. Analyses using FFQ showed similar results. CONCLUSION: We found no significantly increased risk of CRC up to 30 g per day of alcohol intake within the UK Dietary Cohort Consortium.

Performance of existing risk scores in screening for undiagnosed diabetes: an external validation study.

AIM: To compare the performance of nine published strategies for the selection of individuals prior to screening for undiagnosed diabetes. METHODS: We conducted a validation study, based on a cross-sectional analysis of 6990 participants of the Whitehall II study, an occupational cohort of civil servants in London. We calculated sensitivity, specificity and the area under the receiver operating characteristic (ROC) curve, indicative of the ability of a risk score to correctly identify those with undiagnosed diabetes. RESULTS: The prevalence of unknown diabetes was 2.0%. At a set level of sensitivity (0.70), the specificity of the different scores ranged between 0.41 and 0.57. A reference model, based solely on age and body mass index had an area under the ROC curve of 0.67 [95% confidence interval (CI): 0.62, 0.72]. Four scores had a lower area under the ROC curve (lowest ROC AUC: 0.62; 95% CI: 0.58, 0.67) compared with the reference model, while the other five scores had similar areas (highest ROC AUC: 0.68; 95% CI: 0.63, 0.72). All ROC curve areas were lower than those reported in the original publications and validation studies. CONCLUSIONS: Existing risk scores for the detection of undiagnosed diabetes perform less well in a large validation cohort compared with previous validation studies. Our study indicates that non-invasive risk scores require further refinement and testing before they can be used as the first step in a diabetes screening programme.

Do the Joint British Society (JBS2) guidelines on prevention of cardiovascular disease with respect to plasma glucose improve risk stratification in the general population? Prospective cohort study.

AIMS: British guidelines on vascular disease prevention recommend adding a random (casual) blood glucose measurement to a lipid profile in those aged > or = 40 years. To assess this recommendation, we compared the predictive value of a risk model based on the Framingham risk score alone to one which additionally included information on fasting blood glucose, with respect to incident coronary heart disease (CHD) over 11 years. METHOD: Men and women aged 40-63 years in Whitehall II were followed up for incident CHD: death/non-fatal myocardial infarction; angina confirmed by doctor diagnosis or electrocardiogram (ECG) and all first events. Fasting blood glucose was specified as a continuous variable or categorized by World Health Organization (WHO) 1999 glycaemic status (normal glucose tolerance, impaired fasting glucose or newly diagnosed diabetes). RESULTS: The hazard ratio for incident CHD was 1.10 (95%CI 1.09; 1.12) in men and 1.13 (1.10; 1.17) in women per percentage point increase in Framingham risk. The excess risk remained unchanged in models which added glycaemic status or continuous fasting glucose. The area under the receiver operating characteristic (ROC) curve for the Framingham score and incident coronary heart disease [0.70 (0.68; 0.73)] did not change when glycaemic status or fasting glucose was added to the prediction model. Reclassification with these modified models improved discrimination based on the Framingham score alone when glycaemic status was added, net reclassification improvement 2.4% (95% CI 0.2%; 4.6%), but not when fasting glucose was added. CONCLUSION: Better detection of unrecognized diabetes is a valuable consequence of including a random blood glucose in a vascular risk profile. Our results suggest that this strategy is unlikely to improve risk stratification for CHD.

Low serum adiponectin predicts 10-year risk of type 2 diabetes and HbA1c independently of obesity, lipids, and inflammation: Whitehall II study.

Our aim of the present work was to study the effect of serum adiponectin on incident diabetes and HbA1c values. We measured baseline serum adiponectin levels in a nested case-control selection (n=140) of the Whitehall II Cohort. Participants (mean [SD] age 50.9 [6.3] years) had no prevalent diabetes or CHD at baseline. Cases (n=55) had incident diabetes according to an oral glucose tolerance test during follow-up (mean: 11.5+/-3.0 years). Adiponectin levels were lower among cases (9.3 microg/ml, 3.2 [median; IQR] vs. 10.5; 3.6, p=0.01). The risk of incident diabetes decreased by 11% (p=0.03) for 1 microg/ml higher adiponectin levels. Higher adiponectin levels were associated with lower HbA1c at follow-up (p<0.05). Both associations were stable to adjustment for age, sex, body mass index, systolic blood pressure, and serum lipids, and for the case of HbA1c, also for C-reactive protein (all p<0.05). The observed robust, prospective associations support that adiponectin is an independent predictor of diabetes and the degree of glycaemic impairment.

Cumulative exposure to high-strain and active jobs as predictors of cognitive function: the Whitehall II study.

OBJECTIVES: A high-strain job (a combination of high job demands and low job control) is expected to increase the risk of health problems, whereas an active job (high demands and high control) can be hypothesised to be associated with a greater capacity to learn. We tested associations between high-strain and active jobs and cognitive function in middle-aged men and women. METHODS: Data on 4146 British civil servants (2989 men and 1157 women) aged 35-55 years at baseline came from the Whitehall II study. Cumulative exposure to both high-strain and active jobs was assessed at phases 1 (1985-1988), 2 (1989-1990) and 3 (1991-1993). Cognitive performance was assessed at phases 5 (1997-1999) and 7 (2003-2004) using the following tests: verbal memory, inductive reasoning (Alice Heim), verbal meaning (Mill Hill), phonemic and semantic fluency. Analyses were adjusted for age, sex and employment grade. RESULTS: Longer exposure to high job strain and shorter exposure to active jobs were associated with lower scores in most of the cognitive performance tests. However, these associations disappeared on adjustment for employment grade. Phonemic fluency was an exception to this pattern. Associations between exposure to an active job and phonemic fluency at both follow-up phases were robust to adjustment for employment grade. However, there was no association between exposure to active jobs and change in phonemic fluency score between the follow-up phases after adjustment for employment grade. CONCLUSIONS: In these data, associations between cumulative exposure to high-strain or active jobs and cognition are largely explained by socioeconomic position.

Metabolic syndrome: psychosocial, neuroendocrine, and classical risk factors in type 2 diabetes.

This article summarizes some aspects of stress in the metabolic syndrome at the psychosocial, tissue, and cellular levels. The metabolic syndrome is a valuable research concept for studying population health and social-biological translation. The cluster of cardiovascular risk factors labeled the metabolic syndrome is linked with low socioeconomic status. Systematic differences in diet and physical activity contribute to social patterning of the syndrome. In addition, psychosocial factors including chronic work stress are linked with its development. Psychosocial factors could lead to metabolic perturbations and increase cardiovascular risk via activation of neuroendocrine responses, for example, in the autonomic nervous system and in several hormonal pathways. High glucocorticoid levels will promote lipid storage in visceral rather than subcutaneous adipose tissue. Adipocytes secrete several proinflammatory cytokines, which considered major contributors to increase in oxidants and cell injury. Upregulation of heme oxygenase 1 (HO-1) and peroxidase in the early development of diabetes produces a decrease in oxidative-mediated injury. Increased HO activity is associated with a significant decrease in superoxide, endothelial cell shedding and blood pressure. Finally, it is proposed that overexpression of glutathione peroxidase in beta cells may protect beta cell deterioration from oxidative stress during development of diabetes and hyperglycemia and this may result in attenuation of beta cell failure. If this proves to be the case, then the scene will be set to develop glutathione peroxidase mimetics for use in preclinical and clinical trials.

Dietary advice for reducing cardiovascular risk.

BACKGROUND: Changes in population diet are likely to reduce cardiovascular disease and cancer, but the effect of dietary advice is uncertain. OBJECTIVES: To assess the effects of providing dietary advice to achieve sustained dietary changes or improved cardiovascular risk profile among healthy adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, DARE and HTA databases on The Cochrane Library (Issue 4 2006), MEDLINE (1966 to December 2000, 2004 to November 2006) and EMBASE (1985 to December 2000, 2005 to November 2006). Additional searches were done on CAB Health (1972 to December 1999), CVRCT registry (2000), CCT (2000) and SIGLE (1980 to 2000). Dissertation abstracts and reference lists of articles were checked and researchers were contacted. SELECTION CRITERIA: Randomised studies with no more than 20% loss to follow-up, lasting at least 3 months involving healthy adults comparing dietary advice with no advice or minimal advice. Trials involving children, trials to reduce weight or those involving supplementation were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: Thirty-eight trials with 46 intervention arms (comparisons) comparing dietary advice with no advice were included in the review. 17,871 participants/clusters were randomised. Twenty-six of the 38 included trials were conducted in the USA. Dietary advice reduced total serum cholesterol by 0.16 mmol/L (95% CI 0.06 to 0.25) and LDL cholesterol by 0.18 mmol/L (95% CI 0.1 to 0.27) after 3-24 months. Mean HDL cholesterol levels and triglyceride levels were unchanged. Dietary advice reduced blood pressure by 2.07 mmHg systolic (95% CI 0.95 to 3.19) and 1.15 mmHg diastolic (95% CI 0.48 to 1.85) and 24-hour urinary sodium excretion by 44.2 mmol (95% CI 33.6 to 54.7) after 3-36 months. Three trials reported plasma antioxidants where small increases were seen in lutein and beta-cryptoxanthin, but there was heterogeneity in the trial effects. Self-reported dietary intake may be subject to reporting bias, and there was significant heterogeneity in all the following analyses. Compared to no advice, dietary advice increased fruit and vegetable intake by 1.25 servings/day (95% CI 0.7 to 1.81). Dietary fibre intake increased with advice by 5.99 g/day (95% CI 1.12 to 10.86), while total dietary fat as a percentage of total energy intake fell by 4.49 % (95% CI 2.31 to 6.66) with dietary advice and saturated fat intake fell by 2.36 % (95% CI 1.32 to 3.39). AUTHORS' CONCLUSIONS: Dietary advice appears to be effective in bringing about modest beneficial changes in diet and cardiovascular risk factors over approximately 10 months but longer term effects are not known.

Prostate cancer risk related to foods, food groups, macronutrients and micronutrients derived from the UK Dietary Cohort Consortium food diaries.

BACKGROUND/OBJECTIVES: The influence of dietary factors remains controversial for screen-detected prostate cancer and inconclusive for clinically detected disease. We aimed to examine these associations using prospectively collected food diaries. SUBJECTS/METHODS: A total of 1,717 prostate cancer cases in middle-aged and older UK men were pooled from four prospective cohorts with clinically detected disease (n=663), with routine data follow-up (means 6.6-13.3 years) and a case-control study with screen-detected disease (n=1054), nested in a randomised trial of prostate cancer treatments (ISCTRN 20141297). Multiple-day food diaries (records) completed by men prior to diagnosis were used to estimate intakes of 37 selected nutrients, food groups and items, including carbohydrate, fat, protein, dairy products, fish, meat, fruit and vegetables, energy, fibre, alcohol, lycopene and selenium. Cases were matched on age and diary date to at least one control within study (n=3528). Prostate cancer risk was calculated, using conditional logistic regression (adjusted for baseline covariates) and expressed as odds ratios in each quintile of intake (±95% confidence intervals). Prostate cancer risk was also investigated by localised or advanced stage and by cancer detection method. RESULTS: There were no strong associations between prostate cancer risk and 37 dietary factors. CONCLUSIONS: Prostate cancer risk, including by disease stage, was not strongly associated with dietary factors measured by food diaries in middle-aged and older UK men.

Adrenocortical, autonomic, and inflammatory causes of the metabolic syndrome: nested case-control study.

BACKGROUND: The causes of metabolic syndrome (MS), which may be a precursor of coronary disease, are uncertain. We hypothesize that disturbances in neuroendocrine and cardiac autonomic activity (CAA) contribute to development of MS. We examine reversibility and the power of psychosocial and behavioral factors to explain the neuroendocrine adaptations that accompany MS. METHODS AND RESULTS: This was a double-blind case-control study of working men aged 45 to 63 years drawn from the Whitehall II cohort. MS cases (n=30) were compared with healthy controls (n=153). Cortisol secretion, sensitivity, and 24-hour cortisol metabolite and catecholamine output were measured over 2 days. CAA was obtained from power spectral analysis of heart rate variability (HRV) recordings. Twenty-four-hour cortisol metabolite and normetanephrine (3-methoxynorepinephrine) outputs were higher among cases than controls (+ 0.49, +0.45 SD, respectively). HRV and total power were lower among cases (both -0.72 SD). Serum interleukin-6, plasma C-reactive protein, and viscosity were higher among cases (+0.89, +0.51, and +0.72 SD). Lower HRV was associated with higher normetanephrine output (r=-0.19; P=0.03). Among former cases (MS 5 years previously, n=23), cortisol output, heart rate, and interleukin-6 were at the level of controls. Psychosocial factors accounted for 37% of the link between MS and normetanephrine output, and 7% to 19% for CAA. Health-related behaviors accounted for 5% to 18% of neuroendocrine differences. CONCLUSIONS: Neuroendocrine stress axes are activated in MS. There is relative cardiac sympathetic predominance. The neuroendocrine changes may be reversible. This case-control study provides the first evidence that chronic stress may be a cause of MS. Confirmatory prospective studies are required.

Dietary advice for reducing cardiovascular risk.

BACKGROUND: Changes in population diet are likely to reduce cardiovascular disease and cancer, but the effect of dietary advice is uncertain. OBJECTIVES: To assess the effects of providing dietary advice to achieve sustained dietary changes or improved cardiovascular risk profile among healthy adults. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register on The Cochrane Library (Issue 2 2000), MEDLINE (January 1966 to December 2000), EMBASE (January 1985 to December 2000), DARE (December 2000), CAB Health (December 1999), dissertation abstracts, and reference lists of articles. We contacted researchers in the field. SELECTION CRITERIA: Randomised studies with no more than 20% loss to follow-up, lasting at least three months involving healthy adults comparing dietary advice with no advice or less intensive advice. Trials involving children, trials to reduce weight or those involving supplementation were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: Twenty-three trials with 29 intervention arms (comparisons) comparing dietary advice with no advice were included in the review. Dietary advice reduced total serum cholesterol by 0.13 mmol/l (95% CI 0.03 to 0.23) and LDL cholesterol by 0.13 mmol/l (95% CI 0.01 to 0.25) after 3-12 months. Mean HDL cholesterol levels were unchanged. Dietary advice reduced blood pressure by 2.10 mmHg systolic (95% CI 1.37 to 2.83) and 1.63 mmHg diastolic (95% CI 0.56 to 2.71) and 24-hour urinary sodium excretion by 44.2 mmol (95% CI 33.6 to 54.7) after 3-36 months. Plasma triglycerides, ss-carotene and red cell folate were each measured in one small study which suggested no significant effect. Self-reported dietary intake may be subject to reporting bias, and there was significant heterogeneity in all the following analyses. Compared to no advice, dietary advice increased fruit and vegetable intake by 1.24 servings/day (95% CI 0.43 to 2.05). Dietary fibre intake increased with advice by 7.22 g/day (95% CI 2.84 to 11.60), while total dietary fat as a percentage of total energy intake fell by 6.18 % (95% CI 4.00 to 8.36) with dietary advice and saturated fat intake fell by 3.28 % (95% CI 1.92 to 4.64). AUTHORS' CONCLUSIONS: Dietary advice appears to be effective in bringing about modest beneficial changes in diet and cardiovascular risk factors over approximately 9 months but longer term effects are not known.

Differences in biological risk factors for cardiovascular disease between three ethnic groups in the Whitehall II study.

This study compares risk factors for cardiovascular disease in civil servants of three ethnic groups screened as part of the Whitehall II cohort study. Previously identified risk factors for cardiovascular disease in 360 Afro-Caribbean and 577 South Asian subjects are compared with the 8973 white Caucasian subjects. Controlling for socio-economic status is more precise than in most previous studies of cardiovascular differences between ethnic groups. After controlling for socio-economic confounding factors, age and sex, South Asian subjects were found to have increased prevalence of hypertension (defined as either having systolic pressure of > 160, diastolic pressure of > 95 or being on antihypertensives) OR 2.3 (95% CI 1.6-3.3), diabetes OR 4.2 (95%, CI 3.0-5.8) and a high risk lipid profile, although total cholesterol was lower than in the white population. Afro-Caribbean subjects had more hypertension OR 4.0 (95% CI 2.8-5.7) and diabetes OR 2.8 (95% CI 1.7-4.6), but this was accompanied by a favourable lipid profile with low cholesterol and high HDL. Afro-Caribbean alcohol and smoking habits were low-risk. Socio-economic status was found to be an important confounding factor for ethnic differences in biochemical risk factors for cardiovascular disease. However, adjusting for socioeconomic class only attenuates observed differences; it does not abolish them.

Gender and employment grade differences in blood cholesterol, apolipoproteins and haemostatic factors in the Whitehall II study.

In the first Whitehall study, plasma cholesterol was a strong predictor of coronary heart disease (CHD) but it showed a positive association with grade of employment: the higher the grade the higher the level. Because it could not explain the higher rate of CHD in lower employment grades, further investigation of biochemical CHD risk factors has been conducted with data from the baseline examination of the Whitehall II cohort in 1985-88. These data also allow investigation of gender differences and the effect of menopause. Serum cholesterol (6860 men and 3374 women) and apolipoproteins A-I and B (apo AI and apo B) were measured in those aged 35-55 working in the London offices of twenty Civil Service departments. Plasma fibrinogen and factor VII were determined in 45-55 year olds. The apo B/apo AI ratio (95% confidence interval) after age adjustment is lowest in premenopausal women: 0.557 (0.549-0.565), intermediate in postmenopausal women: 0.601 (0.589-0.613) and highest in men: 0.703 (0.698-0.709). After age adjustment fibrinogen is higher in postmenopausal (2.90 (2.85-2.95) g/l) than in premenopausal women (2.78 (2.71-2.84) g/l), who have higher levels than men (2.64 (2.62-2.67) g/l). A positive association with employment grade is seen for apo AI and a negative association is seen for fibrinogen, apo B (women only) and the apo B/apo AI ratio, after age adjustment. These patterns are consistent with the higher rates of CHD in lower grades. Cholesterol and factor VII show no gradient with our sensitive measure of social position. After adjusting for the effects of smoking rates, alcohol consumption, exercise and dietary pattern, as well as age, ethnicity, body mass index and report of symptoms, the regression coefficient for apo AI on employment grade is reduced by 43% in men and 70% in women. Corresponding reductions for fibrinogen are 53% and 65%. These attenuations suggest that a considerable part of the social gradients in apo AI and fibrinogen are explained by variations in health related behaviours. The remaining gradients may represent effects independent of these behaviours.

A comparison of overnight and 24 hour collection to measure urinary catecholamines.

The period of urine collection used to measure excretion of catecholamines varies in epidemiological practice. We set out to compare overnight with 24 hour collection. Twenty-four subjects each collected urine for 24 hours, with the overnight urine being separately collected. The correlation of overnight and 24 hour catecholamines was highest when both measures were standardised for creatinine excretion and when creatinine excretion was adjusted for urine flow rate. The observed correlations were 0.74 for dopamine, 0.81 for noradrenaline and 0.54 for adrenaline. The use of overnight collections may therefore require a sample size up to 1.5 times as large (for noradrenaline) or 3.4 times as large (for adrenaline) to achieve the same power as with 24 hour collections. However, the figures given exaggerate the advantage of 24 hour collections if these incorporate measurement errors that are not present in overnight collections.

Dietary assessment in Whitehall II: the influence of reporting bias on apparent socioeconomic variation in nutrient intakes.

OBJECTIVE: To assess socio-economic differences in nutrient intake, giving particular consideration to the influence of reporting bias. DESIGN: Cross-sectional study. Three methods of data analysis (inclusion of all subjects, exclusion of low energy reporters, and regression-based energy adjustment) were evaluated against biomarkers of fatty acid and antioxidant intakes. SETTING: London-based Civil Servants. SUBJECTS: Age and employment grade stratified random sub-sample of 459 men and 406 women aged 39-61 y who completed 7 d diet diaries at Phase 3 follow-up (1991-93) of the Whitehall II Study. DIETARY MEASURES: Mean daily intakes by employment grade (6 levels) of dietary energy, total fat, saturated fatty acids, polyunsaturated fatty acids (PUFA), linoleic acid, carbohydrate excluding fibre, dietary fibre, protein, alcohol, vitamin C, vitamin E, carotenes, potassium and calcium. Biomarkers: serum cholesterol ester fatty acids (CEFA), total cholesterol, plasma alpha-tocopherol and beta-carotene. RESULTS: Low energy reporting (LER), defined as a reported energy intake below 1.2 times calculated basal metabolic rate, was strongly associated with employment grade (top grade: men 17.3%, women 19.3%, bottom grade: men 45.7%, women 49.2% trend P < 0.0001 both sexes). This association is only to a small extent accounted for by the relative weight distribution across grades. The direct associations with grade--high status, high intakes--of total fat, saturated and polyunsaturated fatty acids seen in the results overall were greatly reduced or abolished when LER were excluded or when energy adjustment was used. Direct associations between grade and intakes of vitamin C and potassium in both sexes were evident regardless of data presentation method. Spearman correlations between biomarkers and reported intakes, for example CEFA and dietary linoleate (men 0.46, women 0.61), plasma beta-carotene/cholesterol ratio and dietary carotenes (men 0.16, women 0.21) together with theoretical considerations indicate that energy adjustment may be the preferred method for reducing the influence of reporting bias. CONCLUSIONS: Low energy reporting is a major source of bias in dietary surveys and its prevalence shows a marked inverse association with socio-economic status. The energy adjustment method provides an approach which reduces this bias without exclusion of low energy reporters. Intakes of micronutrients including vitamin C, rather than fatty acids, showed associations with socio-economic status consistent with a dietary explanation for social inequalities in cardiovascular disease.

Dietary patterns derived with multiple methods from food diaries and breast cancer risk in the UK Dietary Cohort Consortium.

BACKGROUND/OBJECTIVES: In spite of several studies relating dietary patterns to breast cancer risk, evidence so far remains inconsistent. This study aimed to investigate associations of dietary patterns derived with three different methods with breast cancer risk. SUBJECTS/METHODS: The Mediterranean Diet Score (MDS), principal components analyses (PCA) and reduced rank regression (RRR) were used to derive dietary patterns in a case-control study of 610 breast cancer cases and 1891 matched controls within four UK cohort studies. Dietary intakes were collected prospectively using 4- to 7-day food diaries and resulting food consumption data were grouped into 42 food groups. Conditional logistic regression models were used to estimate odds ratios (ORs) for associations between pattern scores and breast cancer risk adjusting for relevant covariates. A separate model was fitted for post-menopausal women only. RESULTS: The MDS was not associated with breast cancer risk (OR comparing first tertile with third 1.20 (95% CI 0.92; 1.56)), nor the first PCA-derived dietary pattern, explaining 2.7% of variation of diet and characterized by cheese, crisps and savoury snacks, legumes, nuts and seeds (OR 1.18 (95% CI 0.91; 1.53)). The first RRR-derived pattern, a 'high-alcohol' pattern, was associated with a higher risk of breast cancer (OR 1.27; 95% CI 1.00; 1.62), which was most pronounced in post-menopausal women (OR 1.46 (95% CI 1.08; 1.98)). CONCLUSIONS: A 'high-alcohol' dietary pattern derived with RRR was associated with an increased breast cancer risk; no evidence of associations of other dietary patterns with breast cancer risk was observed in this study.