Predicting admissions and time spent in hospital over a decade in a population-based record linkage study: the EPIC-Norfolk cohort.

OBJECTIVE: To quantify hospital use in a general population over 10 years follow-up and to examine related factors in a general population-based cohort. DESIGN: A prospective population-based study of men and women. SETTING: Norfolk, UK. PARTICIPANTS: 11,228 men and 13,786 women aged 40-79 years in 1993-1997 followed between 1999 and 2009. MAIN OUTCOMES MEASURES: Number of hospital admissions and total bed days for individuals over a 10-year follow-up period identified using record linkage; five categories for admissions (from zero to highest ≥ 7) and hospital bed days (from zero to highest ≥ 20 nights). RESULTS: Over a period of 10 years, 18,179 (72.7%) study participants had at least one admission to hospital, 13.8% with 7 or more admissions and 19.9% with 20 or more nights in hospital. In logistic regression models with outcome ≥ 7 admissions, low education level OR 1.14 (1.05 to 1.24), age OR per 10-year increase 1.75 (1.67 to 1.82), male sex OR 1.32 (1.22 to 1.42), manual social class 1.22 (1.13 to 1.32), current cigarette smoker OR 1.53 (1.37 to 1.71) and body mass index >30 kg/m² OR 1.41 (1.28 to 1.56) all independently predicted the outcome with p<0.0001. Results were similar for those with ≥ 20 hospital bed days. A risk score constructed using male sex, manual social class, no educational qualifications; current smoker and body mass index >30 kg/m², estimated percentages of the cohort in the categories of admission numbers and hospital bed days in stratified age bands with twofold to threefold differences in future hospital use between those with high-risk and low-risk scores. CONCLUSIONS: The future probability of cumulative hospital admissions and bed days appears independently related to a range of simple demographic and behavioural indicators. The strongest of these is increasing age with high body mass index and smoking having similar magnitudes for predicting risk of future hospital usage.

Plasma elaidic acid level as biomarker of industrial trans fatty acids and risk of weight change: report from the EPIC study.

BACKGROUND: Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow-up, age, energy, alcohol, smoking status, physical activity, and region. RESULTS: In women, doubling elaidic acid was associated with a decreased risk of weight loss (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.55-0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5-year follow-up (OR = 1.23, 95% CI = 0.97-1.56, p = 0.082) (p-trend<.0001). In men, a trend was observed for doubling elaidic acid level and risk of weight loss (OR = 0.82, 95% CI = 0.66-1.01, p = 0.062) while no significant association was found with risk of weight gain during the 5-year follow-up (OR = 1.08, 95% CI = 0.88-1.33, p = 0.454). No association was found for saturated and cis-monounsaturated fatty acids. CONCLUSIONS: These data suggest that a high intake of industrial trans fatty acids may decrease the risk of weight loss, particularly in women. Prevention of obesity should consider limiting the consumption of highly processed foods, the main source of industrially-produced trans fatty acids.

Association between Mediterranean and Nordic diet scores and changes in weight and waist circumference: influence of FTO and TCF7L2 loci.

BACKGROUND: Several studies have shown that adherence to the Mediterranean Diet measured by using the Mediterranean diet score (MDS) is associated with lower obesity risk. The newly proposed Nordic Diet could hold similar beneficial effects. Because of the increasing focus on the interaction between diet and genetic predisposition to adiposity, studies should consider both diet and genetics. OBJECTIVE: We investigated whether FTO rs9939609 and TCF7L2 rs7903146 modified the association between the MDS and Nordic diet score (NDS) and changes in weight (Δweight), waist circumference (ΔWC), and waist circumference adjusted for body mass index (BMI) (ΔWCBMI). DESIGN: We conducted a case-cohort study with a median follow-up of 6.8 y that included 11,048 participants from 5 European countries; 5552 of these subjects were cases defined as individuals with the greatest degree of unexplained weight gain during follow-up. A randomly selected subcohort included 6548 participants, including 5496 noncases. Cases and noncases were compared in analyses by using logistic regression. Continuous traits (ie, Δweight, ΔWC, and ΔWCBMI) were analyzed by using linear regression models in the random subcohort. Interactions were tested by including interaction terms in models. RESULTS: A higher MDS was significantly inversely associated with case status (OR: 0.98; 95% CI: 0.96, 1.00), ΔWC (ß = -0.010 cm/y; 95% CI: -0.020, -0.001 cm/y), and ΔWCBMI (ß = -0.008; 95% CI:-0.015, -0.001) per 1-point increment but not Δweight (P = 0.53). The NDS was not significantly associated with any outcome. There was a borderline significant interaction between the MDS and TCF7L2 rs7903146 on weight gain (P = 0.05), which suggested a beneficial effect of the MDS only in subjects who carried 1 or 2 risk alleles. FTO did not modify observed associations. CONCLUSIONS: A high MDS is associated with a lower ΔWC and ΔWCBMI, regardless of FTO and TCF7L2 risk alleles. For Δweight, findings were less clear, but the effect may depend on the TCF7L2 rs7903146 variant. The NDS was not associated with anthropometric changes during follow-up.

Dietary factors impact on the association between CTSS variants and obesity related traits.

BACKGROUND/AIMS: Cathepsin S, a protein coded by the CTSS gene, is implicated in adipose tissue biology--this protein enhances adipose tissue development. Our hypothesis is that common variants in CTSS play a role in body weight regulation and in the development of obesity and that these effects are influenced by dietary factors--increased by high protein, glycemic index and energy diets. METHODS: Four tag SNPs (rs7511673, rs11576175, rs10888390 and rs1136774) were selected to capture all common variation in the CTSS region. Association between these four SNPs and several adiposity measurements (BMI, waist circumference, waist for given BMI and being a weight gainer-experiencing the greatest degree of unexplained annual weight gain during follow-up or not) given, where applicable, both as baseline values and gain during the study period (6-8 years) were tested in 11,091 European individuals (linear or logistic regression models). We also examined the interaction between the CTSS variants and dietary factors--energy density, protein content (in grams or in % of total energy intake) and glycemic index--on these four adiposity phenotypes. RESULTS: We found several associations between CTSS polymorphisms and anthropometric traits including baseline BMI (rs11576175 (SNP N°2), p = 0.02, ß = -0.2446), and waist change over time (rs7511673 (SNP N°1), p = 0.01, ß = -0.0433 and rs10888390 (SNP N°3), p = 0.04, ß = -0.0342). In interaction with the percentage of proteins contained in the diet, rs11576175 (SNP N°2) was also associated with the risk of being a weight gainer (p(interaction) = 0.01, OR = 1.0526)--the risk of being a weight gainer increased with the percentage of proteins contained in the diet. CONCLUSION: CTSS variants seem to be nominally associated to obesity related traits and this association may be modified by dietary protein intake.

Genetic polymorphisms in the hypothalamic pathway in relation to subsequent weight change--the DiOGenes study.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in genes encoding the components involved in the hypothalamic pathway may influence weight gain and dietary factors may modify their effects. AIM: We conducted a case-cohort study to investigate the associations of SNPs in candidate genes with weight change during an average of 6.8 years of follow-up and to examine the potential effect modification by glycemic index (GI) and protein intake. METHODS AND FINDINGS: Participants, aged 20-60 years at baseline, came from five European countries. Cases ('weight gainers') were selected from the total eligible cohort (n = 50,293) as those with the greatest unexplained annual weight gain (n = 5,584). A random subcohort (n = 6,566) was drawn with the intention to obtain an equal number of cases and noncases (n = 5,507). We genotyped 134 SNPs that captured all common genetic variation across the 15 candidate genes; 123 met the quality control criteria. Each SNP was tested for association with the risk of being a 'weight gainer' (logistic regression models) in the case-noncase data and with weight gain (linear regression models) in the random subcohort data. After accounting for multiple testing, none of the SNPs was significantly associated with weight change. Furthermore, we observed no significant effect modification by dietary factors, except for SNP rs7180849 in the neuromedin ß gene (NMB). Carriers of the minor allele had a more pronounced weight gain at a higher GI (P = 2 x 10⁻7). CONCLUSIONS: We found no evidence of association between SNPs in the studied hypothalamic genes with weight change. The interaction between GI and NMB SNP rs7180849 needs further confirmation.

Physical activity and gain in abdominal adiposity and body weight: prospective cohort study in 288,498 men and women.

BACKGROUND: The protective effect of physical activity (PA) on abdominal adiposity is unclear. OBJECTIVE: We examined whether PA independently predicted gains in body weight and abdominal adiposity. DESIGN: In a prospective cohort study [the EPIC (European Prospective Investigation into Cancer and Nutrition)], we followed 84,511 men and 203,987 women for 5.1 y. PA was assessed by a validated questionnaire, and individuals were categorized into 4 groups (inactive, moderately inactive, moderately active, and active). Body weight and waist circumference were measured at baseline and self-reported at follow-up. We used multilevel mixed-effects linear regression models and stratified our analyses by sex with adjustments for age, smoking status, alcohol consumption, educational level, total energy intake, duration of follow-up, baseline body weight, change in body weight, and waist circumference (when applicable). RESULTS: PA significantly predicted a lower waist circumference (in cm) in men (ß = -0.045; 95% CI: -0.057, -0.034) and in women (ß = -0.035; 95% CI: -0.056, -0.015) independent of baseline body weight, baseline waist circumference, and other confounding factors. The magnitude of associations was materially unchanged after adjustment for change in body weight. PA was not significantly associated with annual weight gain (in kg) in men (ß = -0.008; 95% CI: -0.02, 0.003) and women (ß = -0.01; 95% CI: -0.02, 0.0006). The odds of becoming obese were reduced by 7% (P < 0.001) and 10% (P < 0.001) for a one-category difference in baseline PA in men and women, respectively. CONCLUSION: Our results suggest that a higher level of PA reduces abdominal adiposity independent of baseline and changes in body weight and is thus a useful strategy for preventing chronic diseases and premature deaths.

A single nucleotide polymorphism in the 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene ( HMGCR) influences the serum triacylglycerol relationship with dietary fat and fibre in the European Prospective Investigation into Cancer and Nutrition in Norfolk (EPIC-Norfolk) study.

The objective of the present study was to investigate the influence of the single nucleotide polymorphism (rs17238540) at the 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene (HMGCR) on the relationship between serum lipids and dietary fat and fibre (NSP). FFQ and pyrosequencing were used to assess cross-sectional dietary intake and HMGCR genotype in a population study with data for serum lipids available. Genotype frequencies and allele distributions for 23 011 participants were: TT 95.65 %, TG 4.29 % and GG 0.06 %; T 97.8 % and G 2.2 %. In regression analyses, the TG+GG group showed a significant positive relationship between TAG and SFA intake (+0.11 (95 % CI 0.02, 0.20) mmol TAG/l; P = 0.017; per 3 % SFA energy increase) while the TT individuals showed no change in the TAG levels related to SFA intake ( - 0.0007 (95 % CI - 0.02, 0.02) mmol TAG/l; P = 0.99). TG+GG individuals showed an inverse relationship between TAG and fibre intake higher ( - 0.14 (95 % CI - 0.22, - 0.05) mmol TAG/l than the TT group ( - 0.04 (95 % CI - 0.06, - 0.02) mmol TAG/l). In both cases the respective coefficient regressions of TAG were different between the genotype groups (Z = 2.27, P = 0.023 for SFA intake; Z = 2.19, P = 0.029 for fibre intake). Individuals carrying the G allele may show a greater response in lower TAG levels with reduced SFA intake and increased fibre intake compared with those homozygous for the T allele. The effectiveness of different dietary interventions to control serum lipids may vary according to HMGCR genotype.

Dietary fiber and subsequent changes in body weight and waist circumference in European men and women.

BACKGROUND: Dietary fiber may play a role in obesity prevention. Until now, the role that fiber from different sources plays in weight change had rarely been studied. OBJECTIVE: Our aim was to investigate the association of total dietary fiber, cereal fiber, and fruit and vegetable fiber with changes in weight and waist circumference. DESIGN: We conducted a prospective cohort study with 89,432 European participants, aged 20-78 y, who were free of cancer, cardiovascular disease, and diabetes at baseline and who were followed for an average of 6.5 y. Dietary information was collected by using validated country-specific food-frequency questionnaires. Multiple linear regression analysis was performed in each center studied, and estimates were combined by using random-effects meta-analyses. Adjustments were made for follow-up duration, other dietary variables, and baseline anthropometric, demographic, and lifestyle factors. RESULTS: Total fiber was inversely associated with subsequent weight and waist circumference change. For a 10-g/d higher total fiber intake, the pooled estimate was -39 g/y (95% CI: -71, -7 g/y) for weight change and -0.08 cm/y (95% CI: -0.11, -0.05 cm/y) for waist circumference change. A 10-g/d higher fiber intake from cereals was associated with -77 g/y (95% CI: -127, -26 g/y) weight change and -0.10 cm/y (95% CI: -0.18, -0.02 cm/y) waist circumference change. Fruit and vegetable fiber was not associated with weight change but had a similar association with waist circumference change when compared with intake of total dietary fiber and cereal fiber. CONCLUSION: Our finding may support a beneficial role of higher intake of dietary fiber, especially cereal fiber, in prevention of body-weight and waist circumference gain.

A truncation mutation in TBC1D4 in a family with acanthosis nigricans and postprandial hyperinsulinemia.

Tre-2, BUB2, CDC16, 1 domain family member 4 (TBC1D4) (AS160) is a Rab-GTPase activating protein implicated in insulin-stimulated glucose transporter 4 (GLUT4) translocation in adipocytes and myotubes. To determine whether loss-of-function mutations in TBC1D4 might impair GLUT4 translocation and cause insulin resistance in humans, we screened the coding regions of this gene in 156 severely insulin-resistant patients. A female presenting at age 11 years with acanthosis nigricans and extreme postprandial hyperinsulinemia was heterozygous for a premature stop mutation (R363X) in TBC1D4. After demonstrating reduced expression of wild-type TBC1D4 protein and expression of the truncated protein in lymphocytes from the proband, we further characterized the biological effects of the truncated protein in 3T3L1 adipocytes. Prematurely truncated TBC1D4 protein tended to increase basal cell membrane GLUT4 levels (P = 0.053) and significantly reduced insulin-stimulated GLUT4 cell membrane translocation (P < 0.05). When coexpressed with wild-type TBC1D4, the truncated protein dimerized with full-length TBC1D4, suggesting that the heterozygous truncated variant might interfere with its wild-type counterpart in a dominant negative fashion. Two overweight family members with the mutation also manifested normal fasting glucose and insulin levels but disproportionately elevated insulin levels following an oral glucose challenge. This family provides unique genetic evidence of TBC1D4 involvement in human insulin action.

Physical activity and dietary behaviour in a population-based sample of British 10-year old children: the SPEEDY study (Sport, Physical activity and Eating behaviour: environmental Determinants in Young people).

BACKGROUND: The SPEEDY study was set up to quantify levels of physical activity (PA) and dietary habits and the association with potential correlates in 9-10 year old British school children. We present here the analyses of the PA, dietary and anthropometry data. METHODS: In a cross-sectional study of 2064 children (926 boys, 1138 girls) in Norfolk, England, we collected anthropometry data at school using standardised procedures. Body mass index (BMI) was used to define obesity status. PA was assessed with the Actigraph accelerometer over 7 days. A cut-off of > or = 2000 activity counts was used to define minutes of moderate-to-vigorous PA (MVPA). Dietary habits were assessed using the Health Behaviour in School Children food questionnaire. Weight status was defined using published international cut-offs (Cole, 2000). Differences between groups were assessed using independent t-tests for continuous data and chi-squared tests for categorical data. RESULTS: Valid PA data (>500 minutes per day on > or = 3 days) was available for 1888 children. Mean (+/- SD) activity counts per minute among boys and girls were 716.5 +/- 220.2 and 635.6 +/- 210.6, respectively (p < 0.001). Boys spent an average of 84.1 +/- 25.9 minutes in MVPA per day compared to 66.1 +/- 20.8 among girls (p < 0.001), with an average of 69.1% of children accumulating 60 minutes each day. The proportion of children classified as overweight and obese was 15.0% and 4.1% for boys and 19.3% and 6.6% for girls, respectively (p = 0.001). Daily consumption of at least one portion of fruit and of vegetables was 56.8% and 49.9% respectively, with higher daily consumption in girls than boys and in children from higher socioeconomic backgrounds. CONCLUSION: Results indicate that almost 70% of children meet national PA guidelines, indicating that a prevention of decline, rather than increasing physical activity levels, might be an appropriate intervention target. Promotion of daily fruit and vegetable intake in this age group is also warranted, possibly focussing on children from lower socioeconomic backgrounds.

Oxygen uptakes adjusted for body composition in normal-weight and obese adolescents.

OBJECTIVE: To test whether resting oxygen uptake (VO(2)), submaximal VO(2), and maximal VO(2) (VO(2max)) differs between obese adolescents (n = 18; BMI > 30) and a matched normal-weight control group after adjustment for differences in fat-free mass (FFM) and fat mass (FM). RESEARCH METHODS AND PROCEDURES: FFM and FM were assessed by DXA. Resting VO(2), submaximal VO(2), and VO(2max) were measured by indirect calorimetry. RESULTS: There was no difference in resting VO(2) between groups after adjusting for FFM and FM. Submaximal VO(2) did not differ between groups after adjusting for body weight. Percentage VO(2max) and NET VO(2) (VO(2max) - resting VO(2)) were significantly higher in the obese group during submaximal exercise, however not after adjusting for body weight. VO(2max) was not significantly different between groups after adjusting for FFM. DISCUSSION: When body compositions are appropriately controlled for, resting VO(2), submaximal VO(2), and VO(2max) do not differ between obese and normal-weight adolescents. These data suggested that the higher relative VO(2) observed in obese adolescent subjects is due to their higher FM and not to an impaired VO(2max) even though they may be less physically active.