Size matters: Grey matter brain reserve predicts executive functioning in the elderly.

Preserved executive functioning (EF) is crucial for daily functioning in the elderly and it appears to predict dementia development. We sought to clarify the role of atrophy-corrected cortical grey matter (GM) volume as a potential brain reserve (BR) marker for EF in the elderly. In total, 206 pre-surgical subjects (72.50 ±â€¯4.95 years; mean MMSE score 28.50) were investigated. EF was primarily assessed using the Trail Making Test B (TMT B). Global/ lobar GM volumes were acquired with T1 MP-RAGE. Adjusting for key covariates including a brain atrophy index (i.e. brain parenchymal fraction), multiple linear regression analysis was used to study associations of GM volumes and TMT B. All GM volumes - most notably of global GM - were significantly associated with TMT B independently of GM atrophy (ß = -0.201 to -0.275, p = 0.001-0.012). Using atrophy-corrected GM volume as an estimate of maximal GM size in youth may serve as a BR predictor for cognitive decline in future studies investigating BR in the elderly.

Personalized risk prediction of postoperative cognitive impairment - rationale for the EU-funded BioCog project.

Postoperative cognitive impairment is among the most common medical complications associated with surgical interventions - particularly in elderly patients. In our aging society, it is an urgent medical need to determine preoperative individual risk prediction to allow more accurate cost-benefit decisions prior to elective surgeries. So far, risk prediction is mainly based on clinical parameters. However, these parameters only give a rough estimate of the individual risk. At present, there are no molecular or neuroimaging biomarkers available to improve risk prediction and little is known about the etiology and pathophysiology of this clinical condition. In this short review, we summarize the current state of knowledge and briefly present the recently started BioCog project (Biomarker Development for Postoperative Cognitive Impairment in the Elderly), which is funded by the European Union. It is the goal of this research and development (R&D) project, which involves academic and industry partners throughout Europe, to deliver a multivariate algorithm based on clinical assessments as well as molecular and neuroimaging biomarkers to overcome the currently unsatisfying situation.

Hypertension and Risk of Post-Operative Cognitive Dysfunction (POCD): A Systematic Review and Meta-Analysis.

BACKGROUND: Post-operative cognitive dysfunction (POCD) occurs frequently after major surgery. Hypertension is well-established as a risk factor for age-related cognitive impairment, but it is unclear whether or not it also increases the risk of POCD. OBJECTIVE: To evaluate the role of hypertension in POCD risk in a systematic review and meta-analysis. METHOD: PubMed, Ovid SP and the Cochrane Database of Systematic Reviews were searched for longitudinal studies of adults undergoing surgery with reporting of hypertension, blood pressure and/or anti-hypertensive treatment associations with POCD as relative risks or odds ratios. Fixed-effects meta-analyses were performed using Review Manager (version 5.3). RESULTS: Twenty-four studies on 4317 patients (mean age 63 years) were included. None of the studies had set out to assess hypertension as a risk factor for POCD. Hypertension was used as a categorical predictor throughout and only 2 studies adjusted for potential confounders. Across all 24 studies, hypertension was not significantly associated with POCD risk (RR 1.01; 95% CI 0.93, 1.09; p=0.82), though among 8 studies with >75% males, we found hypertension associations with a 27% increased risk of POCD (RR 1.27, 95% CI 1.07, 1.49; p=0.005). CONCLUSION: Our findings do not support the hypothesis that hypertension is a risk factor for POCD. However, since none of the studies included in our analysis were hypothesis-driven and most did not adjust for potential confounders, further systematic investigations are needed to evaluate the role of hypertension in the epidemiology of POCD.

Diabetes is associated with risk of postoperative cognitive dysfunction: A meta-analysis.

BACKGROUND: Postoperative cognitive dysfunction (POCD) occurs frequently after surgery, particularly among older people. Diabetes, chronic hyperglycemia, and a history of hypoglycemia are related to cognitive impairment, but little is known about their roles in POCD. Here, we estimated their associations with risk of POCD on the basis of published epidemiological research. METHODS: The PubMed and Cochrane databases were searched for longitudinal studies of adults undergoing surgery with reporting of associations of diabetes status, glycemic levels, and/or a history of hypoglycemia with risk of POCD as relative risks or odds ratios. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. RESULTS: The search identified 246 publications of which 14 met inclusion criteria, reporting on a total of 2642 patients (mean age 64 y). Follow-up periods spanned 1 day to 5 years. Overall, patients with diabetes had a 1.26-fold higher risk of POCD compared with diabetes-free patients (95% CI, 1.12-1.42). A single study assessed glycemic control in patients with diabetes and identified a higher hemoglobin A1c (HbA1c) level as associated with higher POCD risk (relative risk per percent higher HbA1c, 2.0; 95% CI, 1.4-2.6). We did not find studies on glycemic levels in the nondiabetic range or on hypoglycemia as potential predictors of POCD. CONCLUSION: Patients with diabetes appear to have a higher risk of POCD compared with diabetes-free persons. Among patients with diabetes, POCD risk may further increase with poorer glycemic control as indexed by higher HbA1c. The roles of HbA1c levels among nondiabetic persons in POCD risk warrant further research.

Associations of anthropometric markers with serum metabolites using a targeted metabolomics approach: results of the EPIC-potsdam study.

BACKGROUND/OBJECTIVES: The metabolic consequences of type of body shape need further exploration. Whereas accumulation of body mass in the abdominal area is a well-established metabolic risk factor, accumulation in the gluteofemoral area is controversially debated. We evaluated the associations of anthropometric markers of overall body mass and body shape with 127 serum metabolites within a sub-sample of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. SUBJECTS/METHODS: The cross-sectional analysis was conducted in 2270 participants, randomly drawn from the EPIC-Potsdam cohort. Metabolites were measured by targeted metabolomics. To select metabolites related with both waist circumference (WC) (abdominal subcutaneous and visceral fat) and hip circumference (HC) (gluteofemoral fat, muscles and bone structure) correlations (r) with body mass index (BMI) as aggregating marker of body mass (lean and fat mass) were calculated. Relations with body shape were assessed by median metabolite concentrations across tertiles of WC and HC, mutually adjusted to each other. RESULTS: Correlations revealed 23 metabolites related to BMI (r⩾I0.20 I). Metabolites showing relations with BMI were showing similar relations with HC adjusted WC (WCHC). In contrast, relations with WC adjusted HC (HCWC) were less concordant with relations of BMI and WCHC. In both sexes, metabolites with concordant relations regarding WCHC and HCWC included tyrosine, diacyl-phosphatidylcholine C38:3, C38:4, lyso-phosphatidylcholine C18:1, C18:2 and sphingomyelin C18:1; metabolites with opposite relations included isoleucine, diacyl-phosphatidylcholine C42:0, acyl-alkyl-phosphatidylcholine C34:3, C42:4, C42:5, C44:4 and C44:6. Metabolites specifically related to HCWC included acyl-alkyl-phosphatidylcholine C34:2, C36:2, C38:2 and C40:4, and were solely observed in men. Other metabolites were related to WCHC only. CONCLUSIONS: The study revealed specific metabolic profiles for HCWC as marker of gluteofemoral body mass differing from those for BMI and WCHC as markers of overall body mass and abdominal fat, respectively. Thus, the study suggests that gluteofemoral mass may have less-adverse metabolic implications than abdominal fat.

Prediction of activity-related energy expenditure using accelerometer-derived physical activity under free-living conditions: a systematic review.

BACKGROUND/OBJECTIVES: Activity-related energy expenditure (AEE) might be an important factor in the etiology of chronic diseases. However, measurement of free-living AEE is usually not feasible in large-scale epidemiological studies but instead has traditionally been estimated based on self-reported physical activity. Recently, accelerometry has been proposed for objective assessment of physical activity, but it is unclear to what extent this methods explains the variance in AEE. SUBJECTS/METHODS: We conducted a systematic review searching MEDLINE database (until 2014) on studies that estimated AEE based on accelerometry-assessed physical activity in adults under free-living conditions (using doubly labeled water method). Extracted study characteristics were sample size, accelerometer (type (uniaxial, triaxial), metrics (for example, activity counts, steps, acceleration), recording period, body position, wear time), explained variance of AEE (R(2)) and number of additional predictors. The relation of univariate and multivariate R(2) with study characteristics was analyzed using nonparametric tests. RESULTS: Nineteen articles were identified. Examination of various accelerometers or subpopulations in one article was treated separately, resulting in 28 studies. Sample sizes ranged from 10 to 149. In most studies the accelerometer was triaxial, worn at the trunk, during waking hours and reported activity counts as output metric. Recording periods ranged from 5 to 15 days. The variance of AEE explained by accelerometer-assessed physical activity ranged from 4 to 80% (median crude R(2)=26%). Sample size was inversely related to the explained variance. Inclusion of 1 to 3 other predictors in addition to accelerometer output significantly increased the explained variance to a range of 12.5-86% (median total R(2)=41%). The increase did not depend on the number of added predictors. CONCLUSIONS: We conclude that there is large heterogeneity across studies in the explained variance of AEE when estimated based on accelerometry. Thus, data on predicted AEE based on accelerometry-assessed physical activity need to be interpreted cautiously.

Smoking, Smoking Cessation, and Risk of Tooth Loss: The EPIC-Potsdam Study.

The aim of this study was to investigate the association between cigarette smoking and smoking cessation and the prevalence and incidence of tooth loss in a large cohort study in Germany. We analyzed data of 23,376 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study recruited between 1994 and 1998 from the general population in Potsdam and other parts of Brandenburg, Germany, who had complete data on cigarette smoking, tooth loss, and covariates. Negative binomial regression and tooth-specific logistic regression models were fit to evaluate the association between smoking and the baseline prevalence and incidence of tooth loss during follow-up, respectively. Cigarette smoking was associated with higher prevalence of tooth loss at baseline as well as higher incidence of tooth loss during follow-up. The association between smoking and the incidence of tooth loss was stronger in men than women and stronger in younger versus older individuals. Heavy smoking (≥15 cigarettes/d) was associated with >3 times higher risk of tooth loss in men (odds ratio, 3.6; 95% confidence interval, 3.0, 4.4) and more than twice the risk of tooth loss in women (odds ratio, 2.5; 95% confidence interval, 2.1, 2.9) younger than 50 y when compared with never smokers. Smoking cessation was consistently associated with a reduction in tooth loss risk, with the risk of tooth loss approaching that of never smokers after approximately 10 to 20 y of cessation.

Regional distribution of body fat in relation to DNA methylation within the LPL, ADIPOQ and PPARγ promoters in subcutaneous adipose tissue.

Obesity may be related to differential DNA methylation and thus to differential expression of key genes in adipose tissue metabolism, such as LPL, ADIPOQ and PPARγ. Using subcutaneous adipose tissue (SAT) from 59 individuals of the European Prospective Investigation into Cancer and Nutrition-Potsdam study, we performed quantitative DNA methylation analysis within the promoters of LPL (LPL-CG1 and -CG2), ADIPOQ (ADIPOQ-CG1 and-CG2) and PPARγ (PPARγ-CG1). We then studied DNA methylation in relation to SAT gene expression, body composition measured using whole-body magnetic resonance imaging, body mass index (BMI), waist circumference (WC) and long-term changes in BMI and WC. For LPL-CG1 and LPL-CG2, higher methylation levels were associated with lower LPL expression, but with higher past WC gain. LPL-CG1 was also positively associated with BMI, WC, and visceral and subcutaneous fat mass. ADIPOQ-CG1 or -CG2 methylation exhibited no association with ADIPOQ expression or with anthropometric parameters. PPARγ-CG1 methylation was significantly higher in individuals with higher visceral fat mass. Among the investigated sites, LPL-CG1 methylation showed the strongest association with gene expression and regional body fat distribution, thereby possibly linking the degree of obesity with major metabolic processes in SAT.

Body weight gain and risk of colorectal cancer: a systematic review and meta-analysis of observational studies.

While the relationship between body mass index as an indicator of excess body weight and the risk of colorectal cancer (CRC) is well established, the association between body weight gain in adulthood and risk of CRC remains unresolved. We quantified this association in a meta-analysis of 12 observational studies published until November 2014 with a total of 16,151 incident CRC cases. Random effect models were used to obtain summary relative risks (RR) and 95% confidence intervals (95% CIs). Between-study heterogeneity was assessed using I(2) statistics. Overall, the summary RR (95% CI) was 1.22 (1.14-1.30) for high body weight gain (midpoint: 15.2 kg) compared with stable weight (P for heterogeneity = 0.182; I(2) = 21.2%). In a dose-response analysis, each 5 kg weight gain was associated with a 4% (95% CI: 2%-5%) higher risk of CRC. The association persisted after adjustment for body weight at younger age and was present for both men and women, as well as for colon and rectal cancer. Differences by sex were detected for colon cancer (P for interaction = 0.003, with higher risk for men than women), but not for rectal cancer (P for interaction = 0.613). In conclusion, these data underscore the importance of body weight management from early adulthood onwards for the prevention of CRC development.

Linking diet, physical activity, cardiorespiratory fitness and obesity to serum metabolite networks: findings from a population-based study.

OBJECTIVE: It is not yet resolved how lifestyle factors and intermediate phenotypes interrelate with metabolic pathways. We aimed to investigate the associations between diet, physical activity, cardiorespiratory fitness and obesity with serum metabolite networks in a population-based study. METHODS: The present study included 2380 participants of a randomly drawn subcohort of the European Prospective Investigation into Cancer and Nutrition-Potsdam. Targeted metabolomics was used to measure 127 serum metabolites. Additional data were available including anthropometric measurements, dietary assessment including intake of whole-grain bread, coffee and cake and cookies by food frequency questionnaire, and objectively measured physical activity energy expenditure and cardiorespiratory fitness in a subsample of 100 participants. In a data-driven approach, Gaussian graphical modeling was used to draw metabolite networks and depict relevant associations between exposures and serum metabolites. In addition, the relationship of different exposure metabolite networks was estimated. RESULTS: In the serum metabolite network, the different metabolite classes could be separated. There was a big group of phospholipids and acylcarnitines, a group of amino acids and C6-sugar. Amino acids were particularly positively associated with cardiorespiratory fitness and physical activity. C6-sugar and acylcarnitines were positively associated with obesity and inversely with intake of whole-grain bread. Phospholipids showed opposite associations with obesity and coffee intake. Metabolite networks of coffee intake and obesity were strongly inversely correlated (body mass index (BMI): r = -0.57 and waist circumference: r = -0.59). A strong positive correlation was observed between metabolite networks of BMI and waist circumference (r = 0.99), as well as the metabolite networks of cake and cookie intake with cardiorespiratory fitness and intake of whole-grain bread (r = 0.52 and r = 0.50; respectively). CONCLUSIONS: Lifestyle factors and phenotypes seem to interrelate in various metabolic pathways. A possible protective effect of coffee could be mediated via counterbalance of pathways of obesity involving hepatic phospholipids. Experimental studies should validate the biological mechanisms.

Development and evaluation of a short 24-h food list as part of a blended dietary assessment strategy in large-scale cohort studies.

BACKGROUND/OBJECTIVES: The validity of dietary assessment in large-scale cohort studies has been questioned. Combining data sources for the estimation of usual intake in a blended approach may enhance the validity of dietary measurement. Our objective was to develop a web-based 24-h food list for Germany to identify foods consumed during the previous 24 h and to evaluate the performance of the new questionnaire in a feasibility study. SUBJECTS/METHODS: Available data from the German National Nutrition Survey II were used to develop a finite list of food items. A total of 508 individuals were invited to fill in the 24-h food list via the Internet up to three times during a 3-6-month time period. In addition, participants were asked to evaluate the questionnaire using a brief online evaluation form. RESULTS: In total, 246 food items were identified for the 24-h food list, reflecting >75% variation in intake of 27 nutrients and four major food groups. Among the individuals invited, 64% participated in the feasibility study. Of these, 100%, 85% and 68% of participants completed the 24-h food list one, two or three times, respectively. The average time needed to complete the questionnaire was 9 min, and its acceptability by participants was rated as high. CONCLUSIONS: The 24-h food list represents a promising new dietary assessment tool that can be used as part of a blended approach combining multiple data sources for valid estimation of usual dietary intake in large-scale cohort studies.

Variation of serum metabolites related to habitual diet: a targeted metabolomic approach in EPIC-Potsdam.

BACKGROUND/OBJECTIVE: Serum metabolites have been linked to higher risk of chronic diseases but determinants of serum metabolites are not clear. We aimed to investigate the association between habitual diet as a modifiable risk factor and relevant serum metabolites. SUBJECTS/METHODS: This cross-sectional study comprised 2380 EPIC-Potsdam participants. Intake of 45 food groups was assessed by food frequency questionnaire and concentrations of 127 serum metabolites were measured by targeted metabolomics. Reduced rank regression was used to find dietary patterns that explain the maximum variation of metabolites. RESULTS: In the multivariable-adjusted model, the proportion of explained variation by habitual diet was ranked as follows: acyl-alkyl-phosphatidylcholines (5.7%), sphingomyelins (5.1%), diacyl-phosphatidylcholines (4.4%), lyso-phosphatidylcholines (4.1%), acylcarnitines (3.5%), amino acids (2.2%) and hexose (1.6%). A pattern with high intake of butter and low intake of margarine was related to acylcarnitines, acyl-alkyl-phosphatidylcholines, lyso-phosphatidylcholines and hydroxy-sphingomyelins, particularly with saturated and monounsaturated fatty acid side chains. A pattern with high intake of red meat and fish and low intake of whole-grain bread and tea was related to hexose and phosphatidylcholines. A pattern consisting of high intake of potatoes, dairy products and cornflakes particularly explained methionine and branched chain amino acids. Dietary patterns related to type 2 diabetes-relevant metabolites included high intake of red meat and low intake of whole-grain bread, tea, coffee, cake and cookies, canned fruits and fish. CONCLUSIONS: Dietary patterns characterized by intakes of red meat, whole-grain bread, tea and coffee were linked to relevant metabolites and could be potential targets for chronic disease prevention.

Diabetes mellitus, insulin treatment, diabetes duration, and risk of biliary tract cancer and hepatocellular carcinoma in a European cohort.

BACKGROUND: Evidence on associations between self-reported diabetes mellitus, diabetes duration, age at diabetes diagnosis, insulin treatment, and risk of biliary tract cancer (BTC) and hepatocellular carcinoma (HCC), independent of general and abdominal obesity is scarce. PATIENTS AND METHODS: We conducted a prospective analysis in the EPIC-cohort study among 363 426 participants with self-reported diabetes data. Multivariable adjusted relative risks and 95% confidence intervals were estimated from Cox regression models. In a nested case-control subset, analyses were carried out in HCV/HBV-negative individuals. RESULTS: During 8.5 years of follow-up, 204 BTC cases [including 75 gallbladder cancer (GBC) cases], and 176 HCC cases were identified. Independent of body mass index and waist-to-height ratio diabetes status was associated with higher risk of BTC and HCC [1.77 (1.00-3.13) and 2.17 (1.36-3.47)]. For BTC, the risk seemed to be higher in participants with shorter diabetes duration and those not treated with insulin. Regarding cancer subsites, diabetes was only associated with GBC [2.72 (1.17-6.31)]. The risk for HCC was particularly higher in participants treated with insulin. The results were not appreciably different in HCV/HBV-negative individuals. CONCLUSION(S): This study supports the hypothesis that diabetes is a risk factor for BTC (particularly GBC) and HCC. Further research is required to establish whether diabetes treatment or duration is associated with these cancers.

General and abdominal obesity parameters and their combination in relation to mortality: a systematic review and meta-regression analysis.

Epidemiological studies assessing general and abdominal obesity measures or their combination for mortality prediction have shown inconsistent results. We aimed to systematically review the associations of body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC) and waist-to-height ratio (WHtR) with all-cause mortality in prospective cohort studies. In this systematic review, which includes a meta-regression analysis, we analysed the associations with all-cause mortality of BMI, WHR, WC and WHtR in prospective cohort studies available in Medline, Embase, the Cochrane Database of Systematic Reviews and Esbiobase from inception through 7 May 2010. A total of 18 studies met the inclusion criteria, comprising 689, 465 participants and 48, 421 deaths during 5-24 years of follow-up. The studies were heterogeneous, mainly due to differences in categorization of anthropometric parameters (AP) and different approaches to statistical analysis. Both general and abdominal obesity measures were significantly associated with mortality. In analyses using categorical variables, BMI and WC showed predominantly U- or J-shaped associations with mortality, whereas WHR and WHtR demonstrated positive relationships with mortality. All measures showed similar risk patterns for upper quantiles in comparison to reference quantiles. The parameters of general and abdominal obesity each remained significantly associated with mortality when adjusted for the other. This evidence suggests that abdominal obesity measures such as WC or WHR, show information independent to measures of general obesity and should be used in clinical practice, in addition to BMI, to assess obesity-related mortality in adults.

Smoking and the risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Smoking is not associated with prostate cancer incidence in most studies, but associations between smoking and fatal prostate cancer have been reported. METHODS: During 1992 and 2000, lifestyle information was assessed via questionnaires and personal interview in a cohort of 145,112 European men. Until 2009, 4623 incident cases of prostate cancer were identified, including 1517 cases of low-grade, 396 cases of high grade, 1516 cases of localised, 808 cases of advanced disease, and 432 fatal cases. Multivariable Cox proportional hazards regression models were used to examine the association of smoking status, smoking intensity, and smoking duration with the risk of incident and fatal prostate cancer. RESULTS: Compared with never smokers, current smokers had a reduced risk of prostate cancer (RR=0.90, 95% CI: 0.83-0.97), which was statistically significant for localised and low-grade disease, but not for advanced or high-grade disease. In contrast, heavy smokers (25+ cigarettes per day) and men who had smoked for a long time (40+ years) had a higher risk of prostate cancer death (RR=1.81, 95% CI: 1.11-2.93; RR=1.38, 95% CI: 1.01-1.87, respectively). CONCLUSION: The observation of an increased prostate cancer mortality among heavy smokers confirms the results of previous prospective studies.

Body iron stores and risk of type 2 diabetes: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study.

AIMS/HYPOTHESIS: The aim of this study was to prospectively examine the association between body iron stores and risk of type 2 diabetes. METHODS: We designed a case-cohort study among 27,548 individuals within the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study. During 7 years of follow-up, 849 incident cases of type 2 diabetes were identified. Of these, 607 remained for analyses after exclusion of participants with missing data or abnormal glucose levels at baseline. A sub-cohort of 2,500 individuals was randomly selected from the full cohort, comprising 1,969 individuals after applying the same exclusion criteria. RESULTS: After adjustment for age, sex, BMI, waist circumference, sports activity, bicycling, education, occupational activity, smoking habit, alcohol consumption and circulating levels of γ-glutamyltransferase, alanine aminotransferase, fetuin-A, high-sensitivity C-reactive protein, adiponectin, HDL-cholesterol and triacylglycerol, higher serum ferritin concentrations were associated with a higher risk of type 2 diabetes (RR in the highest vs lowest quintile, 1.73; 95% CI 1.15, 2.61; p(trend) = 0.002). No significant association was observed for soluble transferrin receptor (RR 1.33; 95% CI 0.85, 2.09; p(trend) = 0.50). The soluble transferrin receptor-to-ferritin ratio was significantly inversely related to risk (RR 0.61; 95% CI 0.41, 0.91; p(trend) = 0.02). CONCLUSIONS/INTERPRETATION: High ferritin levels are associated with higher risk of type 2 diabetes independently of established diabetes risk factors and a range of diabetes biomarkers whereas soluble transferrin receptor concentrations are not related to risk. These results support the hypothesis that higher iron stores below the level of haemochromatosis are associated with risk of type 2 diabetes.

Reliability of fasting plasma alkylresorcinol metabolites concentrations measured 4 months apart.

Alkylresorcinols (AR) have been suggested as specific dietary biomarkers of whole-grain wheat and rye intake. AR are metabolised to 3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), which have longer apparent half-lives and were recently proposed to better reflect long-term whole-grain consumption than the intact AR. The objective of this study was to analyse the reliability--expressed by the intraclass correlation coefficient (ICC)--of AR metabolite concentrations among 100 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study who provided two fasting plasma samples 4 months apart. DHBA and DHPPA concentrations were not significantly different between the first and second measurement over the 4-month period (P>0.05). The ICC was 0.32 (95% confidence interval (CI)=0.13-0.49) for DHBA and 0.37 (95%CI=0.19-0.53) for DHPPA. These results suggest that AR metabolites cannot be considered to be better biomarkers of whole-grain wheat and rye intake than the intact AR in fasting plasma (ICC=0.42).

Inflammation marker and risk of pancreatic cancer: a nested case-control study within the EPIC cohort.

BACKGROUND: Established risk factors for pancreatic cancer include smoking, long-standing diabetes, high body fatness, and chronic pancreatitis, all of which can be characterised by aspects of inflammatory processes. However, prospective studies investigating the relation between inflammatory markers and pancreatic cancer risk are scarce. METHODS: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, measuring prediagnostic blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble receptors of tumour necrosis factor-α (sTNF-R1, R2) in 455 pancreatic cancer cases and 455 matched controls. Odds ratios (ORs) were estimated using conditional logistic regression models. RESULTS: None of the inflammatory markers were significantly associated with risk of pancreatic cancer overall, although a borderline significant association was observed for higher circulating sTNF-R2 (crude OR=1.52 (95% confidence interval (CI) 0.97-2.39), highest vs lowest quartile). In women, however, higher sTNF-R1 levels were significantly associated with risk of pancreatic cancer (crude OR=1.97 (95% CI 1.02-3.79)). For sTNF-R2, risk associations seemed to be stronger for diabetic individuals and those with a higher BMI. CONCLUSION: Prospectively, CRP and IL-6 do not seem to have a role in our study with respect to risk of pancreatic cancer, whereas sTNF-R1 seemed to be a risk factor in women and sTNF-R2 might be a mediator in the risk relationship between overweight and diabetes with pancreatic cancer. Further large prospective studies are needed to clarify the role of proinflammatory proteins and cytokines in the pathogenesis of exocrine pancreatic cancer.

Association of changes in body mass index during earlier adulthood and later adulthood with circulating obesity biomarker concentrations in middle-aged men and women.

AIMS/HYPOTHESIS: The objective of our study was to investigate whether changes in BMI during earlier adulthood are more strongly associated with levels of circulating obesity biomarkers in middle age than are BMI changes during later adulthood. METHODS: The study included 1,612 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. The associations of BMI changes based on recalled BMI for the age ranges 25-40 years (earlier adulthood) and 40-55 years (later adulthood) with later biomarker levels were compared using a linear model, adjusted for BMI at age 25 years and conventional risk factors. RESULTS: BMI changes during both time periods as well as BMI at age 25 years were significantly associated with circulating levels of adiponectin, γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), high-sensitivity C-reactive protein (hs-CRP) and HDL-cholesterol (HDL-C) in both sexes, and of HbA(1c) in women. However, BMI gain for the age range 25-40 years was significantly more strongly associated with unfavourable levels of adiponectin, hs-CRP, HDL-C and HbA(1c) in men and women, and of GGT and ALT in men (p difference <0.05) than BMI gain for the age range 40-55 years. The percentage change in biomarker levels per unit gain in BMI for the age range 25-40 years ranged from 0.81% (HbA(1c)) to 9.80% (hs-CRP) in men, and from 0.75% (HbA(1c)) to 14.7% (hs-CRP) in women, whereas for the age range 40-55 years, values ranged from -0.15% to 4.82% in men and from 0.25% to 7.06% in women. CONCLUSIONS/INTERPRETATION: The results support the hypothesis that an increase in BMI in earlier adulthood is more strongly associated with unfavourable circulating levels of obesity biomarkers later in life than is an increase in BMI in later adulthood.