Janine Kröger

Healthy living is the best revenge: findings from the European Prospective Investigation Into Cancer and Nutrition-Potsdam study.

BACKGROUND Our objective was to describe the reduction in relative risk of developing major chronic diseases such as cardiovascular disease, diabetes, and cancer associated with 4 healthy lifestyle factors among German adults. METHODS We used data from 23,153 German participants aged 35 to 65 years from the European Prospective Investigation Into Cancer and Nutrition-Potsdam study. End points included confirmed incident type 2 diabetes mellitus, myocardial infarction, stroke, and cancer. The 4 factors were never smoking, having a body mass index lower than 30 (calculated as weight in kilograms divided by height in meters squared), performing 3.5 h/wk or more of physical activity, and adhering to healthy dietary principles (high intake of fruits, vegetables, and whole-grain bread and low meat consumption). The 4 factors (healthy, 1 point; unhealthy, 0 points) were summed to form an index that ranged from 0 to 4. RESULTS During a mean follow-up of 7.8 years, 2006 participants developed new-onset diabetes (3.7%), myocardial infarction (0.9%), stroke (0.8%), or cancer (3.8%). Fewer than 4% of participants had zero healthy factors, most had 1 to 3 healthy factors, and approximately 9% had 4 factors. After adjusting for age, sex, educational status, and occupational status, the hazard ratio for developing a chronic disease decreased progressively as the number of healthy factors increased. Participants with all 4 factors at baseline had a 78% (95% confidence interval [CI], 72% to 83%) lower risk of developing a chronic disease (diabetes, 93% [95% CI, 88% to 95%]; myocardial infarction, 81% [95% CI, 47% to 93%]; stroke, 50% [95% CI, -18% to 79%]; and cancer, 36% [95% CI, 5% to 57%]) than participants without a healthy factor. CONCLUSION Adhering to 4 simple healthy lifestyle factors can have a strong impact on the prevention of chronic diseases.

Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-InterAct case-cohort study

Summary Background Conflicting evidence exists regarding the association between saturated fatty acids (SFAs) and type 2 diabetes. In this longitudinal case-cohort study, we aimed to investigate the prospective associations between objectively measured individual plasma phospholipid SFAs and incident type 2 diabetes in EPIC-InterAct participants. Methods The EPIC-InterAct case-cohort study includes 12 403 people with incident type 2 diabetes and a representative subcohort of 16 154 individuals who were selected from a cohort of 340 234 European participants with 3·99 million person-years of follow-up (the EPIC study). Incident type 2 diabetes was ascertained until Dec 31, 2007, by a review of several sources of evidence. Gas chromatography was used to measure the distribution of fatty acids in plasma phospholipids (mol%); samples from people with type 2 diabetes and subcohort participants were processed in a random order by centre, and laboratory staff were masked to participant characteristics. We estimated country-specific hazard ratios (HRs) for associations per SD of each SFA with incident type 2 diabetes using Prentice-weighted Cox regression, which is weighted for case-cohort sampling, and pooled our findings using random-effects meta-analysis. Findings SFAs accounted for 46% of total plasma phospholipid fatty acids. In adjusted analyses, different individual SFAs were associated with incident type 2 diabetes in opposing directions. Even-chain SFAs that were measured (14:0 [myristic acid], 16:0 [palmitic acid], and 18:0 [stearic acid]) were positively associated with incident type 2 diabetes (HR [95% CI] per SD difference: myristic acid 1·15 [95% CI 1·09–1·22], palmitic acid 1·26 [1·15–1·37], and stearic acid 1·06 [1·00–1·13]). By contrast, measured odd-chain SFAs (15:0 [pentadecanoic acid] and 17:0 [heptadecanoic acid]) were inversely associated with incident type 2 diabetes (HR [95% CI] per 1 SD difference: 0·79 [0·73–0·85] for pentadecanoic acid and 0·67 [0·63–0·71] for heptadecanoic acid), as were measured longer-chain SFAs (20:0 [arachidic acid], 22:0 [behenic acid], 23:0 [tricosanoic acid], and 24:0 [lignoceric acid]), with HRs ranging from 0·72 to 0·81 (95% CIs ranging between 0·61 and 0·92). Our findings were robust to a range of sensitivity analyses. Interpretation Different individual plasma phospholipid SFAs were associated with incident type 2 diabetes in opposite directions, which suggests that SFAs are not homogeneous in their effects. Our findings emphasise the importance of the recognition of subtypes of these fatty acids. An improved understanding of differences in sources of individual SFAs from dietary intake versus endogenous metabolism is needed. Funding EU FP6 programme, Medical Research Council Epidemiology Unit, Medical Research Council Human Nutrition Research, and Cambridge Lipidomics Biomarker Research Initiative.

Erythrocyte membrane phospholipid fatty acids, desaturase activity, and dietary fatty acids in relation to risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam Study

BACKGROUND The long-term role of fatty acids (FAs) in the cause of diabetes remains largely unclear. OBJECTIVE We aimed to investigate erythrocyte membrane FAs, desaturase activity, and dietary FAs in relation to the incidence of type 2 diabetes. DESIGN We applied a nested case-cohort design (n = 2724, including 673 incident diabetes cases) within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study, which involves 27,548 middle-aged subjects. Thirty erythrocyte membrane FAs (percentage of total FAs) and FA intake (percentage of total fat) were measured at baseline, and physician-confirmed incident diabetes was assessed during a mean follow-up of 7.0 y. We evaluated Δ⁵ desaturase (D5D) and Δ⁶ desaturase (D6D) activity by using FA product-to-precursor ratios (traditional approach) and by investigating variants in FADS1 and FADS2 genes that encode these desaturases (Mendelian randomization approach). RESULTS As a main finding, erythrocyte 16:1n-7 and 18:3n-6 and FA ratios, which reflect stearoyl coenzyme A desaturase (SCD) and D6D activity, were directly related to diabetes risk in multivariable-adjusted models [relative risks (95% CIs) comparing extreme quintiles: 16:1n-7, 2.11 (1.46, 3.05); 18:3n-6, 2.00 (1.38, 2.88); SCD, 2.61 (1.75, 3.89); and D6D, 2.46 (1.67, 3.63)], whereas the FA ratio that reflects D5D activity was inversely associated with risk [0.46 (0.31, 0.70)]. The Mendelian randomization approach corroborated the direct relation for D6D activity and tended to support the inverse relation for D5D activity. Proportions of dietary FAs showed only modest to low correlations with erythrocyte FAs and were not significantly associated with risk. CONCLUSION The FA profile of erythrocyte membrane phospholipids and activity of desaturase enzymes are strongly linked to the incidence of type 2 diabetes.

The Association between Diet and Serum Concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 in the European Prospective Investigation into Cancer and Nutrition

Circulating concentrations of insulin-like growth factor I (IGF-I) and IGF binding proteins (IGFBP) have been associated with the risk of several types of cancer. Dietary correlates of IGF-I and IGFBPs are not yet well established. The objective of this study was to assess the association between dietary intake and serum concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 in a cross-sectional analysis of 4,731 men and women taking part in the European Prospective Investigation into Cancer and Nutrition. Diet was assessed using country-specific validated dietary questionnaires. Serum concentrations of IGF-I, IGFBP-1, IGFBP-2 and IGFBP-3 were measured, and the associations between diet and IGF-I and IGFBPs were assessed using multiple linear regression adjusting for sex, age, body mass index, smoking status, and alcohol and energy intake. Each 1 SD increment increase in total and dairy protein and calcium intake was associated with an increase in IGF-I concentration of 2.5%, 2.4%, and 3.3%, respectively (P for trend <0.001 for all) and a decrease in IGFBP-2 of 3.5%, 3.5%, and 5.4% (P for trend <0.001 for all), respectively. There were no significant associations between the intake of protein or calcium from nondairy sources and IGF-I. The results from this large cross-sectional analysis show that either the intake of dairy protein or calcium is an important dietary determinant of IGF-I and IGFBP-2 concentrations; however, we suggest that it is more likely to be protein from dairy products. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1333–40)

Serum Vitamin D and Risk of Prostate Cancer in a Case-Control Analysis Nested Within the European Prospective Investigation into Cancer and Nutrition (EPIC)

Results from the majority of studies show little association between circulating concentrations of vitamin D and prostate cancer risk, a finding that has not been demonstrated in a wider European population, however. The authors examined whether vitamin D concentrations were associated with prostate cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (1994–2000). Serum concentrations of 25-hydroxyvitamin D were measured in 652 prostate cancer cases matched to 752 controls from 7 European countries after a median follow-up time of 4.1 years. Conditional logistic regression models were used to calculate odds ratios for prostate cancer risk in relation to serum 25-hydroxyvitamin D after standardizing for month of blood collection and adjusting for covariates. No significant association was found between 25-hydroxyvitamin D and risk of prostate cancer (highest vs. lowest quintile: odds ratio = 1.28, 95% confidence interval: 0.88, 1.88; P for trend = 0.188). Subgroup analyses showed no significant heterogeneity by cancer stage or grade, age at diagnosis, body mass index, time from blood collection to diagnosis, or calcium intake. In summary, the results of this large nested case-control study provide no evidence in support of a protective effect of circulating concentrations of vitamin D on the risk of prostate cancer.

Region-Specific Nutrient Intake Patterns Exhibit a Geographical Gradient within and between European Countries

Until recently, the study of nutrient patterns was hampered at an international level by a lack of standardization of both dietary methods and nutrient databases. We aimed to describe the diversity of nutrient patterns in the European Prospective Investigation into Cancer and Nutrition (EPIC) study at population level as a starting point for future nutrient pattern analyses and their associations with chronic diseases in multi-center studies. In this cross-sectional study, 36,034 persons aged 35-74 y were administered a single, standardized 24-h dietary recall. Intake of 25 nutrients (excluding intake from dietary supplements) was estimated using a standardized nutrient database. We used a graphic presentation of mean nutrient intakes by region and sex relative to the overall EPIC means to contrast patterns within and between 10 European countries. In Mediterranean regions, including Greece, Italy, and the southern centers of Spain, the nutrient pattern was dominated by relatively high intakes of vitamin E and monounsaturated fatty acids (MUFA), whereas intakes of retinol and vitamin D were relatively low. In contrast, in Nordic countries, including Norway, Sweden, and Denmark, reported intake of these same nutrients resulted in almost the opposite pattern. Population groups in Germany, The Netherlands, and the UK shared a fatty acid pattern of relatively high intakes of PUFA and SFA and relatively low intakes of MUFA, in combination with a relatively high intake of sugar. We confirmed large variability in nutrient intakes across the EPIC study populations and identified 3 main region-specific patterns with a geographical gradient within and between European countries.

Recent insights into the relation of Δ5 desaturase and Δ6 desaturase activity to the development of type 2 diabetes.

Purpose of review The &Dgr;5 desaturase (D5D) and &Dgr;6 desaturase (D6D) are key enzymes in the metabolism of polyunsaturated fatty acids. This review aims to summarize recent advances towards understanding the relation of the activities of D5D and D6D to the development of type 2 diabetes. Recent findings Prospective studies that investigated fatty acid product-to-precursor ratios in blood as estimates of desaturase activity reported a clear inverse relation of D5D activity and a strong direct relation of D6D activity to diabetes incidence. Due to the prospective design and comprehensive confounder adjustment in these studies, confounding and reverse causation are unlikely explanations for these findings. Furthermore, studies on genetic variation in the FADS1 and FADS2 genes, which encode D5D and D6D, also point to an influence of D5D and D6D activity on glucose metabolism. The inverse relation of D5D activity and the direct relation of D6D activity to diabetes risk have been corroborated by a Mendelian randomization approach recently. Summary These recent studies suggest an important role of D5D and D6D activities for the development of type 2 diabetes. Factors which influence the activities of these desaturases are likely to be of public health relevance.

Television watching and incident diabetes: Findings from the European Prospective Investigation into Cancer and Nutrition–Potsdam Study*

Background:  The aim of the present study was to examine whether the amount of time spent watching television is a potential risk factor for incident diabetes and to what extent this association may be explained by obesity.

Genetic variation of the FADS1 FADS2 gene cluster and n-6 PUFA composition in erythrocyte membranes in the European Prospective Investigation into Cancer and Nutrition-Potsdam study.

Delta-5 (D5D) and delta-6 (D6D) desaturases are key enzymes in PUFA metabolism. Several factors (e.g. hyperglycaemia, hypertension, blood lipids, statins and fatty acids in diet and biological tissues) may influence desaturase activity. The goals were to evaluate the associations between variation in genes encoding these desaturases (FADS1 and FADS2) and blood concentrations of n-6 PUFA and estimated D5D and D6D activities (evaluated as product/precursor ratio), and to investigate whether other factors influencing the activity of desaturases modify these associations. A random sample of 2066 participants from the European Prospective Investigation into Cancer and Nutrition-Potsdam study (n 27 548) was utilised in the analyses. Crude and adjusted associations between rs174546 genotypes (reflecting genetic variation in the FADS1 FADS2 gene cluster), n-6 PUFA in erythrocytes and estimated desaturase activities were evaluated using multiple linear regression. Potential effect modification was determined by performing stratified analyses and evaluating interaction terms. We found rs174546 genotypes to be related to linoleic (r² 0·060), γ-linolenic (r² 0·041), eicosadienoic (r² 0·034), arachidonic (r² 0·026), docosatetraenoic acids (r² 0·028), estimated D6D activity (r² 0·052) and particularly strongly to dihomo-γ-linolenic acid (DGLA, r² 0·182) and D5D activity (r² 0·231). We did not observe effect modifications with regard to the estimated D5D activity, DGLA and arachidonic acid (AA) for most of the factors evaluated; however, the genetic effect on D5D activity and DGLA may be modified by the dietary n-6:n-3-ratio (P-values for interaction: 0·008 and 0·002), and the genetic effect on DGLA and AA may be modified by lipid-lowering medication (P-values for interaction: 0·0004 and 0·006). In conclusion, genetic variation in the FADS1 FADS2 gene cluster affects n-6 PUFA profiles in erythrocytes reflecting altered D5D activity.

Body adiposity index, body fat content and incidence of type 2 diabetes

Aims/hypothesisThe aim of this study was to compare estimates of body fat content, i.e. body adiposity index (BAI), BMI and waist and hip circumferences, with respect to their ability to predict the percentage of body fat (PBF; confirmed by magnetic resonance tomography) and incident type 2 diabetes.MethodsAssociations between anthropometric measurements and PBF were evaluated in the Tübingen Lifestyle Intervention Program (TULIP; 138 men, 222 women), and between these measurements and incident type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study (9,729 men, 15,438 women) and the Cooperative Health Research in the Region of Augsburg (KORA) study (5,573 men, 5,628 women), using correlation and multivariate Cox regression analyses.ResultsBMI more strongly correlated with PBF (men: r = 0.81, women: r = 0.84) than BAI (r = 0.68 and 0.81, respectively), while waist circumference among men (r = 0.84) and hip circumference among women (r = 0.88) showed the strongest correlations. BAI overestimated PBF among men (mean difference −3.0%), and this error was dependent on the value of PBF. BAI was more weakly associated with diabetes risk (RRs for 1 SD, EPIC-Potsdam men: 1.62 [95% CI 1.52, 1.72], women: 1.67 [95% CI 1.55, 1.80]; KORA men: 1.62 [95% CI 1.48, 1.78], women: 1.82 [95% CI 1.65, 2.02]) compared with BMI (RRs, EPIC-Potsdam men: 1.95 [95% CI 1.83, 2.09], women 1.88 [95% CI 1.76, 2.02], KORA men 1.75 [95% CI 1.62, 1.89], women 2.00 [95% CI 1.81, 2.22]), while waist circumference showed the strongest associations (RRs: 2.17 [95% CI 2.01, 2.35], 2.33 [95% CI 2.15, 2.53], 1.81 [95% CI 1.66, 1.96] and 2.29 [95% CI 2.05, 2.57] for EPIC-Potsdam men and women and KORA men and women, respectively).Conclusions/interpretationWaist circumference in men and hip circumference in women are better predictors of PBF than BAI and BMI. BAI was not as strong a predictor of diabetes as BMI, while waist circumference was the strongest predictor.