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Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Grant from the German Federal Ministry of Education and Research (Bundesministerium fuer Bildung und Forschung) to the German Center for Diabetes Research (DZD grant 82DZD00302), Joint Programming Initiative A Healthy Diet for a Healthy Life, as part of the ERA-HDHL cofounded joint call Biomarkers for Nutrition and Health (01EA1704). Background Deep lipidomics might more accurately capture metabolic effects of dietary interventions that aim to modulate the fat quality of the habitual diet compared to standard risk markers. We generated a multi-lipid score (MLS) to summarize the effect of a dietary intervention aiming to substitute saturated with unsaturated fats and assessed its association with incident cardiometabolic diseases. Methods The Dietary Intervention and VAScular function study (DIVAS) was a 16-week, randomized, controlled parallel unsaturated-for-saturated fat substitution (8% total energy, Figure 1A) trial in hundred-thirteen men and women. In regression models, we examined the diet effect on single lipids and combined the significantly affected lipids (P Results The DIVAS unsaturated fat-rich diet reduced lipid metabolites with medium or long-chain fatty acid residuals containing no or few unsaturations in ceramides, cholesterol esters, diglycerides, and phospholipids, which we combine in the MLS (Figure 1B/C). Aside from the MLS, only non-high-density lipoprotein cholesterol (non-HDL-C) was significantly affected in the diet (Figure 1D). In multivariable adjusted models, the MLS, scaled to the observed change in DIVAS (i.e. the theoretical intervention effect), was strongly associated with reduced risk for incident CVD and T2D (Figure 2A). Further adjustment for established risk markers did not meaningfully alter the association, with the exception of the association with T2D and adjustment for plasma triglycerides. Translated to a hypothetical effect on case occurrence, the DIVAS diet intervention-induced MLS difference was associated with markedly fewer CVD (32%, 95%-CI: 21% to 42%) cases and T2D (26%, 95%-CI: 15% to 35%) cases in EPIC-Potsdam (Figure 2B). In contrast, initially observed associations of non-HDL-C, the only other intervention-affected marker, were attenuated when adjusting for the MLS. Conclusion Capturing diet effects using lipidomics profiling, as we show with the generated MLS, might provide superior biomarkers to monitor cardiometabolic benefits of changes to dietary fat quality.

Metabolic alterations precede cardiometabolic disease onset. Here we present ceramide- and dihydroceramide-profiling data from a nested case-cohort (type 2 diabetes [T2D, n = 775]; cardiovascular disease [CVD, n = 551]; random subcohort [n = 1137]) in the prospective EPIC-Potsdam study. We apply the novel NetCoupler-algorithm to link a data-driven (dihydro)ceramide network to T2D and CVD risk. Controlling for confounding by other (dihydro)ceramides, ceramides C18:0 and C22:0 and dihydroceramides C20:0 and C22:2 are associated with higher and ceramide C20:0 and dihydroceramide C26:1 with lower T2D risk. Ceramide C16:0 and dihydroceramide C22:2 are associated with higher CVD risk. Genome-wide association studies and Mendelian randomization analyses support a role of ceramide C22:0 in T2D etiology. Our results also suggest that (dh)ceramides partly mediate the putative adverse effect of high red meat consumption and benefits of coffee consumption on T2D risk. Thus, (dihydro)ceramides may play a critical role in linking genetic predisposition and dietary habits to cardiometabolic disease risk.

Nach Schatzungen der International Diabetes Federation hatten im Jahr 2011 366 Mio. Personen im Alter zwischen 20 und 79 Jahren weltweit einen Diabetes mellitus.

OBJECTIVE To study the association between adherence to the Mediterranean dietary pattern (MDP) and risk of developing type 2 diabetes, across European countries. RESEARCH DESIGN AND METHODS We established a case-cohort study including 11,994 incident type 2 diabetic case subjects and a stratified subcohort of 15,798 participants selected from a total cohort of 340,234 participants with 3.99 million person-years of follow-up, from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The relative Mediterranean diet score (rMED) (score range 0–18) was used to assess adherence to MDP on the basis of reported consumption of nine dietary components characteristic of the Mediterranean diet. Cox proportional hazards regression, modified for the case-cohort design, was used to estimate the association between rMED and risk of type 2 diabetes, adjusting for confounders. RESULTS The multiple adjusted hazard ratios of type 2 diabetes among individuals with medium (rMED 7–10 points) and high adherence to MDP (rMED 11–18 points) were 0.93 (95% CI 0.86–1.01) and 0.88 (0.79–0.97), respectively, compared with individuals with low adherence to MDP (0–6 points) (P for trend 0.013). The association between rMED and type 2 diabetes was attenuated in people

Objectives:To investigate whether dietary glycaemic index (GI) and glycaemic load (GL) were associated with subsequent weight and waist circumference change.Design:Population-based prospective cohort study.Setting:Five European countries, which are Denmark, Germany, Italy, The Netherlands and the United Kingdom.Participants:A total of 89 432 participants, aged 20-78 years (mean =53 years) at baseline and followed for 1.9-12.5 years (mean=6.5 years). All participants were free of self-reported cancer, cardiovascular diseases and diabetes at baseline.Methods:Glycaemic index and GL were calculated on the basis of dietary intake assessed by food frequency questionnaires and by using a GI table developed for this study with published GI values as the main sources. Anthropometric data were collected both at baseline and at the end of follow-up. Multiple linear regression analyses were conducted in each centre and random-effect meta-analyses were used to combine the effects. Adjustment was made for baseline anthropometrics, demographic and lifestyle factors, follow-up duration and other dietary factors.Results:Mean GI and GL were 57 and 134, respectively. Associations of GI and GL with subsequent changes of weight and waist circumference were heterogeneous across centres. Overall, with every 10-unit higher in GI, weight increased by 34 g per year (95% confidence interval (CI): -47, 115) and waist circumference increased by 0.19 cm per year (95% CI: 0.11, 0.27). With every 50-unit higher in GL, weight increased by 10 g per year (95% CI: -65, 85) and waist circumference increased by 0.06 cm per year (95% CI: -0.01, 0.13).Conclusions:Our findings do not support an effect of GI or GL on weight change. The positively significant association between GI, not GL, and subsequent gain in waist circumference may imply a beneficial role of lower GI diets in the prevention of abdominal obesity. However, further studies are needed to confirm this finding given the small effect observed in this study.International Journal of Obesity advance online publication, 25 August 2009; doi:10.1038/ijo.2009.163.

The German Diabetes Risk Score (DRS) was developed at the German Institute of Human Nutrition from data of the European Prospective Investigation into Cancer and Nutrition (EPIC-Potsdam) in order to estimate the 5-year probability of developing type 2 diabetes, based on anthropometric measures and lifestyle as well as diet information. This study evaluated associations between the DRS and metabolic risk factors of type 2 diabetes for the purpose of further validating the risk score.2500 participants of the EPIC-Potsdam study were randomly selected, and glucose, HbA1c, triglycerides, HDL cholesterol, hs-C-reactive protein, and gamma-glutamyltransferase were determined. After exclusion of participants with known diabetes (n = 120), those for whom not all biomarkers could be determined (n = 92) and those with elevated plasma glucose concentrations (random glucoseor= 200 mg/dl or fasting glucoseor= 126 mg/dl, n = 9) or with low plasma glucose concentrations (50 mg/dl, n = 38), the data on 2223 participants (839 men and 1384 women) remained for analysis of which 640 (252 men and 388 women) were fasting at the time blood samples had been obtained.The DRS significantly correlated with all biomarkers (p0.001). Pearson correlation coefficients ranged from 0.25 for glucose and 0.45 for triglycerides. While glucose, HbA (1c), triglycerides, hs-CRP and gamma-glutamyltransferase increased with increasing DRS points, HDL cholesterol was inversely associated. The mean concentrations of glucose, HbA (1c) and triglycerides for persons with300 DRS points were 83 mg/dl, 6.2 % und 62 mg/dl. In contrast, mean concentrations were 100 mg/dl for glucose, 6,9 % HbA (1c) und 171 mg/dl triglycerides among participants withor= 700 DRS points. HDL cholesterol was considerably lower (37.6 mg/dl) among participants withor= 700 DRS points than those with300 DRS points (55 mg/dl). There were also considerable differences in biomarker concentrations for hs-CRP and gamma-glutamyltransferase in relation to the DRS. Associations were generally similar for men and women.Our data suggest that the DRS allows to detect persons with prediabetes with high sensitivity and specificity. Thus the DRS could be used as a routine medical checkup in programs for the prevention of type 2 diabetes.

The first part of this paper outlined terms and definitions in the context of the application of biological markers in epidemiological studies. Cardiovascular epidemiology served as an example for their historical development. The second part focusses on DNA-based biomarkers, practical and methodological dimensions of the use of biomarkers in analytic epidemiological studies as well as requirements in respect of validity and quality assurance. Most genetic polymorphisms have no impact on health. However, some can be used as biomarkers for individual sensitvity to exposures and susceptibility for specific diseases. The Human Genome Project has brought about a quantum leap in the development of genetic markers. The practical implications cannot presently be assessed with certainty. However, present and future research programmes of gene-environment interactions depend on "traditional" epidemiological study designs, methods, and concepts. Ethical principles and data protection requirements apply equally to genetic and molecular epidemiology as do the "Guidelines for Good Epidemiological Practice".

Currently, substantial variation in epidemiologic studies exists regarding the number of blood pressure (BP) readings obtained and the way in which they are combined. This might result in systematically different BP estimates. We therefore analysed data from 25,891 subjects (10,124 men and 15,767 women) of the EPIC-Potsdam Study (European Prospective Investigation into Cancer and Nutrition) to estimate the magnitude of differences between consecutive BP readings and their combinations. Three measurements with 2 min intervals were performed in the sitting position on the right arm with the supported arm elevated at heart level by trained interviewers using oscillometric devices. Mean BP declined from first to second reading and further to third reading by systolic 5.0/0.9 mmHg in men and 4.9/0.8 mmHg in women and by diastolic 1.5/0.3 mmHg in men and 1.9/0.5 mmHg in women, as well as pulse pressure (PP) (3.5/0.6 in men, 3.0/0.3 in women) and hypertension prevalence (9.1/1.7%-points). The magnitude of BP decline depended on BP level, age, body mass index (BMI), and BP medication. Combinations including the first reading lead to generally higher estimates than subsequent readings or their combination. Published data on mean BP, PP and hypertension prevalence depend on the number and subsequent handling of BP readings which might introduce bias to the comparison of different studies unless the same defined readings were used. The combination of the second and third reading seems to be favourable over any single reading or other combinations.

In the baseline assessment of the two EPIC-Germany cohorts Heidelberg and Potsdam, dietary information was obtained with an identical food frequency questionnaire (FFQ). The optically readable FFQ was designed to assess the usual food and nutrient intake of individuals during the past 12 months. The present analysis was based on dietary data from 25,212 participants in Heidelberg (11,776 men, 13,436 women) and 26,270 participants in Potsdam (10,249 men, 16,021 women). This paper presents the first results of a descriptive dietary analysis on a food group level based on 16 food groups and selected subgroups. Each of these food groups and subgroups was divided into quintiles, and the age-adjusted mean intake for each quintile was calculated. The comparison of dietary habits between the two cohorts, as well as the comparison between men and women within each cohort showed clear differences both in the quintiles of most food groups as well as in the range between the lowest and highest quintile. Except for the food groups non-alcoholic and alcoholic beverages, sugar and confectionery, sauces, and soups, men and women participating in Potsdam reported higher intakes of all the other food groups. The amount of food intake was generally lower in women than in men, with the exception of vegetables, fruit, dairy products, and non-alcoholic beverages. Further differences between the study centers were observed regarding the use of cooking fat for meat and vegetable preparation. In conclusion, the dietary variation, e.g. the exposure variation, was increased by recruiting two geographically distinct cohorts, instead of only one, in Germany.

The EPIC-Heidelberg and the EPIC-Potsdam studies with about 53,000 study participants represent the German contribution to the EPIC (European Investigation into Cancer and Nutrition) cohort study. Within the EPIC study, standardized 24-hour dietary recalls were applied as a quantitative calibration method in order to estimate the amount of scaling bias introduced by the varying center-specific dietary assessment methods. This article presents intake of food items and food groups in the two German cohorts estimated by 24-hour quantitative dietary recalls. Recalls from 1,013 men and 1,078 women in Heidelberg and 1,032 men and 898 women in Potsdam were included in the analysis. The intake of recorded food items or recipe ingredients as well as fat used for cooking was summarized into 16 main food groups and a variety of different subgroups stratified by sex and weighted for the day of the week and age. In more than 90% of the recalls, consumption of dairy products, cereals and cereal products, bread, fat, and non-alcoholic beverages, particularly coffee/tea, was reported. Inter-cohort evaluations revealed that bread, potatoes, fruit and fat were consumed in higher amounts in the Potsdam cohort while the opposite was found for pasta/rice, non-alcoholic, and alcoholic beverages. It was concluded that the exposure variation was increased by having two instead of one EPIC study centers in Germany.