Dagmar Drogan - Academia.edu (original) (raw)

Papers by Dagmar Drogan

Clinical chemistry, Jan 18, 2014

Application of metabolite profiling could expand the etiological knowledge of type 2 diabetes mel... more Application of metabolite profiling could expand the etiological knowledge of type 2 diabetes mellitus (T2D). However, few prospective studies apply broad untargeted metabolite profiling to reveal the comprehensive metabolic alterations preceding the onset of T2D. We applied untargeted metabolite profiling in serum samples obtained from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort comprising 300 individuals who developed T2D after a median follow-up time of 6 years and 300 matched controls. For that purpose, we used ultra-performance liquid chromatography-mass spectrometry with a protocol specifically designed for large-scale metabolomics studies with regard to robustness and repeatability. After multivariate classification to select metabolites with the strongest contribution to disease classification, we applied multivariable-adjusted conditional logistic regression to assess the association of these metabolites with T2D. Among several alt...

Public Health Nutrition, 2006

Objective: To assess the relationship between intake of dietary folate equivalents and risk of my... more Objective: To assess the relationship between intake of dietary folate equivalents and risk of myocardial infarction in a German cohort. Design: Intake of dietary folate equivalents was assessed by a validated foodfrequency questionnaire. Cox proportional hazard models were used to evaluate the association between intake of dietary folate equivalents and risk of myocardial infarction. Setting: The European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, Germany. Subjects: Subjects were 22 245 apparently healthy non-users of vitamin supplements aged 35-64 years. Results: During 4.6 years of follow-up, 129 incident cases of myocardial infarction were identified. Compared with intake below the median (103 mg), higher intake of dietary folate equivalents was associated with a multivariate-adjusted hazard ratio (HR) of 0.57 (95% confidence interval (CI) 0.36-0.91). The inverse association of folate intake and myocardial infarction risk was stronger in participants with an ethanol intake equal to or above the sex-specific median (HR ¼ 0.37, 95% CI 0.18-0.79) and attenuated in those with a low ethanol intake (HR ¼ 0.67, 95% CI 0.37-1.22). Conclusion: An increased intake of dietary folate equivalents was observed to be associated with decreased risk of myocardial infarction in a German study population, pointing towards the importance of folate intake with respect to primary prevention of myocardial infarction.

Arteriosclerosis, Thrombosis, and Vascular Biology, 2010

Objective— To investigate the interrelation between plasma γ-glutamyltransferase (GGT) activity, ... more Objective— To investigate the interrelation between plasma γ-glutamyltransferase (GGT) activity, cysteinyl-glycine (Cys-Gly) (ie, a thiol originating from GGT-mediated cleavage of glutathione), and oxidized low-density lipoprotein (oxLDL) with regard to myocardial infarction (MI) risk in a prospective study. Methods and Results— Incident cases of MI were identified among European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam participants without prior MI during 6.0 years of follow-up. Baseline levels of Cys-Gly and oxLDL and GGT activity in plasma were measured in a case-cohort study comprising 837 subjects without incident MI and 116 subjects with incident MI. The relation of GGT, Cys-Gly and oxLDL to MI risk was assessed using Cox proportional hazards regression analysis. After adjustment for established risk factors, hazard ratios associated with a 1-SD unit increase in the log-transformed biomarker were 1.63 (95% CI, 1.30 to 2.05) for GGT, 1.36 (95% CI, 1.07...

Chocolate consumption in relation to blood pressure and risk of cardiovascular disease

Aims To investigate the association of chocolate consumption with measured blood pressure (BP) an... more Aims To investigate the association of chocolate consumption with measured blood pressure (BP) and the incidence of cardiovascular disease (CVD). Methods and results Dietary intake, including chocolate, and BP were assessed at baseline (1994-98) in 19 357 participants (aged 35-65 years) free of myocardial infarction (MI) and stroke and not using antihypertensive medication of the Potsdam arm of the European Prospective Investigation into Cancer and Nutrition. Incident cases of MI (n ¼ 166) and stroke (n ¼ 136) were identified after a mean follow-up of 8 years. Mean systolic BP was 1.0 mmHg [95% confidence interval (CI) 21.6 to 20.4 mmHg] and mean diastolic BP 0.9 mmHg (95% CI 21.3 to 20.5 mmHg) lower in the top quartile compared with the bottom quartile of chocolate consumption. The relative risk of the combined outcome of MI and stroke for top vs. bottom quartiles was 0.61 (95% CI 0.44-0.87; P linear trend ¼ 0.014). Baseline BP explained 12% of this lower risk (95% CI 3-36%). The inverse association was stronger for stroke than for MI. Conclusion Chocolate consumption appears to lower CVD risk, in part through reducing BP. The inverse association may be stronger for stroke than for MI. Further research is needed, in particular randomized trials.

Revue d'Épidémiologie et de Santé Publique, 2018

Obesity Facts, 2019

Background: Adipokines are hormones secreted from adipose tissue (AT), and a number of them have ... more Background: Adipokines are hormones secreted from adipose tissue (AT), and a number of them have been established as risk factors for chronic diseases. However, it is not clear whether and to what extent adiposity, gene expression, and other factors determine their circulating levels. Objectives: To assess to what extent adiposity, as measured by the amount of subcutaneous AT (SAT) and visceral AT (VAT) using magnetic resonance imaging, and gene expression levels in SAT determine plasma concentrations of the adipokines adiponectin, leptin, soluble leptin receptor, resistin, interleukin 6, and fatty acid-binding protein 4 (FABP4). Methods: We performed a cross-sectional analysis of 156 participants from the EPIC Potsdam cohort study and analyzed multiple regression models and partial correlation coefficients. Results: For leptin and FABP4 concentrations, 81 and 45% variance were explained by SAT mass, VAT mass, and gene expression in SAT in multivariable regression models. For the re...

The Journal of Clinical Endocrinology & Metabolism, 2019

Context: Adipocyte fatty acid-binding protein (FABP4) is expressed in adipose tissue and may impa... more Context: Adipocyte fatty acid-binding protein (FABP4) is expressed in adipose tissue and may impair glucose homeostasis and promote atherosclerotic processes. Objective: We examined the association between serum FABP4 and risk of type 2 diabetes (T2D), myocardial infarction (MI), and stroke. Design: Case-cohort study embedded within a sample of 27,548 participants of the EPIC-Potsdam cohort. Participants and Setting: A randomly selected subcohort (n 5 2194) of participants who were free of cardiovascular disease and T2D at study baseline and 728 incident T2D cases, 206 incident stroke cases, and 185 incident MI cases with an average 8.2 (61.7) years of follow-up. Main Outcome Measures: Incident T2D, MI, and stroke. Results: In a multivariable-adjusted model, the hazard ratios (HRs) in the highest vs lowest quartile of FABP4 were 1.81 (95% CI, 1.21 to 2.70; P trend 5 0.01) for T2D, 0.93 (95% CI, 0.55 to 1.55; P trend 5 0.68) for MI, and 1.41 (95% CI, 0.80 to 2.49; P trend 5 0.24) for stroke, respectively. In analyses stratified by sex, no statistically significant differences could be seen for associations between FABP4 and T2D and MI (P interaction by sex 5 0.27 and 0.84, respectively), whereas a higher risk of stroke was observed in men

The Journal of Nutrition, 2007

Recently, a food pattern predictive for prospective weight change was identified within the Europ... more Recently, a food pattern predictive for prospective weight change was identified within the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort. Given the possible impact of weight change on cardiovascular disease (CVD) risk, we examined the association between the above mentioned food pattern and risk of CVD. The analyzed food pattern was defined by a high consumption of whole-grain bread, fruits, fruit juices, grain flakes and/or cereals, and raw vegetables, and a low consumption of processed meat, butter, high-fat cheese, margarine, and meat other than poultry. The associations between quartiles of the food pattern score and CVD morbidity and mortality were examined in 26,238 subjects of the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort using a Cox's Proportional Hazards model for competing risks. During 6.4 y of follow-up, 379 incident cases of CVD were identified, of which 68 were fatal events. The food pattern was not associated with risk of nonfatal CVD. After adjusting for cardiovascular risk factors, the hazard ratios for fatal CVD across increasing quartiles of the score were 1.00, 0.85, 0.31, and 0.47, respectively (P for trend ¼ 0.016). The association of the food pattern with CVD risk differed between fatal and nonfatal events (P for difference ¼ 0.05). These findings from a large German cohort indicate that a food pattern predicting prospective weight change may be associated with the risk of fatal CVD.

International Journal of Epidemiology, 2016

Background: The application of metabolomics in prospective cohort studies is statistically challe... more Background: The application of metabolomics in prospective cohort studies is statistically challenging. Given the importance of appropriate statistical methods for selection of diseaseassociated metabolites in highly correlated complex data, we combined random survival forest (RSF) with an automated backward elimination procedure that addresses such issues. Methods: Our RSF approach was illustrated with data from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, with concentrations of 127 serum metabolites as exposure variables and time to development of type 2 diabetes

American Journal of Epidemiology, 2008

After screening out inappropriate or doubtful covariates on the basis of background knowledge, on... more After screening out inappropriate or doubtful covariates on the basis of background knowledge, one may still be left with many potential confounders. It is then tempting to use statistical variable-selection methods to reduce the number used for adjustment. Nonetheless, there is no agreement on how selection should be conducted, and it is well known that conventional selection methods lead to confidence intervals that are too narrow and p values that are too small. Furthermore, theory and simulation evidence have found no selection method to be uniformly superior to adjusting for all well-measured confounders. Nonetheless, control of all measured confounders can lead to problems for conventional model-fitting methods. When these problems occur, one can apply modern techniques such as shrinkage estimation, exposure modeling, or hybrids that combine outcome and exposure modeling. No selection or special software is needed for most of these techniques. It thus appears that statistical confounder selection may be an unnecessary complication in most regression analyses of effects.

Nutrition & diabetes, 2015

Obesity may be related to differential DNA methylation and thus to differential expression of key... more 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 anthropomet...

PLoS ONE, 2012

Objective: First, to investigate and compare associations between alcohol consumption and variant... more Objective: First, to investigate and compare associations between alcohol consumption and variants in alcohol dehydrogenase (ADH) genes with incidence of cardiovascular diseases (CVD) in a large German cohort. Second, to quantitatively summarize available evidence of prospective studies on polymorphisms in ADH1B and ADH1C and CVD-risk. Methods: We conducted a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort including a randomly drawn subcohort (n = 2175) and incident cases of myocardial infarction (MI; n = 230) or stroke (n = 208). Mean follow-up time was 8.262.2 years. The association between alcohol consumption, ADH1B or ADH1C genotypes, and CVD-risk was assessed using Cox proportional hazards regression. Additionally, we report results on associations of variants in ADH1B and ADH1C with ischemic heart disease and stroke in the context of a meta-analysis of previously published prospective studies published up to November 2011. Results: Compared to individuals who drank .0 to 6 g alcohol/d, we observed a reduced risk of MI among females consuming .12 g alcohol/d (HR = 0.31; 95% CI: 0.10-0.97) and among males consuming .24 to 60 g/d (HR = 0.57; 95% CI: 0.33-0.98) or .60 g alcohol/d (HR = 0.30; 95% CI: 0.12-0.78). Stroke risk was not significantly related to alcohol consumption .6 g/d, but we observed an increased risk of stroke in men reporting no alcohol consumption. Individuals with the slowcoding ADH1B*1/1 genotype reported higher median alcohol consumption. Yet, polymorphisms in ADH1B or ADH1C were not significantly associated with risk of CVD in our data and after pooling results of eligible prospective studies [ADH1B*1/1: RR = 1.35 (95% CI: 0.98-1.88; p for heterogeneity: 0.364); ADH1C*2/2: RR = 1.07 (95% CI: 0.90-1.27; p for heterogeneity: 0.098)]. Conclusion: The well described association between alcohol consumption and CVD-risk is not reflected by ADH polymorphisms, which modify the rate of ethanol oxidation.

The American Journal of Clinical Nutrition, 2014

Background: The inverse association between coffee consumption and the risk of type 2 diabetes (T... more Background: The inverse association between coffee consumption and the risk of type 2 diabetes (T2D) is well established; however, little is known about potential mediators of this association. Objective: We aimed to investigate the association between coffee consumption and diabetes-related biomarkers and their potential role as mediators of the association between coffee consumption and T2D. Design: We analyzed a case-cohort study (subcohort: n = 1610; verified incident T2D cases: n = 417) nested within the European Prospective Investigation into Cancer and Nutrition-Potsdam study involving 27,548 middle-aged participants. Habitual coffee consumption was assessed with a validated, semiquantitative food-frequency questionnaire. We evaluated the association between coffee consumption and several T2D-related biomarkers, such as liver markers (reflected by g-glutamyltransferase, fetuin-A, and sex hormone-binding globulin), markers of dyslipidemia (high-density lipoprotein cholesterol and triglycerides), inflammation [C-reactive protein (CRP)], an adipokine (adiponectin), and metabolites, stratified by sex. Results: Coffee consumption was inversely associated with diacylphosphatidylcholine C32:1 in both sexes and with phenylalanine in men, as well as positively associated with acyl-alkyl-phosphatidylcholines C34:3, C40:6, and C42:5 in women. Furthermore, coffee consumption was inversely associated with fetuin-A (P-trend = 0.06) and CRP in women and g-glutamyltransferase and triglycerides in men. Coffee consumption tended to be inversely associated with T2D risk in both sexes, reaching significance only in men [HR (95% CI): women: 4comparedwith.0to,2cupscoffee/d:0.78(0.46,1.33);men:4 compared with .0 to ,2 cups coffee/d: 0.78 (0.46, 1.33); men: 4comparedwith.0to,2cupscoffee/d:0.78(0.46,1.33);men:5 compared with .0 to ,2 cups coffee/d: 0.40 (0.19, 0.81)]. The association between coffee consumption and T2D risk in men was slightly reduced after adjustment for phenylalanine or lipid markers. Conclusions: Coffee consumption was inversely associated with a diacyl-phosphatidylcholine and liver markers in both sexes and positively associated with certain acyl-alkyl-phosphatidylcholines in women. Furthermore, coffee consumption showed an inverse trend with CRP in women and with triglycerides and phenylalanine in men. However, these markers explained only to a small extent the inverse association between long-term coffee consumption and T2D risk.

BMJ (Clinical research ed.), Jan 10, 2014

To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to inv... more To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. Mendelian randomisation meta-analysis of 56 epidemiological studies. 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5....

British Journal of Nutrition, 2004

Folate deficiency is often discussed as a potential risk factor for CVD and some cancers. Reliabl... more Folate deficiency is often discussed as a potential risk factor for CVD and some cancers. Reliable assessment of folate status in large-scale epidemiological studies is therefore of major importance. The present study assessed the value of plasma folate (PF) compared with erythrocyte folate (EF) as a marker of folate status in 363 participants in the European Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. EF and PF, total homocysteine (tHcy), pyridoxine, cobalamin, creatinine, total protein and packed cell volume were determined; glutamate carboxypeptidase (GCP) C1561T, reduced folate carrier (RFC) G80A and methylenetetrahydrofolate (MTHFR) C677T polymorphisms were analysed. Anthropometric measurements were taken and dietary intake was assessed with the EPIC-Potsdam food-frequency questionnaire. Comparison of EF and PF with factors that may modulate their concentrations was performed. Cross-classification of blood folates in quintile categories resulted in correct cl...

PLoS ONE, 2011

Metabolomics is a promising tool for discovery of novel biomarkers of chronic disease risk in pro... more Metabolomics is a promising tool for discovery of novel biomarkers of chronic disease risk in prospective epidemiologic studies. We investigated the between-and within-person variation of the concentrations of 163 serum metabolites over a period of 4 months to evaluate the metabolite reliability expressed by the intraclass-correlation coefficient (ICC: the ratio of between-person variance and total variance). The analyses were performed with the BIOCRATES AbsoluteIDQ TM targeted metabolomics technology, including acylcarnitines, amino acids, glycerophospholipids, sphingolipids and hexose in 100 healthy individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study who had provided two fasting blood samples 4 months apart. Overall, serum reliability of metabolites over a 4-month period was good. The median ICC of the 163 metabolites was 0.57. The highest ICC was observed for hydroxysphingomyelin C14:1 (ICC = 0.85) and the lowest was found for acylcarnitine C3:1 (ICC = 0). Reliability was high for hexose (ICC = 0.76), sphingolipids (median ICC = 0.66; range: 0.24-0.85), amino acids (median ICC = 0.58; range: 0.41-0.72) and glycerophospholipids (median ICC = 0.58; range: 0.03-0.81). Among acylcarnitines, reliability of short and medium chain saturated compounds was good to excellent (ICC range: 0.50-0.81). Serum reliability was lower for most hydroxyacylcarnitines and monounsaturated acylcarnitines (ICC range: 0.11-0.45 and 0.00-0.63, respectively). For most of the metabolites a single measurement may be sufficient for risk assessment in epidemiologic studies with healthy subjects.

PLoS ONE, 2013

Objective: Obesity has become a leading preventable cause of morbidity and mortality in many part... more Objective: Obesity has become a leading preventable cause of morbidity and mortality in many parts of the world. It is thought to originate from multiple genetic and environmental determinants. The aim of the current study was to introduce haplotype-based multi-locus stepwise regression (MSR) as a method to investigate combinations of unlinked single nucleotide polymorphisms (SNPs) for obesity phenotypes. Methods: In 2,122 healthy randomly selected men and women of the EPIC-Potsdam cohort, the association between 41 SNPs from 18 obesity-candidate genes and either body mass index (BMI, mean = 25.9 kg/m 2 , SD = 4.1) or waist circumference (WC, mean = 85.2 cm, SD = 12.6) was assessed. Single SNP analyses were done by using linear regression adjusted for age, sex, and other covariates. Subsequently, MSR was applied to search for the 'best' SNP combinations. Combinations were selected according to specific AIC c and p-value criteria. Model uncertainty was accounted for by a permutation test. Results: The strongest single SNP effects on BMI were found for TBC1D1 rs637797 (b = 20.33, SE = 0.13), FTO rs9939609 (b = 0.28, SE = 0.13), MC4R rs17700144 (b = 0.41, SE = 0.15), and MC4R rs10871777 (b = 0.34, SE = 0.14). All these SNPs showed similar effects on waist circumference. The two 'best' six-SNP combinations for BMI (global p-value = 3.45?10-6 and 6.82?10-6) showed effects ranging from 21.70 (SE = 0.34) to 0.74 kg/m 2 (SE = 0.21) per allele combination. We selected two six-SNP combinations on waist circumference (global p-value = 7.80?10-6 and 9.76?10-6) with an allele combination effect of 22.96 cm (SE = 0.76) at maximum. Additional adjustment for BMI revealed 15 three-SNP combinations (global p-values ranged from 3.09?10-4 to 1.02?10-2). However, after carrying out the permutation test all SNP combinations lost significance indicating that the statistical associations might have occurred by chance. Conclusion: MSR provides a tool to search for risk-related SNP combinations of common traits or diseases. However, the search process does not always find meaningful SNP combinations in a dataset.

European Journal of Clinical Nutrition, 2013

BACKGROUND/OBJECTIVE: Serum metabolites have been linked to higher risk of chronic diseases but d... more 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.

American Journal of Epidemiology, 2007