Benedikt Merz

Metabolite patterns predicting sex and age in participants of the Karlsruhe Metabolomics and Nutrition (KarMeN) study

Physiological and functional parameters, such as body composition, or physical fitness are known to differ between men and women and to change with age. The goal of this study was to investigate how sex and age-related physiological conditions are reflected in the metabolome of healthy humans and whether sex and age can be predicted based on the plasma and urine metabolite profiles. In the cross-sectional KarMeN (Karlsruhe Metabolomics and Nutrition) study 301 healthy men and women aged 18–80 years were recruited. Participants were characterized in detail applying standard operating procedures for all measurements including anthropometric, clinical, and functional parameters. Fasting blood and 24 h urine samples were analyzed by targeted and untargeted metabolomics approaches, namely by mass spectrometry coupled to one- or comprehensive two-dimensional gas chromatography or liquid chromatography, and by nuclear magnetic resonance spectroscopy. This yielded in total more than 400 analytes in plasma and over 500 analytes in urine. Predictive modelling was applied on the metabolomics data set using different machine learning algorithms. Based on metabolite profiles from urine and plasma, it was possible to identify metabolite patterns which classify participants according to sex with > 90% accuracy. Plasma metabolites important for the correct classification included creatinine, branched-chain amino acids, and sarcosine. Prediction of age was also possible based on metabolite profiles for men and women, separately. Several metabolites important for this prediction could be identified including choline in plasma and sedoheptulose in urine. For women, classification according to their menopausal status was possible from metabolome data with > 80% accuracy. The metabolite profile of human urine and plasma allows the prediction of sex and age with high accuracy, which means that sex and age are associated with a discriminatory metabolite signature in healthy humans and therefore should always be considered in metabolomics studies.

Changes in body weight and obesity status in German adults: results of seven population-based prospective studies

Background/Objectives:The objective of this study was to quantify body weight changes in German adult populations during the past decades.Subjects/Methods:Longitudinal analysis of seven cohort studies covering different age ranges between 18 and 83 years. Baseline examinations were between 1994 and 2007 and follow-up durations between 4.0 and 11.9 years. For each study, mean change in body weight per year and 10-year change in body mass index (BMI) classification were analyzed. For the middle age group of 45–64 years, meta-analysis was conducted to obtain an overall estimate for Germany.Results:Among men weight gain was highest in the youngest participants and decreased with advancing age. Among women weight gain was on a stable high level among those younger than 45 years and decreased at older age. Within 10 years, 30–40% of middle-aged participants with normal baseline weight became pre-obese or obese and 20–25% of those with pre-obesity at baseline became obese, whereas >80% of persons who were obese at baseline remained obese over time. The estimated average weight change in adults aged 45–64 years was 0.25 (95% confidence interval (CI): 0.18–0.33) kg/year among men and 0.24 (0.17–0.30) kg/year among women.Conclusions:We could observe a moderate weight gain over the past years in German middle-aged populations of 0.25 kg/year. Obesity prevention needs to be targeted to specific subgroups in the population, especially to younger adults, who seem to be most vulnerable for gaining weight. Obesity intervention needs to be improved, as the majority of obese adults remained obese over time.

Socioeconomic status and anthropometric changes-A meta-analytic approach from seven German cohorts.

To study the association between socioeconomic status (SES) and annual relative change in anthropometric markers in the general German adult population.

Changes in Waist Circumference among German Adults over Time - Compiling Results of Seven Prospective Cohort Studies

Aim: This study aims to quantify longitudinal changes in waist circumference (WC) among adults aged 45-64 years in Germany. Methods: Data of 15,444 men and 17,207 women from one nationwide and six regional prospective German cohort studies were analyzed. The sex-specific mean change in WC per year of follow-up was assessed for each study separately. Findings from the cohort-by-cohort analysis were combined by applying meta-analytic methods. Progression to central obesity (WC ≥ 102 cm in men and ≥ 88 cm in women) within a standardized period of 10 years was described for each study. Results: The estimated mean change in WC per year of follow-up for all cohorts combined was 0.53 (95% confidence interval 0.29-0.76) cm/year for men and 0.63 (0.48-0.77) cm/year for women, but varied between the included studies. Within 10 years, about 20% of individuals with low WC (<94 cm in men; <80 cm in women) and about 50% of individuals with intermediate WC (94-102 cm in men; 80-88 cm in women) progressed to central obesity. Conclusion: The increase in mean WC with aging along with a profound increase of central adiposity is obviously and may have several adverse health effects. Obesity prevention programs should also focus on abdominal obesity.

Dietary Pattern and Plasma BCAA-Variations in Healthy Men and Women—Results from the KarMeN Study

Branched-chain amino acids (BCAA) in plasma are discussed as risk factors for the onset of several diseases. Information about the contribution of the overall diet to plasma BCAA concentrations is controversial. Our objective was to investigate which dietary pattern is associated with plasma BCAA concentrations and whether other additional nutrients besides BCAA further characterize this dietary pattern. Based on the cross-sectional KarMeN study, fasting plasma amino acid (AA) concentrations, as well as current and habitual dietary intake were assessed in 298 healthy individuals. Using reduced rank regression, we derived a habitual dietary pattern that explained 32.5% of plasma BCAA variation. This pattern was high in meat, sausages, sauces, eggs, and ice cream but low in nuts, cereals, mushrooms, and pulses. The age, sex, and energy intake adjusted dietary pattern score was associated with an increase in animal-based protein together with a decrease in plant-based protein, dietary fiber, and an unfavorable fatty acid composition. Besides BCAA, alanine, lysine and the aromatic AA were positively associated with the dietary pattern score as well. All of these factors were reported to be associated with risk of type 2 diabetes and cardiovascular diseases before. Our data suggest that rather than the dietary intake of BCAA, the overall dietary pattern that contributes to high BCAA plasma concentrations may modulate chronic diseases risk.

Specific Metabolic Markers Are Associated with Future Waist-Gaining Phenotype in Women.

Objective Our study aims to identify metabolic markers associated with either a gain in abdominal (measured by waist circumference) or peripheral (measured by hip circumference) body fat mass. Methods Data of 4 126 weight-gaining adults (18–75 years) from three population-based, prospective German cohort studies (EPIC, KORA, DEGS) were analysed regarding a waist-gaining (WG) or hip-gaining phenotype (HG). The phenotypes were obtained by calculating the differences of annual changes in waist minus hip circumference. The difference was displayed for all cohorts. The highest 10% of this difference were defined as WG whereas the lowest 10% were defined as HG. A total of 121 concordant metabolite measurements were conducted using Biocrates AbsoluteIDQ® kits in EPIC and KORA. Sex-specific associations with metabolite concentration as independent and phenotype as the dependent variable adjusted for confounders were calculated. The Benjamini-Hochberg method was used to correct for multiple testing. Results Across studies both sexes gained on average more waist than hip circumference. We could identify 12 metabolites as being associated with the WG (n = 8) or HG (n = 4) in men, but none were significant after correction for multiple testing; 45 metabolites were associated with the WG (n = 41) or HG (n = 4) in women. For WG, n = 21 metabolites remained significant after correction for multiple testing. Respective odds ratios (OR) ranged from 0.66 to 0.73 for tryptophan, the diacyl-phosphatidylcholines (PC) C32:3, C36:0, C38:0, C38:1, C42:2, C42:5, the acyl-alkyl-PCs C32:2, C34:0, C36:0, C36:1, C36:2, C38:0, C38:2, C40:1, C40:2, C40:5, C40:6, 42:2, C42:3 and lyso-PC C17:0. Conclusion Both weight-gaining men and women showed a clear tendency to gain more abdominal than peripheral fat. Gain of abdominal fat seems to be related to an initial metabolic state reflected by low concentrations of specific metabolites, at least in women. Thus, higher levels of specific PCs may play a protective role in gaining waist circumference.

Dataset from Merz B, Frommherz L, Rist MJ, Kulling SE, Bub A, Watzl B. "Dietary Pattern and Plasma BCAA-Variations in Healthy Men and Women – Results from the KarMeN Study"

This dataset contains the underlying research data for the paper: Merz, B.; Frommherz, L.; Rist, M.J.; Kulling, S.E.; Bub, A.; Watzl, B. Dietary Pattern and Plasma BCAA-Variations in Healthy Men and Women—Results from the KarMeN Study. Nutrients 2018, 10, 623. The tab-delimeted data file contains information of participants from the Karlsruhe Metabolomics and Nutrition (KarMeN) Study including descriptive metadata, plasma amino acid concentrations assessed via liquid chromatography–mass spectrometry, information on current dietary intake (food group level) assessed via 24h recall and information on habitual dietary intake (food group level and selected macronutrients) calculated with the NCI method. The dataset also includes an annotation file that is providing additional information such as unit, decoding of used abbreviations and a description of the included food groups.

Changes in fat mass and fat-free-mass are associated with incident hypertension in four population-based studies from Germany

BACKGROUND We estimated the association of changes in body weight, waist circumference (WC), fat mass (FM) and fat-free mass (FFM) with changes in blood pressure and incident hypertension using data from four German population-based studies. METHODS We analyzed data from 4467 participants, aged 21 to 82 years not taking antihypertensive medication and not having type 2 diabetes mellitus or a history of myocardial infarction at baseline and follow-up, from four population-based studies conducted in Germany. Body weight, WC, and blood pressure were measured at baseline and follow-up (median follow-up of the single studies 4 to 7 years). FM and FFM were calculated based on height-weight models derived from bioelectrical impedance studies. Hypertension was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg. Confounder-adjusted linear and logistic regressions were used to associate changes in anthropometric markers with changes in blood pressure, incident hypertension, and incident normalization of blood pressure. RESULTS In a pooled dataset including all four studies, increments in body weight, WC, FM, and FFM were statistically significantly associated with incident hypertension and changes in systolic and diastolic blood pressure over time. Decreases in body weight, FM, and FFM were significantly associated with incident normalization of blood pressure. CONCLUSIONS Our data suggests that the well-established association between obesity and blood pressure levels might be more related to body composition rather than to total body weight per se. Our findings indicate that gaining or losing FFM has substantial impact on the development or reversion of hypertension.