Susanne Vogt

Multi-omic signature of body weight change: results from a population-based cohort study

BackgroundExcess body weight is a major risk factor for cardiometabolic diseases. The complex molecular mechanisms of body weight change-induced metabolic perturbations are not fully understood. Specifically, in-depth molecular characterization of long-term body weight change in the general population is lacking. Here, we pursued a multi-omic approach to comprehensively study metabolic consequences of body weight change during a seven-year follow-up in a large prospective study.MethodsWe used data from the population-based Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 cohort. At follow-up (F4), two-platform serum metabolomics and whole blood gene expression measurements were obtained for 1,631 and 689 participants, respectively. Using weighted correlation network analysis, omics data were clustered into modules of closely connected molecules, followed by the formation of a partial correlation network from the modules. Association of the omics modules with previous annual percentage weight change was then determined using linear models. In addition, we performed pathway enrichment analyses, stability analyses, and assessed the relation of the omics modules with clinical traits.ResultsFour metabolite and two gene expression modules were significantly and stably associated with body weight change (P-values ranging from 1.9 × 10−4 to 1.2 × 10−24). The four metabolite modules covered major branches of metabolism, with VLDL, LDL and large HDL subclasses, triglycerides, branched-chain amino acids and markers of energy metabolism among the main representative molecules. One gene expression module suggests a role of weight change in red blood cell development. The other gene expression module largely overlaps with the lipid-leukocyte (LL) module previously reported to interact with serum metabolites, for which we identify additional co-expressed genes. The omics modules were interrelated and showed cross-sectional associations with clinical traits. Moreover, weight gain and weight loss showed largely opposing associations with the omics modules.ConclusionsLong-term weight change in the general population globally associates with serum metabolite concentrations. An integrated metabolomics and transcriptomics approach improved the understanding of molecular mechanisms underlying the association of weight gain with changes in lipid and amino acid metabolism, insulin sensitivity, mitochondrial function as well as blood cell development and function.

Prospective association of vitamin D with frailty status and all-cause mortality in older adults: Results from the KORA-Age Study.

OBJECTIVE To assess the prospective association of serum 25-hydroxyvitamin D [25(OH)D] levels with frailty status and all-cause mortality in a cohort of community-dwelling participants of the population-based KORA [Cooperative Health Research in the Region of Augsburg]-Age Study. METHODS 727 non-frail participants, aged ≥65years, with 25(OH)D measurement at baseline in 2009, were followed for 2.9±0.1years. Participants were classified as pre-frail or frail if they met 1-2 or ≥3, respectively, of the following five criteria: weight loss, exhaustion, physical inactivity, low walking speed, weakness. The association between 25(OH)D and mortality was assessed in 954 participants. Multivariable adjusted logistic regression models were calculated for each outcome. RESULTS The incidence of pre-frailty and frailty was 21.2% and 3.9% respectively. After multivariable adjustment, participants with very low 25(OH)D levels (<15ng/ml vs. ≥30ng/ml) had a significantly higher odds for pre-frailty (OR=2.43 [95% CI: 1.17-5.03]) and pre-frailty/frailty combined (OR=2.53 [95% CI: 1.23-5.22]), but not for frailty alone (OR=2.63 [95% CI: 0.39-17.67]). The association between 25(OH)D and mortality (OR=3.39 [95% CI: 1.08-10.65]) was partly mediated by frailty status. CONCLUSION Very low 25(OH)D levels were independently associated with incident pre-frailty, pre-frailty/frailty combined and all-cause mortality.

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.

Comparison of different measures of obesity in their association with health-related quality of life in older adults – results from the KORA-Age study

OBJECTIVE As ageing is associated with changes in body composition, BMI may not be the appropriate obesity measure for older adults. To date, little is known about associations between obesity measures and health-related quality of life (HRQoL). Thus, we aimed to compare different obesity measures in their association with HRQoL and self-rated physical constitution (SRPC) in older adults. DESIGN Seven obesity measures (BMI, waist circumference (WC), waist-to-hip ratio, waist-to-height ratio, fat mass percentage based on bioelectrical impedance analysis, hypertriglyceridaemic waist (HTGW) and sarcopenic obesity) were assessed at baseline in 2009. HRQoL, using the EQ-5D questionnaire, and SRPC, using one single question, were collected at baseline and at the 3-year follow-up in 2012. Linear and logistic regression analyses were used to examine the associations between the obesity measures and both outcomes. Model comparisons were conducted by area under the receiver-operating characteristic curve, R 2, Akaike and Schwarz Bayesian information criteria. SETTING KORA-Age study in Southern Germany (2009-2012). SUBJECTS Older adults (n 883; aged ≥65 years). RESULTS Nearly all obesity measures were significantly inversely associated with both outcomes in cross-sectional analyses. Concerning HRQoL, the WC model explained most of the variance and had the best model adaption, followed by the BMI model. Regarding SRPC, the HTGW and BMI models were best as rated by model quality criteria, followed closely by the WC model. Longitudinal analyses showed no significant associations. CONCLUSIONS These results suggest that, with regard to HRQoL/SRPC, simple anthropometric measures are sufficient to determine obesity in older adults in medical practice.

Effect of waist circumference on the association between serum 25-hydroxyvitamin D and serum lipids: results from the National Health and Nutrition Examination Survey 2001-2006.

OBJECTIVE To examine the interaction between waist circumference (WC) and serum 25-hydroxyvitamin D (25(OH)D) level in their associations with serum lipids. DESIGN Cross-sectional study. The associations of serum 25(OH)D with total cholesterol, HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), LDL-C:HDL-C and TAG were examined using multiple linear regression. Effect modification by WC was assessed through cross-product interaction terms between 25(OH)D and WC categories (abdominal overweight, 80-<88 cm in females/94-<102 cm in males; abdominal obesity, ≥88 cm in females/≥102 cm in males). SETTING The US National Health and Nutrition Examination Survey waves 2001-2006. SUBJECTS Non-pregnant fasting participants (n 4342) aged ≥20 years. RESULTS Lower 25(OH)D levels were significantly associated with lower HDL-C levels as well as with higher LDL-C:HDL-C and TAG levels in abdominally obese participants, but not in abdominally overweight or normal-waist participants. In contrast, lower 25(OH)D levels were associated with lower levels of total cholesterol and LDL-C in abdominally overweight and normal-waist participants only, but this association was only partly significant. However, a significant difference in the association between 25(OH)D and the lipids according to WC category was found only for LDL-C:HDL-C (P for interaction=0·02). CONCLUSIONS Our results from this large, cross-sectional sample suggest that the association between lower 25(OH)D levels and an unfavourable lipid profile is stronger in individuals with abdominal obesity than in those with abdominal overweight or a normal WC.

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.

Waist circumference modifies the association between serum 25(OH)D and systolic blood pressure: results from NHANES 2001-2006.

Objective: Results on the association between vitamin D and blood pressure are conflicting and little is known about how their relationship may be affected by obesity. Thus, we explored whether waist circumference modified the association between serum 25-hydroxyvitamin D (25(OH)D) and blood pressure in participants of the U.S. National Health and Nutrition Examination Surveys 2001–2006. Methods: We included 10 331 nonpregnant participants aged 20 years or older. The association of serum 25(OH)D with systolic and diastolic blood pressure, in the total sample and stratified by waist circumference category (abdominal overweight: 80 to <88 cm in females / 94 to <102 cm in males; abdominal obesity: ≥88 cm in females/ ≥102 cm in males), was examined using multiple linear regression. Effect modification by waist circumference was assessed through a cross-product interaction term between 25(OH)D category and waist circumference category. Results: Waist circumference significantly modified the inverse association between 25(OH)D and systolic blood pressure (SBP) (P value for interaction: 0.09). A stronger association of 25(OH)D levels below 15 ng/ml (reference: ≥30 ng/ml) with SBP was found in abdominally obese (&bgr; = 3.5 mmHg) than in abdominally overweight (&bgr; = 2.0 mmHg) and normal waist participants (&bgr; = 1.2 mmHg), but this interaction was only significant in participants without antihypertensive treatment. No significant effect modification was found for diastolic blood pressure. Conclusion: Results from this large, cross-sectional sample suggest that the association between 25(OH)D and SBP is stronger in individuals with abdominal obesity than in those with a normal waist or with abdominal overweight.

Association of serum vitamin D with change in weight and total body fat in a German cohort of older adults

We examined the association of baseline serum 25-hydroxyvitamin D (25(OH)D) with change in weight and total body fat in a cohort of community-dwelling older adults from Southern Germany. A total of 735 participants of the population-based KORA-Age Study (2009–2012), aged 65–90 years, were followed for 2.9±0.1 years. Body fat was assessed with bioelectrical impedance analysis. Linear and multinomial logistic models, adjusted for baseline covariables, were used to examine the association of 25(OH)D with percentage weight and body fat change during follow-up. 25(OH)D levels were not associated with overall weight change or body fat loss. Higher 25(OH)D levels were associated with a lower likelihood of having gained >3% of body fat in women but not in men. As we cannot exclude residual confounding by outdoor physical activity and diet, our results are not sufficient to support a causal role of 25(OH)D in the etiology of obesity in Caucasian older adults.

Predicting risk of substantial weight gain in German adults—a multi-center cohort approach

Abstract Background A risk-targeted prevention strategy may efficiently utilize limited resources available for prevention of overweight and obesity. Likewise, more efficient intervention trials could be designed if selection of subjects was based on risk. The aim of the study was to develop a risk score predicting substantial weight gain among German adults. Methods We developed the risk score using information on 15 socio-demographic, dietary and lifestyle factors from 32 204 participants of five population-based German cohort studies. Substantial weight gain was defined as gaining ≥10% of weight between baseline and follow-up (>6 years apart). The cases were censored according to the theoretical point in time when the threshold of 10% baseline-based weight gain was crossed assuming linearity of weight gain. Beta coefficients derived from proportional hazards regression were used as weights to compute the risk score as a linear combination of the predictors. Cross-validation was used to evaluate the score’s discriminatory accuracy. Results The cross-validated c index (95% CI) was 0.71 (0.67–0.75). A cutoff value of ≥475 score points yielded a sensitivity of 71% and a specificity of 63%. The corresponding positive and negative predictive values were 10.4% and 97.6%, respectively. Conclusions The proposed risk score may support healthcare providers in decision making and referral and facilitate an efficient selection of subjects into intervention trials.