Social factors and the prevalence of social isolation in a population-based adult cohort.

PURPOSE: Social isolation has negative effects on physical and brain health across the lifespan. However, the prevalence of social isolation, specifically with regard to sociodemographic and socioeconomic factors, is not well known. METHODS: Database was the Leipzig population-based study of adults (LIFE-Adult Study, n = 10,000). The short form of the Lubben Social Network Scale (LSNS-6) was used to assess social isolation (cutoff < 12 points). Sampling weights were applied to account for differences in sampling fractions. RESULTS: Data were available for 9392 study participants; 51.6% were women, the mean age was 45.2 years (SD = 17.3). The prevalence of social isolation was 12.3% (95% CI 11.6-13.0) across ages 18-79 years. Social isolation was more prevalent in men (13.8%, 95% CI 12.8-14.8) compared to women (10.9%, 95% CI 10.0-11.8; [Formula: see text] (1) = 18.83, p < .001), and it showed an increase with increasing age from 5.4% (95% CI 4.7-6.0) in the youngest age group (18-39 years) to 21.7% (95% CI 19.5-24.0) in the oldest age group (70-79 years; [Formula: see text] (4) = 389.51, p < .001). Prevalence differed largely with regard to socioeconomic status (SES); showing lower prevalence in high SES (7.2%, 95% CI 6.0-8.4) and higher prevalence in low SES (18.6%, 95% CI 16.9-20.3; [Formula: see text] (2) = 115.78; p < .001). CONCLUSION: More than one in ten individuals in the adult population reported social isolation, and prevalence varied strongly with regard to sociodemographic and socioeconomic factors. Social isolation was particularly frequent in disadvantaged socioeconomic groups. From a public health perspective, effective prevention of and intervention against social isolation should be a desired target as social isolation leads to poor health. Countermeasures should especially take into account the socioeconomic determinants of social isolation, applying a life-course perspective.

Facilitating harmonized data quality assessments. A data quality framework for observational health research data collections with software implementations in R.

BACKGROUND: No standards exist for the handling and reporting of data quality in health research. This work introduces a data quality framework for observational health research data collections with supporting software implementations to facilitate harmonized data quality assessments. METHODS: Developments were guided by the evaluation of an existing data quality framework and literature reviews. Functions for the computation of data quality indicators were written in R. The concept and implementations are illustrated based on data from the population-based Study of Health in Pomerania (SHIP). RESULTS: The data quality framework comprises 34 data quality indicators. These target four aspects of data quality: compliance with pre-specified structural and technical requirements (integrity); presence of data values (completeness); inadmissible or uncertain data values and contradictions (consistency); unexpected distributions and associations (accuracy). R functions calculate data quality metrics based on the provided study data and metadata and R Markdown reports are generated. Guidance on the concept and tools is available through a dedicated website. CONCLUSIONS: The presented data quality framework is the first of its kind for observational health research data collections that links a formal concept to implementations in R. The framework and tools facilitate harmonized data quality assessments in pursue of transparent and reproducible research. Application scenarios comprise data quality monitoring while a study is carried out as well as performing an initial data analysis before starting substantive scientific analyses but the developments are also of relevance beyond research.

Income in relation to obesity measures in an East German adult population: findings from the LIFE-Adult-Study.

BACKGROUND: Obesity has been postulated to be a consequence of economic disadvantage. However, epidemiological studies failed to demonstrate a consistent link between income and body fat indicators. We examined income as a possible cause of obesity in an East German general population, focusing on appropriate representation of study variables, as well as on confounding and modification of the income-obesity association. METHODS: We used data of 9599 participants in the baseline examination of the LIFE-Adult-Study, conducted in the city of Leipzig from 2011 to 2014. Body mass index (BMI) and waist circumference (WC) as obesity measures were based on standardised measurements, net equivalised income (NEI) on self-reports. We estimated adjusted means of BMI and WC within NEI categories representing the range from risk of poverty to affluence. We stratified the analyses by gender, age, and education. RESULTS: A substantial part of the age-adjusted associations of income with obesity measures was attributable to other SES indicators. Adjusted for these variables, NEI was comparably associated with BMI and WC. Among women, BMI and WC decreased across NEI categories. The inverse associations tended to be stronger at non-working age (≥ 65 years) than at working age (< 65 years). Conversely, among working-age men, BMI and WC increased with increasing NEI. Among older men, risk of poverty was related to higher values of the obesity measures. The aforementioned associations were predominantly stronger in highly educated participants compared to those with medium/low education. The differences in mean BMI and WC between persons at risk of poverty and higher income groups were rather small, ranging from 1 to 2 kg/m2 for BMI and 2 to 4 cm for WC. CONCLUSIONS: Our investigation indicates an association between income and body fatness in an East German adult population that depends on the sociodemographic context of the people. However, it does not suggest that income disparities are a major driver of body fat accumulation in this population. Differential selection of study participants, error in the measurement of long-term income, and possibly reverse causality may have affected our conclusions.

Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood.

Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG consortium), as well as that with blood pressure using publicly available summary-level genome-wide association data from EGG consortium of 153,781 participants, ICBP consortium and UK Biobank cohort together of 757,601 participants. We used seven SNPs as the instrumental variable in the study-level analysis and 47 SNPs in the summary-level analysis. In the study-level analyses, decreased birthweight was associated with a higher risk of hypertension in adults (the odds ratio per 1 standard deviation (SD) lower birthweight, 1.22; 95% CI 1.16 to 1.28), while no association was found between genetically instrumented birthweight and hypertension risk (instrumental odds ratio for causal effect per 1 SD lower birthweight, 0.97; 95% CI 0.68 to 1.41). Such results were consistent with that from the summary-level analyses, where the genetically determined low birthweight was not associated with blood pressure measurements either. One SD lower genetically determined birthweight was not associated with systolic blood pressure (ß = - 0.76, 95% CI - 2.45 to 1.08 mmHg), 0.06 mmHg lower diastolic blood pressure (ß = - 0.06, 95% CI - 0.93 to 0.87 mmHg), or pulse pressure (ß = - 0.65, 95% CI - 1.38 to 0.69 mmHg, all p > 0.05). Our findings suggest that the inverse association of birthweight with hypertension risk from observational studies was not supported by large Mendelian randomization analyses.

The association between mental demands at the workplace and cognitive functioning: the role of the big five personality traits.

Objectives: Mental demands at the workplace can be preventive against cognitive decline. However, personality shapes the way information is processed and we therefore assume that Neuroticism, Extraversion, Openness, Agreeableness and Conscientiousness, would moderate the beneficial effects of workplace stimulation on cognitive outcomes.Methods: We analyzed data from the population-based LIFE-Adult-Study (n = 6529). Cognitive outcomes were assessed via the Trail-Making Test (TMTA, TMTB) and the Verbal Fluency Test. Personality was assessed via the Personality Adjective List (16 AM). Mental demands were classified with the indices Verbal and Executive based on the O*NET database.Results: Multivariate regression analyses showed only two significant moderation effects of personality, i.e. in individuals with low scores on Conscientiousness/Openness, index Verbal was connected to better TMTB performance, while this effect disappeared for individuals with high values on the personality trait. However, the additional explained variance remained marginal.Conclusion: The findings suggest that personality does not modify associations between high mental demands at work and better cognitive functioning in old age; however, there is a tendency that high levels of Openness and Conscientiousness may offset effects of mental demands.

Evaluating selection bias in a population-based cohort study with low baseline participation: the LIFE-Adult-Study.

BACKGROUND: Participation in epidemiologic studies is steadily declining, which may result in selection bias. It is therefore an ongoing challenge to clarify the determinants of participation to judge possible selection effects and to derive measures to minimise that bias. We evaluated the potential for selection bias in a recent population-based cohort study with low baseline participation and investigated reasons for nonparticipation. METHODS: LIFE-Adult is a cohort study in the general population of the city of Leipzig (Germany) designed to gain insights into the distribution and development of civilisation diseases. Nine thousand one hundred forty-five participants aged 40-79 years were randomly sampled in 2011-2014. We compared LIFE-Adult participants with both the Leipzig population and nonparticipants using official statistics and short questionnaire data. We applied descriptive statistics and logistic regression analysis to evaluate the determinants of study participation. RESULTS: Thirty-one percent of the invited persons participated in the LIFE-Adult baseline examination. Study participants were less often elderly women and more often married, highly educated, employed, and current nonsmokers compared to both the Leipzig population and nonparticipants. They further reported better health than nonparticipants. The observed differences were considerable in education and health variables. They were generally stronger in men than in women. For example, in male study participants aged 50-69, the frequency of high education was 1.5 times that of the general population, and the frequency of myocardial infarction was half that of nonparticipants. Lack of time and interest, as well as health problems were the main reasons for nonparticipation. CONCLUSIONS: Our investigation suggests that the low baseline participation in LIFE-Adult is associated with the typical selection of study participants with higher social status and healthier lifestyle, and additionally less disease. Notably, education and health status seem to be crucial selection factors. Consequently, frequencies of major health conditions in the general population will likely be underestimated. A differential selection related to sex might also distort effect estimates. The extent of the assessment, the interest in the research topic, and health problems of potential participants should in future be considered in LIFE-Adult and in similar studies to raise participation and to minimise selection bias.

[Quality standards for epidemiologic cohort studies : An evaluated catalogue of requirements for the conduct and preparation of cohort studies]. / Qualitätsstandards für epidemiologische Kohortenstudien : Ein bewerteter Anforderungskatalog zur Studienvorbereitung und Studiendurchführung.

BACKGROUND: Cohort studies are a longitudinal observational study type. They are firmly established within epidemiology to assess the course of diseases and risk factors. Yet, standards to describe and evaluate quality characteristics of cohort studies need further development. OBJECTIVE: Within the TMF ("Technologie- und Methodenplattform für die vernetzte medizinische Forschung e. V.") project "Quality management standards in cohort studies", a catalogue of requirements was compiled and evaluated, focusing on the preparation and conduct of epidemiologic cohort studies. MATERIALS AND METHODS: The catalogue of requirements was established based on a consensus process between representatives of seven German epidemiologic cohort studies. For this purpose, a set of expert meetings (telephone, face-to-face, web-based) was conducted and the importance of each element of the catalogue was assessed as well as its implementation. RESULTS: A catalogue of requirements with 138 requirements was consented. It is structured into ten sections: 1. Study documentation; 2. Selection of instruments; 3. Study implementation, 4. Organizational structure; 5. Qualification and certification; 6. Participant recruitment; 7. Preparation, conduct and follow-up processing of examinations; 8. Study logistics and maintenance, 9. Data capture and data management; 10. Reporting and monitoring. In total, 41 elements were categorized as being essential, 91 as important, and 6 as less important. CONCLUSION: The catalogue of requirements provides a guideline to improve the preparation and operation of cohort studies. The evaluation of the importance and degree of implementation of requirements depended on the study design. With adaptations, the catalogue might be transferable to other study types.

The LIFE-Adult-Study: objectives and design of a population-based cohort study with 10,000 deeply phenotyped adults in Germany.

BACKGROUND: The LIFE-Adult-Study is a population-based cohort study, which has recently completed the baseline examination of 10,000 randomly selected participants from Leipzig, a major city with 550,000 inhabitants in the east of Germany. It is the first study of this kind and size in an urban population in the eastern part of Germany. The study is conducted by the Leipzig Research Centre for Civilization Diseases (LIFE). Our objective is to investigate prevalences, early onset markers, genetic predispositions, and the role of lifestyle factors of major civilization diseases, with primary focus on metabolic and vascular diseases, heart function, cognitive impairment, brain function, depression, sleep disorders and vigilance dysregulation, retinal and optic nerve degeneration, and allergies. METHODS/DESIGN: The study covers a main age range from 40-79 years with particular deep phenotyping in elderly participants above the age of 60. The baseline examination was conducted from August 2011 to November 2014. All participants underwent an extensive core assessment programme (5-6 h) including structured interviews, questionnaires, physical examinations, and biospecimen collection. Participants over 60 underwent two additional assessment programmes (3-4 h each) on two separate visits including deeper cognitive testing, brain magnetic resonance imaging, diagnostic interviews for depression, and electroencephalography. DISCUSSION: The participation rate was 33 %. The assessment programme was accepted well and completely passed by almost all participants. Biomarker analyses have already been performed in all participants. Genotype, transcriptome and metabolome analyses have been conducted in subgroups. The first follow-up examination will commence in 2016.

Erythrocyte membrane phospholipid polyunsaturated fatty acids are related to plasma C-reactive protein and adiponectin in middle-aged German women and men.

PURPOSE: Modulation of circulating inflammatory markers and adiponectin may link PUFA to risk of diabetes and cardiovascular diseases. We investigated erythrocyte n-6 and n-3 PUFA in relation to plasma C-reactive protein (CRP) and adiponectin, and whether the Pro12Ala polymorphism in the PPARγ2 gene (PPARG2) modified these associations. METHODS: We conducted a cross-sectional analysis among 1,222 women and 758 men participating in the EPIC-Potsdam study. RESULTS: Most notably, in both sexes, higher linoleic acid (LA) was related to lower CRP (geometric mean outcome [mg/L], quintile 1, quintile 5, p for trend ≤ 0.01 unless otherwise stated: 0.95, 0.61 [women], 0.67, 0.51 [men]) and higher adiponectin (7.9, 9.1 [women], 5.3, 6.1 [men]), whereas higher γ-linolenic acid (GLA) and dihomo-γ-linolenic acid (DGLA) were related to higher CRP (GLA: 0.63, 0.92 [women], 0.55, 0.70, p = 0.08 [men], DGLA: 0.55, 1.07 [women], 0.52, 0.76 [men]) and lower adiponectin (GLA: 8.6, 8.0 [women], 5.8, 5.4, p = 0.08 [men], DGLA: 9.2, 7.9 [women], 5.9, 5.4, p = 0.08 [men]) adjusting for age and lifestyle. The associations mostly did neither strongly nor significantly vary by PPARG2 genotype. In women, Pro12Ala appeared to interact with arachidonic acid on CRP (p = 0.04), as well as with docosatetraenoic acid on CRP (p = 0.08) and adiponectin (p = 0.02). CONCLUSIONS: Our findings suggest that erythrocyte PUFA, particularly LA and n-6 higher unsaturated fatty acids, are related to circulating CRP and adiponectin. They do not indicate that PUFA strongly interact with the PPARG2 Pro12Ala variant on these risk markers.

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.

Determinants of Willingness to Pay for Health Insurance in Germany-Results of the Population-Based Health Study of the Leipzig Research Centre for Civilization Diseases (LIFE-Adult-Study).

Objective: To investigate which factors are associated with the willingness to pay (WTP) for health insurance. Methods: The analysis (n = 1,248 individuals) is based on data of a large population-based study-the Health Study of the Leipzig Research Centre for Civilization Diseases (LIFE-Adult-Study). With regard to WTP for health insurance, a contingent valuation method with a payment card was used. Several explanatory variables were included. For example, personality factors (in terms of agreeableness, conscientiousness, extraversion, neuroticism, and openness to experience) were assessed using the NEO-16 Adjective Measure. Results: Average WTP for health insurance per month equaled about €240 which corresponds to ~14% of household net equivalent income. Multiple regressions showed that an increased WTP was associated with lower age (ß = -1.7, p < 0.001), higher (log) household net equivalent income (ß = 153.6, p < 0.001), higher social support (ß = 2.0, p < 0.05), and private health insurance (ß = 131.1, p < 0.001). Furthermore, an increased WTP for health insurance was associated with higher openness to experience (ß = 10.1, p < 0.05), whereas it was not associated with agreeableness, conscientiousness, extraversion, and neuroticism. Conclusion: The quite large amount of average WTP for health insurance may suggest that individuals accept current contributions to health insurances and would probably accept higher contributions. While previous studies mainly focused on individuals in late life, we identified a link between socioeconomic, health-related factors, and personality factors (in terms of openness to experience) and WTP in the general adult population.

Less Animal-Based Food, Better Weight Status: Associations of the Restriction of Animal-Based Product Intake with Body-Mass-Index, Depressive Symptoms and Personality in the General Population.

Restricting animal-based products from diet may exert beneficial effects on weight status; however, less is known about such a diet and emotional health. Moreover, personality traits, for example high neuroticism, may contribute to restrictive eating habits and potentially confound diet-health associations. We aim to systematically assess if restrictive dietary intake of animal-based products relates to lower weight and higher depressive symptoms, and if differences in personality traits play a significant role. Cross-sectional data from the baseline LIFE-Adult study were collected from 2011-2014 in Leipzig, Germany (n = 8943). Main outcomes of interest were dietary frequency of animal-derived products in the last year measured using a Food Frequency Questionnaire (FFQ), body-mass-index (BMI) (kg/m2), and the Center of Epidemiological Studies Depression Scale (CES-D). Personality traits were assessed in a subsample of n = 7906 using the Five Factor Inventory (NEO-FFI). Higher restriction of animal-based product intake was associated with a lower BMI, but not with depression scores. Personality, i.e., lower extraversion, was related to lower frequency of animal product intake. Moreover, personality traits were significantly associated with depressive symptoms, i.e., higher neuroticism, lower extraversion, lower agreeableness, lower conscientiousness, and with higher BMI. These findings encourage future longitudinal studies to test the efficacy of restricting animal-based products as a preventive and therapeutic strategy for overweight and obesity.

Higher fasting ghrelin serum levels in active smokers than in former and never-smokers.

OBJECTIVES: Ghrelin, an orexigenic peptide hormone, promotes drug reward and is suspected to play a role in nicotine dependence. However, there is little data on whether ghrelin levels are associated with active and/or former smoking. The relationship between ghrelin serum levels and smoking status in a population-based sample of individuals was studied. METHODS: Total ghrelin was determined after an overnight fast in 1519 subjects participating in a population-based cohort study ('LIFE-Adult'). Tobacco consumption was assessed using both the questionnaire and interview. Generalised linear models with gamma distribution and log-link function were performed to analyse the association of total serum ghrelin with smoking status and the association between serum ghrelin and the amount of tobacco consumed in active smokers. RESULTS: Ghrelin levels were positively associated with active, but not former smoking (OR = 1.095; p = .002). This association was not moderated by sex (interaction of 'active smoking' and sex: p = .346). Ghrelin levels were not associated with the amount of tobacco consumed in active smokers. CONCLUSIONS: This study provides evidence that total ghrelin serum levels are positively associated with active smoking. No association was found for former smokers. A unique feature of the study is the large sample size.

Depressive Symptomatology in Early Retirees Associated With Reason for Retirement-Results From the Population-Based LIFE-Adult-Study.

BACKGROUND: Transition from employment to retirement is regarded a crucial event. However, there is mixed evidence on associations between retirement and mental health, especially regarding early retirement. In Germany, cases of early retirement due to ill health-particularly, mental ill health-are increasing. Therefore, we investigated the association between early retirement and depressive symptoms, including information on different types of early retirement. METHODS: We analyzed data from 4,808 participants of the population-based LIFE-Adult-Study (age: 40-65 years, 654 retired, 4,154 employed), controlling for sociodemographic information, social network, pre-existing health conditions, and duration of retirement. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Regression analysis using entropy balancing was applied to achieve covariate balance between retired and employed subjects. RESULTS: We found no overall-differences in depressive symptoms between employed and retired persons (men: b = -.52; p = 0.431; women: b = .05; p = .950). When looking at different types of early retirement, ill-health retirement was linked to increased depressive symptoms in women (b = 4.68, 95% CI = 1.71; 7.65), while voluntary retirement was associated with reduced depressive symptoms in men (b= -1.83, 95% CI = -3.22; -.43) even after controlling for covariates. For women, statutory retirement was linked to lower depressive symptomatology (b = -2.00, 95% CI = -3.99; -.02). CONCLUSION: Depressive symptomatology among early retirees depends on reason for retirement: For women, ill-health retirement is linked to higher levels of depressive symptoms. Women who retire early due to ill-health constitute a risk group for depressive symptoms that needs specific attention in the health care and social security system.

Are social conflicts at work associated with depressive symptomatology? Results from the population-based LIFE-Adult-Study.

BACKGROUND: Psychosocial stressors in the workplace can be detrimental to mental health. Conflicts at work, e.g. aggression, hostility or threats from coworkers, supervisors or customers, can be considered a psychosocial stressor, possibly increasing risk for depressive symptoms. Existing studies, however, differ in the assessment of social conflicts, i.e. as individual- or job-level characteristics. Here, we investigated the association between conflicts at work assessed as objective job characteristics, and depressive symptomatology, using data from a large population-based sample. Additionally, we investigated gender differences and the impact of personality traits and social resources. METHODS: We used data from the population-based LIFE-Adult-Study from Leipzig, Germany. Information on conflicts at work, assessed as job characteristics, were drawn from the Occupational Information Network, depressive symptoms were assessed via the Center for Epidemiological Studies Depression Scale. Multilevel linear regression models with individuals and occupations as levels of analysis were applied to investigate the association between conflicts at work and depressive symptoms. RESULTS: Our sample included 2164 employed adults (age: 18-65 years, mean: 49.3, SD: 7.9) in 65 occupations. No association between conflicts s at work and depressive symptomatology was found (men: b = - 0.14; p = 0.74, women: b = 0.17, p = 0.72). Risk for depression was mostly explained by individual-level factors like e.g. neuroticism or level of social resources. The model showed slightly higher explanatory power in the female subsample. CONCLUSION: Conflicts at work, assessed as objective job characteristics, were not associated with depressive symptoms. Possible links between interpersonal conflict and impaired mental health might rather be explained by subjective perceptions of social stressors and individual coping styles.

Pro-neurotensin depends on renal function and is related to all-cause mortality in chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) have a high risk of premature cardiovascular diseases (CVD) and show increased mortality. Pro-neurotensin (Pro-NT) was associated with metabolic diseases and predicted incident CVD and mortality. However, Pro-NT regulation in CKD and its potential role linking CKD and mortality have not been investigated, so far. METHODS: In a central lab, circulating Pro-NT was quantified in three independent cohorts comprising 4715 participants (cohort 1: patients with CKD; cohort 2: general population study; and cohort 3: non-diabetic population study). Urinary Pro-NT was assessed in part of the patients from cohort 1. In a 4th independent cohort, serum Pro-NT was further related to mortality in patients with advanced CKD. Tissue-specific Nts expression was further investigated in two mouse models of diabetic CKD and compared to non-diabetic control mice. RESULTS: Pro-NT significantly increased with deteriorating renal function (P < 0.001). In meta-analysis of cohorts 1-3, Pro-NT was significantly and independently associated with estimated glomerular filtration rate (P ≤ 0.002). Patients in the middle/high Pro-NT tertiles at baseline had a higher all-cause mortality compared to the low Pro-NT tertile (Hazard ratio: 2.11, P = 0.046). Mice with severe diabetic CKD did not show increased Nts mRNA expression in different tissues compared to control animals. CONCLUSIONS: Circulating Pro-NT is associated with impaired renal function in independent cohorts comprising 4715 subjects and is related to all-cause mortality in patients with end-stage kidney disease. Our human and rodent data are in accordance with the hypotheses that Pro-NT is eliminated by the kidneys and could potentially contribute to increased mortality observed in patients with CKD.

Association of serum 25-hydroxyvitamin D concentrations with sleep phenotypes in a German community sample.

BACKGROUND: Sleep disorders and vitamin D deficiency are among the most common health problems. Few studies investigated the effect of vitamin D on objectively recorded sleep with sound methodological quality and reasonable temporal proximity. OBJECTIVE: To investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) concentrations and objective sleep parameters assessed within close temporal proximity in a population-based sample. It is expected that higher serum 25(OH)D concentrations are associated with 1) better objective sleep outcomes (longer sleep duration, higher sleep efficiency, earlier mid-sleep time) and 2) more positive subjective sleep evaluations. METHODS: A subset of participants (n = 1045) from the LIFE-Adult-Study was analysed. Measurement of serum 25(OH)D vitamin was performed using an electrochemiluminescence immunoassay. Actigraphic assessments were performed using SenseWear Pro 3 devices. The following objective sleep parameters were calculated: total sleep duration, night sleep duration, night sleep efficiency, midsleep time and wake after sleep onset (WASO). Subjective sleep evaluations were assessed via questionnaire (sleep quality (PSQI), daytime sleepiness (ESS)). Data were analysed applying a multiple linear regression model with a stepwise approach. RESULTS: The regression models revealed significant associations of serum 25(OH)D concentration with night sleep duration and midsleep time. No association was found for total sleep duration and night sleep efficiency. Higher serum 25(OH)D concentration was further associated with shorter WASO in males but longer WASO in females. Moreover, serum 25(OH)D concentration did not show any significant association with subjective sleep quality and daytime sleepiness. CONCLUSION: The results indicate that a higher concentration of serum 25(OH)D is associated with longer and earlier night sleep. Although the present study was able to demonstrate an association between serum 25(OH)D concentration and objective sleep parameters, no conclusion about underlying mechanisms or causal inferences can be drawn.

Associations Between Anxiety, Body Mass Index, and Sex Hormones in Women.

Background: Several studies have shown a positive association between anxiety and obesity, particularly in women. We aimed to study whether sex hormone alterations related to obesity might play a role in this association. Patients and methods: Data for this study were obtained from a population-based cohort study (the LIFE-Adult-Study). A total of 3,124 adult women (970 premenopausal and 2,154 postmenopausal) were included into the analyses. The anxiety symptomatology was assessed using the GAD-7 questionnaire (cut-off ≥ 10 points). Sex hormones were measured from fasting serum samples. Results: We did not find significant differences in anxiety prevalence in premenopausal obese women compared with normal-weight controls (4.8% vs. 5.5%). Both obesity and anxiety symptomatology were separately associated with the same sex hormone alteration in premenopausal women: higher total testosterone level (0.97 ± 0.50 in obese vs. 0.86 ± 0.49 nmol/L in normal-weight women, p = 0.026 and 1.04 ± 0.59 in women with vs. 0.88 ± 0.49 nmol/L in women without anxiety symptomatology, p = 0.023). However, women with anxiety symptomatology had non-significantly higher estradiol levels than women without anxiety symptomatology (548.0 ± 507.6 vs. 426.2 ± 474.0 pmol/L), whereas obesity was associated with lower estradiol levels compared with those in normal-weight group (332.7 ± 386.5 vs. 470.8 ± 616.0 pmol/L). Women with anxiety symptomatology had also significantly higher testosterone and estradiol composition (p = 0.006). No associations of sex hormone levels and BMI with anxiety symptomatology in postmenopausal women were found. Conclusions: Although both obesity and anxiety symptomatology were separately associated with higher testosterone level, there was an opposite impact of anxiety and obesity on estradiol levels in premenopausal women. We did not find an evidence that the sex hormone alterations related to obesity are playing a significant role in anxiety symptomatology in premenopausal women. This could be the explanation why we did not find an association between obesity and anxiety. In postmenopausal women, other mechanisms seem to work than in the premenopausal group.

Testosterone imbalance may link depression and increased body weight in premenopausal women.

Accumulating evidence supports a link between depression and being overweight in women. Given previously reported sex differences in fat accumulation and depression prevalence, as well as the likely role of sex hormones in both overweight and mood disorders, we hypothesised that the depression-overweight association may be mediated by sex hormones. To this end, we investigated the association of being overweight with depression, and then considered the role of sex hormones in relation to being overweight and depression in a large population-based cohort. We included a total of 3124 women, 970 premenopausal and 2154 postmenopausal from the LIFE-Adult cohort study in our analyses. We evaluated associations between being overweight (BMI >25 kg/m2), sex hormone levels, and depressive symptomatology according to Centre for Epidemiologic Studies Depression (CES-D) scores, and explored mediation of depression in a mediation model. Being overweight was significantly associated with depressive symptoms in premenopausal but not postmenopausal women. Both premenopausal and postmenopausal overweight women had higher free testosterone levels compared with normal weight women. Premenopausal women with depressive symptomatology had higher free testosterone levels compared to women without. We found a significant mediation effect of depressive symptomatology in overweight premenopausal women through free testosterone level. These findings highlight the association between being overweight and depressed, and suggest that high free testosterone levels may play a significant role in depression of overweight premenopausal women. Based on this, pharmacological approaches targeting androgen levels in overweight depressed females, in particular when standard anti-depressive treatments fail, could be of specific clinical relevance.

Alcohol consumption is positively associated with fasting serum ghrelin in non-dependent adults: Results from the population-based LIFE-Adult-Study.

BACKGROUND: Animal experiments and studies in alcohol dependent patients indicate that ghrelin signaling in the brain is causally involved in the regulation of alcohol reward and intake. Increasing ghrelin levels enhances alcohol craving and intake, blocking ghrelin receptors abolishes these effects. If ghrelin is also involved in non-dependent alcohol consumption in humans, though, remains unknown. The aim was therefore to investigate the relationship between ghrelin serum levels and alcohol consumption in a large population-based sample. METHODS: Total ghrelin was determined after an overnight fast in 1666 subjects participating in a population-based cross-sectional study ('LIFE') including 10,000 adults. 1521 subjects were included in this analysis. Alcohol consumption was assessed using a food frequency questionnaire (FFQ). Multiple linear regression analyses and extreme group comparisons testing for statistical differences of alcohol consumption between the highest and lowest quartile according to ghrelin levels were performed. RESULTS: Alcohol consumption was positively associated with serum ghrelin; total sample: ß = 0.003, p = 0.002; men: ß = 0.005, p = 0.023; women: ß = 0.002, p = 0.007, adjusted for age, BMI and smoking status. Mean alcohol consumption in men/women belonging to the highest quartile of serum ghrelin levels (men: 21.5 (21.1) g/day; women: 7.5 (11.4) g/day) was considerably higher than in those belonging to the lowest quartile (men: 16.5 (19.3) g/day p < 0.002; women: 4.59 (10.7) g/day p = 0.0001). CONCLUSION: This is the first study showing that alcohol consumption is positively associated with serum ghrelin in a population-based sample. The study provides an initial indication that ghrelin is also involved in the regulation of alcohol consumption in non-dependent subjects.