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Background: Hyperthyroidism is known to induce a hypercoagulable state. It stimulates plasma levels of procoagulative factors and reduces fibrinolytic activity. So far most of the data have been derived from patients with endogenous hyperthyroidism with a wide variability in the underlying pathogenesis and severity of the disease. Objectives: In this study we experimentally induced thyrotoxicosis in healthy volunteers to explore the effects of thyroxine excess on the plasma proteome. Using a shotgun proteomics approach, the abundance of plasma proteins was monitored before, during and after thyrotoxicosis. Methods: Sixteen healthy male subjects were sampled at baseline, 4 and 8 weeks under 250 µg/day thyroxine p.o., as well as 4 and 8 weeks after stopping the application. Plasma proteins were analyzed after depletion of 6 high-abundance proteins (MARS6) by LC-ESI-MS/MS mass spectrometry. Mass spectrometric raw data were processed using a label-free, intensity-based workflow. Subsequently, the linear dependence between protein abundances and fT<sub>4</sub> levels were calculated using a Pearson correlation. Results: All subjects developed biochemical thyrotoxicosis, and this effect was reversed within the first 4 weeks of follow-up. None of the volunteers noticed any subjective symptoms. Levels of 10 proteins involved in the coagulation cascade specifically correlated with fT<sub>4</sub>, supporting an influence of thyroid hormone levels on blood coagulation even at nonpathological levels. Conclusions: The results suggest that experimental thyrotoxicosis exerts selective and specific thyroxine-induced effects on coagulation markers. Our study design allows assessment of thyroid hormone effects on plasma protein levels without secondary effects of other diseases or therapies.
Objective
This study provides a comprehensive overview of the associations of five adipokines (adiponectin, chemerin, galectin‐3, leptin, and resistin) with fat deposits, behavioral risk factors, and metabolic phenotypes.
Methods
Using multivariable linear and logistic regression models, cross‐sectional data from 4,116 participants of the population‐based Study of Health in Pomerania were analyzed.
Results
Participants with obesity showed higher chemerin, galectin‐3, and leptin but showed lower adiponectin concentrations. Independently of other fat compounds, liver fat content, visceral adipose tissue, and subcutaneous adipose tissue (SAT) were inversely associated with adiponectin. Independent positive associations of liver fat content and SAT with chemerin as well as of SAT with galectin‐3 and leptin were observed. Physically inactive participants had higher chemerin and leptin concentrations. Smokers had higher chemerin and galectin‐3 as well as lower leptin. Alcohol consumption was associated with adiponectin (positive) and resistin (inverse). All adipokines were associated with at least one lipid marker. Associations with glucose metabolism were seen for adiponectin, chemerin, galectin‐3, and leptin.
Conclusions
High adiponectin concentrations were related to favorable metabolic conditions, whereas high chemerin, galectin‐3, and leptin were associated with an unfavorable metabolic profile. High leptin seems to be primarily indicative of obesity, whereas high adiponectin and chemerin are associated with a broader range of metabolic phenotypes.
Das Immunsystem hat die Aufgabe körperfremde von körpereigenen Strukturen zu unterscheiden. Es gewährt dem Organismus die spezifische Abwehr gegenüber krankheitsauslösenden Strukturen (Bakterien, Viren, Gifte). In seiner Komplexität führen Fehlfunktionen des Immunsystems zu verschiedenen Erkrankungen. Richtet sich die Immunantwort gegen körpereigene Strukturen und versagt die Unterscheidung zwischen Eigen und Fremd, so spricht man von Autoimmunerkrankungen. Die vorliegende Arbeit beschäftigte sich mit der Epidemiologie von (1) Allergien und (2) Autoimmunerkrankungen der Schilddrüse (AIT). (1) Parodontitis und Allergien HINTERGRUND: Parodontitis ist eine unter Erwachsenen weit verbreitete lokale, orale Infektion, die systemische Auswirkungen hat. In der Ätiologie von Allergien wird seit den 80iger Jahren die sogenannte Hygiene-Hypothese diskutiert. Diese besagt, dass Infektionen im Kindesalter präventiv auf die Entstehung von Allergien wirken. In der vorliegenden Studie wurde der Zusammenhang zwischen Parodontitis und allergischen Erkrankungen (Heuschnupfen, Hausstauballergie und Asthma) in der Allgemeinbevölkerung Vorpommerns und einem Diabetes mellitus Typ 1 Patientenkollektiv untersucht. METHODEN: Für die erste Analyse wurden Daten von 2837 Männern und Frauen im Alter zwischen 20 und 59 Jahren aus der bevölkerungsrepräsentativen „Study of Health in Pomerania“ (SHIP) herangezogen. Das Diabetes mellitus Typ 1 Patientenkollektiv beinhaltete 170 Patienten im Alter zwischen 17 und 80 Jahren. Der Attachmentverlust (AV) wurde gemessen und das Ausmaß der Parodontitis mittels des Prozentsatzes an Fläche mit einem AV über 3mm erfasst (gesunder Parodontalstatus, geringer AV, moderater AV, schwerwiegender AV). ERGEBNISSE: In SHIP berichteten 326 Personen Heuschnupfen, 111 Personen eine Hausstauballergie und 114 Personen waren von Asthma betroffen. In dem untersuchten Diabetes mellitus Typ 1 Patientenkollektiv litten 22 Patienten an mindestens einer der drei allergischen Erkrankungen. In SHIP wurde nach Kontrolle für ausgewählte Konfounder ein inverser Zusammenhang zwischen dem Schweregrad der Parodontitis und dem Vorhandensein von Heuschnupfen sowie Hausstauballergie gefunden. Mit steigendem AV nahm die Wahrscheinlichkeit für Heuschnupfen (ptrend<0,05) und Hausstauballergie (ptrend<0,05) ab. Hinsichtlich Asthma zeigte sich kein signifikanter Trend (ptrend=0,11), jedoch konnte auch hier mit steigendem AV eine gleichzeitige Abnahme der Wahrscheinlichkeit für das Auftreten von Asthma beobachtet werden. Die Analysen im Diabetes mellitus Typ 1 Patientenkollektiv bestätigten diese Ergebnisse. Auch hier nahm die Wahrscheinlichkeit für das Auftreten einer Allergie mit zunehmenden AV ab. FAZIT: Sowohl in der Allgemeinbevölkerung Vorpommerns als auch in Diabetes mellitus Typ 1 Patienten wurde eine inverse Assoziation zwischen dem Parodontalstatus und allergischen Erkrankungen dargelegt. Diese Ergebnisse befürworten die Hygiene-Hypothese. (2) Anzahl an Schwangerschaften und AIT HINTERGRUND: Frauen sind häufiger von AIT betroffen als Männer. Darüber hinaus ist bekannt, dass das Risiko für einen AIT während der Schwangerschaft und in der Post-Partum-Periode steigt. Das Ziel der Analysen war es, die Assoziation zwischen der Anzahl an Schwangerschaften und AIT zu untersuchen. METHODEN: Daten von 2837 Frauen im Alter zwischen 20 und 79 Jahren aus der bevölkerungsrepräsentativen „Study of Health in Pomerania“ (SHIP) wurden analysiert. Serum Anti-Thyreoperoxidase-Antikörper (anti-TPO) und Thyrotropin Titer wurden bestimmt. Weiterhin wurde eine Schilddrüsensonographie durchgeführt. Eine AIT lag beim gleichzeitigen Vorliegen eines echoarmen Schilddrüsenmusters und eines positiven anti-TPO Titers (>200 IU/ml) vor. ERGEBNISSE: Multivariable Zusammenhangsanalysen zeigten, dass die Chance für eine AIT (OR 4,7 [95%-KI 1,4-15,6], p<0,05) bei Frauen mit mindestens einer Schwangerschaft im Vergleich zu Frauen, die niemals schwanger waren, erhöht war. Ähnliche Ergebnisse zeigten sich auch für ein echoarmes Schilddrüsenmuster (OR 1,7 [95%-KI 1,0-2,8], p<0,05) und positive anti-TPO Werte (OR 1,9 [95%-KI 1,0-3,3], p<0,05). FAZIT: In der untersuchten Studienpopulation stieg das Risiko für eine AIT mit dem Durchleben der ersten Schwangerschaft an.
Sex-specific associations of cardiorespiratory fitness and galectin-3 in the general population
(2022)
Aims
Low cardiorespiratory fitness (CRF) is associated with greater mortality and morbidity. Galectin-3 (Gal-3) is a prognostic biomarker for fibrosis and heart failure. Gal-3 is also associated with a greater risk for cardiovascular mortality. Whether CRF is related with Gal-3 is unclear. The objective of this study was to assess the sex-specific associations of CRF and Gal-3 levels in the general population.
Methods
Gal-3 concentrations were determined using a sandwich enzyme immunoassay in the population-based Study of Health in Pomerania (SHIP-TREND-0). Sex-stratified linear regression models adjusted for age, current smoking status, and renal function were used. Individuals with left ventricular ejection fraction (LVEF) <40%, previous myocardial infarction, atrial fibrillation, chronic lung disease, severe renal disease (estimated glomerular filtration rate <30 mL/min/mm2), a history of cancer, and extreme values for Gal-3 (<1st percentile; >99th percentile) were excluded.
Results
A total of n = 1515 participants with a median age of 49 (IQR: 39–60 years, 48% males) were included. In men, a 1 L/min greater VO2peak was significantly related to 0.50 ng/mL (95% CI −0.8068 to −0.1938, P < 0.01) less Gal-3. In males, a 1 mL/min/kg higher VO2peak adjusted for body weight was associated with −0.0286 ng/mL (95% CI −0.0052 to −0.0005, P = 0.02) less Gal-3. When VO2peak was adjusted for lean mass 1 mL/kg/min more was correlated with a −0.0022 ng/mL (95% CI −0.0043 to -0.0007, P = 0.04) less Gal-3. In women, VO2peak (β −0.2046 95% CI −0.6541 to 0.2449, P = 0.37) and VO2peak adjusted for lean mass (β −0.0019 95% CI −0.0421 to –0.0050, P = 0.12) were not related with Gal-3, whereas a 1 mL/min/kg higher VO2peak adjusted for body weight was significantly associated with a −0.0064 ng/mL lower Gal-3 (95% CI −0.0092 to -0.0035, P < 0.01). There were no differences between pre-menopausal and post-menopausal women.
Conclusions
VO2peak was associated with Gal-3 only in men, but VO2peak adjusted for body weight in women and men. Our results suggest that the adverse consequences of low CRF may be mediated by Gal-3. Further research is needed to understand the sex-specific association between CRF and Gal-3 and whether they are clinically relevant.
Background: Chronic kidney disease (CKD) and low serum total testosterone (TT) concentrations are independent predictors of mortality risk in the general population, but their combined potential for improved mortality risk stratification is unknown. Methods: We used data of 1,822 men from the population-based Study of Health in Pomerania followed- up for 9.9 years (median). The direct effects of kidney dysfunction (estimated glomerular filtration rate <60 ml/min/ 1.73 m<sup>2</sup>), albuminuria (urinary albumin-creatinine ratio ≧2.5 mg/mmol) and their combination (CKD) on all-cause and cardiovascular mortality were analyzed using multivariable Cox regression models. Serum TT concentrations below the age-specific 10th percentile (by decades) were considered low and were used for further risk stratification. Results: Kidney dysfunction (hazard ratio, HR, 1.40; 95% confidence interval, CI, 1.02–1.92), albuminuria (HR, 1.38; 95% CI, 1.06–1.79), and CKD (HR, 1.42; 95% CI, 1.09–1.84) were associated with increased all-cause mortality risk, while only kidney dysfunction (HR, 2.01; 95% CI, 1.21–3.34) was associated with increased cardiovascular mortality risk after multivariable adjustment. Men with kidney dysfunction and low TT concentrations were identified as high-risk individuals showing a more than 2-fold increased all-cause mortality risk (HR, 2.52; 95% CI, 1.08–5.85). Added to multivariable models, nonsignificant interaction terms suggest that kidney dysfunction and low TT are primarily additive rather than synergistic mortality risk factors. Conclusion: In the case of early loss of kidney function, measured TT concentrations might help to detect high-risk individuals for potential therapeutic interventions and to improve mortality risk assessment and outcome.
For the goal of individualized medicine, it is critical to have clinical phenotypes at hand which represent the individual pathophysiology. However, for most of the utilized phenotypes, two individuals with the same phenotype assignment may differ strongly in their underlying biological traits. In this paper, we propose a definition for individualization and a corresponding statistical operationalization, delivering thereby a statistical framework in which the usefulness of a variable in the meaningful differentiation of individuals with the same phenotype can be assessed. Based on this framework, we develop a statistical workflow to derive individualized phenotypes, demonstrating that under specific statistical constraints the prediction error of prediction scores contains information about hidden biological traits not represented in the modeled phenotype of interest, allowing thereby internal differentiation of individuals with the same assigned phenotypic manifestation. We applied our procedure to data of the population-based Study of Health in Pomerania to construct a refined definition of obesity, demonstrating the utility of the definition in prospective survival analyses. Summarizing, we propose a framework for the individualization of phenotypes aiding personalized medicine by shifting the focus in the assessment of prediction models from the model fit to the informational content of the prediction error.
Microbial metabolites measured using NMR may serve as markers for physiological or pathological host–microbe interactions and possibly mediate the beneficial effects of microbiome diversity. Yet, comprehensive analyses of gut microbiome data and the urine NMR metabolome from large general population cohorts are missing. Here, we report the associations between gut microbiota abundances or metrics of alpha diversity, quantified from stool samples using 16S rRNA gene sequencing, with targeted urine NMR metabolites measures from 951 participants of the Study of Health in Pomerania (SHIP). We detected significant genus–metabolite associations for hippurate, succinate, indoxyl sulfate, and formate. Moreover, while replicating the previously reported association between hippurate and measures of alpha diversity, we identified formate and 4-hydroxyphenylacetate as novel markers of gut microbiome alpha diversity. Next, we predicted the urinary concentrations of each metabolite using genus abundances via an elastic net regression methodology. We found profound associations of the microbiome-based hippurate prediction score with markers of liver injury, inflammation, and metabolic health. Moreover, the microbiome-based prediction score for hippurate completely mediated the clinical association pattern of microbial diversity, hinting at a role of benzoate metabolism underlying the positive associations between high alpha diversity and healthy states. In conclusion, large-scale NMR urine metabolomics delivered novel insights into metabolic host–microbiome interactions, identifying pathways of benzoate metabolism as relevant candidates mediating the beneficial health effects of high microbial alpha diversity.
The Study of Health in Pomerania (SHIP), a population-based study from a rural state in northeastern Germany with a relatively poor life expectancy, supplemented its comprehensive examination program in 2008 with whole-body MR imaging at 1.5 T (SHIP-MR). We reviewed more than 100 publications that used the SHIP-MR data and analyzed which sequences already produced fruitful scientific outputs and which manuscripts have been referenced frequently. Upon reviewing the publications about imaging sequences, those that used T1-weighted structured imaging of the brain and a gradient-echo sequence for R2* mapping obtained the highest scientific output; regarding specific body parts examined, most scientific publications focused on MR sequences involving the brain and the (upper) abdomen. We conclude that population-based MR imaging in cohort studies should define more precise goals when allocating imaging time. In addition, quality control measures might include recording the number and impact of published work, preferably on a bi-annual basis and starting 2 years after initiation of the study. Structured teaching courses may enhance the desired output in areas that appear underrepresented.
Aim
To investigate the medium-term associations of serum protein subfractions derived from proton nuclear magnetic resonance (1H-NMR) spectroscopy with periodontitis and tooth loss.
Materials and Methods
A total of 3031 participants of the cohort Study of Health in Pomerania (SHIP-TREND) were included. In addition to conventional serum testing, serum lipoprotein contents and subfractions were analysed by 1H-NMR spectroscopy. Confounder-adjusted associations of lipoprotein variables with periodontitis and the number of missing teeth variables were analysed using mixed-effects models with random intercepts for time across individuals, accounting for multiple testing.
Results
While only spurious associations between lipoprotein levels from conventional blood tests were found—that is, triglycerides were associated with mean clinical attachment level (CAL) and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio with the number of missing teeth - several associations emerged from serum lipoprotein subfractions derived from 1H-NMR analysis. Specifically, elevated LDL triglycerides were associated with higher levels of mean probing depth (PD), mean CALs, and increased odds of having <20 teeth. HDL-4 cholesterol levels were inversely associated with mean PD. Systemic inflammation (C-reactive protein) might mediate the effects of LDL and HDL triglyceride contents on periodontitis severity.
Conclusions
Several associations between serum lipoprotein subfractions and periodontitis were observed. As the underlying biochemical mechanisms remain unclear, further research is needed.
Background
Lower cortisol concentrations in adulthood were repeatedly associated with more severe childhood maltreatment. Additionally, childhood maltreatment was reported to promote health risk behavior, such as smoking or alcohol consumption, and to increase the risk of mental and somatic diseases during adulthood, such as major depressive disorders or obesity. The present study investigated if health risk behavior and disease symptoms in adults mediate the associations between past childhood maltreatment and present basal serum cortisol concentrations.
Methods
Data from two independent adult cohorts of the general population-based Study of Health in Pomerania (SHIP-TREND-0: N = 3,517; SHIP-START-2: N = 1,640) was used. Childhood maltreatment was assessed via the Childhood Trauma Questionnaire (CTQ). Cortisol concentrations were measured in single-point serum samples. Health risk behavior and mental and physical symptoms were used as mediators. Mediation analyses were calculated separately for both cohorts; results were integrated via meta-analyses.
Results
In mediator-separated analyses, associations between childhood maltreatment and basal serum cortisol concentrations were partly mediated by depressive symptoms (BDI-II: βindirect effect = -.011, pFDR = .017, 21.0% mediated) and subjective somatic health complaints (somatic complaints: βindirect effect = -.010, pFDR = .005, 19.4% mediated). In the second step, both mediators were simultaneously integrated into one mediation model. The model replicated the mediation effects of the subjective somatic health complaints (whole model: βindirect effect = -.014, p = .001, 27.6% mediated; BDI-II: βindirect effect = -.006, p = .163, 11.4% mediated, somatic complaints: βindirect effect = -.020, p = .020, 15.5% mediated).
Conclusion
The results support the hypothesis that the long-lasting effects of childhood maltreatment on the stress response system are partly mediated through self-perceived disease symptoms. However, no mediation was found for health risk behavior or physically measured mediators. Mediation models with multiple simultaneous mediators pointed to a relevant overlap between the potential mediators. This overlap should be focused on in future studies.
Background: The global obesity epidemic is a major public health concern, and accurate diagnosis is essential for identifying at-risk individuals. Three-dimensional (3D) body scanning technology offers several advantages over the standard practice of tape measurements for diagnosing obesity. This study was conducted to validate body scan data from a German population-based cohort and explore clinical implications of this technology in the context of metabolic syndrome. Methods: We performed a cross-sectional analysis of 354 participants from the Study of Health in Pomerania that completed a 3D body scanning examination. The agreement of anthropometric data obtained from 3D body scanning with manual tape measurements was analyzed using correlation analysis and Bland–Altman plots. Classification agreement regarding abdominal obesity based on IDF guidelines was assessed using Cohen’s kappa. The association of body scan measures with metabolic syndrome components was explored using correlation analysis. Results: Three-dimensional body scanning showed excellent validity with slightly larger values that presumably reflect the true circumferences more accurately. Metabolic syndrome was highly prevalent in the sample (31%) and showed strong associations with central obesity. Using body scan vs. tape measurements of waist circumference for classification resulted in a 16% relative increase in the prevalence of abdominal obesity (61.3% vs. 52.8%). Conclusions: These results suggest that the prevalence of obesity may be underestimated using the standard method of tape measurements, highlighting the need for more accurate approaches.
Periodontitis is one of the most prevalent oral diseases worldwide and is caused by multifactorial interactions between host and oral bacteria. Altered cellular metabolism of host and microbes releases a number of intermediary end products known as metabolites. There is an increasing interest in identifying metabolites from oral fluids such as saliva to widen the understanding of the complex pathogenesis of periodontitis. It is believed that some metabolites might serve as indicators toward early detection and screening of periodontitis and perhaps even for monitoring its prognosis in the future. Because contemporary periodontal screening methods are deficient, there is an urgent need for novel approaches in periodontal screening procedures. To this end, we associated oral parameters (clinical attachment level, periodontal probing depth, supragingival plaque, supragingival calculus, number of missing teeth, and removable denture) with a large set of salivary metabolites (n = 284) obtained by mass spectrometry among a subsample (n = 909) of nondiabetic participants from the Study of Health in Pomerania (SHIP-Trend-0). Linear regression analyses were performed in age-stratified groups and adjusted for potential confounders. A multifaceted image of associated metabolites (n = 107) was revealed with considerable differences according to age groups. In the young (20 to 39 y) and middle-aged (40 to 59 y) groups, metabolites were predominantly associated with periodontal variables, whereas among the older subjects (≥60 y), tooth loss was strongly associated with metabolite levels. Metabolites associated with periodontal variables were clearly linked to tissue destruction, host defense mechanisms, and bacterial metabolism. Across all age groups, the bacterial metabolite phenylacetate was significantly associated with periodontal variables. Our results revealed alterations of the salivary metabolome in association with age and oral health status. Among our comprehensive panel of metabolites, periodontitis was significantly associated with the bacterial metabolite phenylacetate, a promising substance for further biomarker research.
Our goal was to provide a comprehensive overview of the antibody response to Staphylococcus aureus antigens in the general population as a basis for defining disease-specific profiles and diagnostic signatures. We tested the specific IgG and IgA responses to 79 staphylococcal antigens in 996 individuals from the population-based Study of Health in Pomerania. Using a dilution-based multiplex suspension array, we extended the dynamic range of specific antibody detection to seven orders of magnitude, allowing the precise quantification of high and low abundant antibody specificities in the same sample. The observed IgG and IgA antibody responses were highly heterogeneous with differences between individuals as well as between bacterial antigens that spanned several orders of magnitude. Some antigens elicited significantly more IgG than IgA and vice versa. We confirmed a strong influence of colonization on the antibody response and quantified the influence of sex, smoking, age, body mass index, and serum glucose on anti-staphylococcal IgG and IgA. However, all host parameters tested explain only a small part of the extensive variability in individual response to the different antigens of S. aureus.
Abstract
Study Objective
Long‐term intake of proton pump inhibitors (PPIs) might increase the risk of cardiovascular events. One suggested mechanism is that PPIs inhibit the enzyme dimethylarginine dimethylaminohydrolase (DDAH) and thereby block the degradation of endothelial asymmetrical dimethylarginine (ADMA). Excess ADMA in turn leads to impaired endothelial nitric oxide (NO) generation. So far, this mechanism has only been established in human cell cultures. Previous studies that examined this pathway in human populations measured circulating ADMA and found no association with PPI use and excess plasma ADMA. But in a recent study, plasma ADMA was not correlated with intracellular ADMA. We therefore focused on changes in plasma citrulline as an indicator for potential DDAH inhibition.
Design
We analyzed the association between regular daily PPI intake and flow‐mediated dilation (FMD) of the brachial artery as well as plasma concentrations of citrulline, arginine, ADMA, and symmetric dimethylarginine using inverse probability weighting to adjust for confounding and censoring.
Data Source
Data of 1298 participants from two independent cohorts of the population‐based Study of Health in Pomerania were used.
Participants
Participants of the population‐based Study of Health in Pomerania are a stratified random sample of the study region.
Exposure
Regular daily intake of PPIs.
Measurements
FMD of the brachial artery and plasma concentrations of citrulline, arginine, ADMA, and symmetric dimethylarginine.
Main Results
Eighty‐seven participants (57.5% female) were regular daily users of PPIs. In the fully adjusted models, associations were identified for FMD and plasma citrulline concentrations. PPI users revealed a 0.99% (95% CI: −1.96 to −0.02) lower FMD and 3.03 µmol/L (95% CI: −4.96 to −1.10) lower plasma citrulline levels as compared to non‐users.
Conclusion
Our data provide evidence that long‐term intake of PPIs might inhibit human DDAH activity, resulting in impaired endothelial NO production and reduced vascular function. In the long run, this might explain an increased risk for cardiovascular diseases associated with long‐term PPI use.
Background and objectives
Various cross-sectional studies have observed an association between high circulating concentrations of the adipokine chemerin and an unfavorable metabolic profile. However, the prognostic value of chemerin for the risk of associated diseases and mortality was examined only in a few studies mostly using small and highly selected patient populations. We aimed to analyze the association between plasma chemerin concentrations and all-cause as well as cause-specific mortality in the general population.
Study design and methods
From the Study of Health in Pomerania (SHIP), participants of two independent cohorts (SHIP-START-1 [n = 3037], SHIP-TREND-0 [n = 4193]) were followed up for 15 and 9 years (median), respectively. The association between plasma chemerin and all-cause mortality was analyzed using multivariable Cox proportional hazard regression models. Additionally, cause-specific hazards for cardiovascular disease (CVD) and cancer mortality were modeled considering competing events.
Results
A total number of 507 and 208 deaths occurred during follow-up in SHIP-START-1 and SHIP-TREND-0, respectively. Multivariable regression analyses revealed a significant association between high plasma chemerin concentrations and greater overall mortality that was independent of major confounders. Each 30 ng/mL increase in chemerin was associated with a 17% higher risk of all-cause mortality (95%-confidence interval: 1.10–1.26). Cause-specific analyses further showed that the chemerin concentration was significantly associated with cancer mortality but not with CVD mortality.
Conclusion
The present study detected a positive association between plasma chemerin concentrations and all-cause mortality in a large population-based study sample. Cause-specific analyses have shown that chemerin is likely to play a decisive role in cancer-related deaths. However, a direct association with cardiovascular mortality could not be established.
Context: 3,5-Diiodo-<smlcap>L</smlcap>-thyronine (3,5-T<sub>2</sub>) is a thyroid hormone metabolite which exhibited versatile effects in rodent models, including the prevention of insulin resistance or hepatic steatosis typically forced by a high-fat diet. With respect to euthyroid humans, we recently observed a putative link between serum 3,5-T<sub>2</sub> and glucose but not lipid metabolism. Objective: The aim of the present study was to widely screen the urine metabolome for associations with serum 3,5-T<sub>2</sub> concentrations in healthy individuals. Study Design and Methods: Urine metabolites of 715 euthyroid participants of the population-based Study of Health in Pomerania (SHIP-TREND) were analyzed by <sup>1</sup>H-NMR spectroscopy. Multinomial logistic and multivariate linear regression models were used to detect associations between urine metabolites and serum 3,5-T<sub>2</sub> concentrations. Results: Serum 3,5-T<sub>2</sub> concentrations were positively associated with urinary levels of trigonelline, pyroglutamate, acetone and hippurate. In detail, the odds for intermediate or suppressed serum 3,5-T<sub>2</sub> concentrations doubled owing to a 1-standard deviation (SD) decrease in urine trigonelline levels, or increased by 29-50% in relation to a 1-SD decrease in urine pyroglutamate, acetone and hippurate levels. Conclusion: Our findings in humans confirmed the metabolic effects of circulating 3,5-T<sub>2</sub> on glucose and lipid metabolism, oxidative stress and enhanced drug metabolism as postulated before based on interventional pharmacological studies in rodents. Of note, 3,5-T<sub>2</sub> exhibited a unique urinary metabolic profile distinct from previously published results for the classical thyroid hormones.
Background and aims
Prevention measures for cardiovascular diseases (CVD) have shifted their focus from lipoproteins to the immune system. However, low-grade inflammation and dyslipidemia are tightly entangled. The objective of this study was to assess the relations between a broad panel of inflammatory biomarkers and lipoprotein subclass parameters.
Methods
We utilized data from the population-based Study of Health in Pomerania (SHIP-TREND, n = 403). Plasma concentrations of 37 inflammatory markers were measured by a bead-based assay. Furthermore, we employed nuclear magnetic resonance spectroscopy to measure total cholesterol, total triglycerides, total phospholipids as well as the fractional concentrations of cholesterol, triglycerides, phospholipids, ApoA1, ApoA2 and ApoB in all major lipoprotein subclasses. Associations between inflammatory biomarkers and lipoprotein subclasses were analyzed by adjusted linear regression models.
Results
APRIL, BAFF, TWEAK, sCD30, Pentraxin-3, sTNFR1, sTNFR2, Osteocalcin, Chitinase 3-like 1, IFN-alpha2, IFN-gamma, IL-11, IL-12p40, IL-29, IL-32, IL-35, TSLP, MMP1 and MMP2 were related with lipoprotein subclass components, forming two distinct clusters. APRIL had inverse relations to HDL-C (total and subclasses) and HDL Apo-A1 and Apo-A2 content. MMP-2 was inversely related to VLDL-C (total and subclasses), IDL-C as well as LDL5/6-C and VLDL-TG, IDL-TG, total triglycerides as well as LDL5/5-TG and HDL4-TG. Additionally, we identified a cluster of cytokines linked to the Th1-immune response, which were associated with an atherogenic lipoprotein profile.
Conclusion
Our findings expand the existing knowledge of inflammation-lipoprotein interactions, many of which are suggested to be involved in the pathogeneses of chronic non-communicable diseases. The results of our study support the use of immunomodulatory substances for the treatment and possibly prevention of CVD.