Augsburg Study Research Articles

The Association between Serum Bilirubin Levels and Colorectal Cancer Risk: Results from the Prospective Cooperative Health Research in the Region of Augsburg (KORA) Study in Germany.

Emerging studies have suggested that bilirubin, particularly unconjugated bilirubin (UCB), has substantial anti-inflammatory and antioxidant properties that protect against oxidative stress-associated diseases such as cancer. Few observational studies have investigated the etiological role of bilirubin in colorectal cancer (CRC) development. In this case-control study, nested in the population-based prospective cohort of the Cooperative Health Research in the Region of Augsburg (KORA) study in south Germany, pre-diagnostic circulating UCB concentrations were measured by high-performance liquid chromatography in 77 CRC cases and their individually matched controls. Multivariable unconditional logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for associations between log-transformed UCB levels (log-UCB), standardized per one-standard-deviation (one-SD) increment, and CRC risk. The models were a priori stratified by sex based on previous evidence. In the fully adjusted models, each one-SD increment in log-UCB was indicative of a positive association with CRC risk (OR, 1.20; 95% CI, 0.52–2.79) among men, and of an inverse association (OR, 0.76; 95% CI, 0.34–1.84) among women (Pheterogeneity = 0.4 for differences between men and women). We found little evidence for sex-specific associations of circulating bilirubin with CRC risk, and further studies are needed to confirm or refute the potential associations.

Toward targeted prevention: risk factors for prediabetes defined by impaired fasting glucose, impaired glucose tolerance and increased HbA1c in the population-based KORA study from Germany

AimsTo identify socioeconomic, behavioral and clinical factors that are associated with prediabetes according to different prediabetes definition criteria.MethodsAnalyses use pooled data of the population-based Cooperative Health Research in the Region of Augsburg (KORA) studies (n = 5312 observations aged ≥ 38 years without diabetes). Prediabetes was defined through either impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or elevated HbA1c according to thresholds of the American Diabetes Association. Explanatory variables were regressed on prediabetes using generalized estimating equations.ResultsMean age was 58.4 years; 50% had prediabetes (33% had IFG, 16% IGT, and 26% elevated HbA1c, 10% fulfilled all three criteria). Age, obesity, hypertension, low education, unemployment, statutory health insurance, urban residence and physical inactivity were associated with prediabetes. Male sex was a stronger risk factor for IFG (OR = 2.5; 95%–CI: 2.2–2.9) than for IGT or elevated HbA1c, and being unemployed was a stronger risk factor for IGT (OR = 3.2 95%–CI: 2.6–4.0) than for IFG or elevated HbA1c.ConclusionsThe overlap of people with IFG, IGT and elevated HbA1c is small, and some factors are associated with only one criterion. Knowledge on sociodemographic and socioeconomic risk factors can be used to effectively target interventions to people at high risk for type 2 diabetes.

Trends in cancer incidence and survival in the Augsburg study region—results from the Augsburg cancer registry

ObjectivesKnowledge about time trends of cancer incidence and cancer survival in a defined region is an essential prerequisite for the planning of regional healthcare infrastructure. The aim of the study...

Long-Term Outcomes in Patients with Stroke after in-Hospital Treatment-Study Protocol of the Prospective Stroke Cohort Augsburg (SCHANA Study).

Introduction: In Germany, stroke is the third leading cause of death, with more than 60,000 fatalities out of approximately 260,000 cases (first-ever and recurrent strokes) each year. So far, there are only a few long-term studies investigating determinants of the natural course of the disease, especially in the era of mechanical thrombectomy. Materials and Methods: The prospective single-center stroke cohort Augsburg (SCHANA) study will include about 1000 patients treated for stroke in the University Hospital of Augsburg. Patients aged 18 years or older with a confirmed diagnosis of ischemic or hemorrhagic stroke are included in the study. Information on demographic characteristics, onset of symptoms, etiologic factors, comorbidities, quality of life, invasive and non-invasive treatment, complications, and laboratory parameters are collected during a personal interview conducted during the patients’ hospital stay and via a medical chart review. About 30 mL of blood is collected from each patient, and after processing and aliquoting, all blood specimens are frozen at −80° C. The study participants will be followed-up via postal questionnaires at three and 12 months after discharge from the hospital. Furthermore, mortality follow-ups will be conducted. Cox-regression analysis will be used to estimate relative risks. Conclusion: The SCHANA study will generate comprehensive data on the long-term course of the disease. In addition to the main outcomes, recurrent events and survival, patient-oriented outcomes such as health-related quality of life and depression are the focus of the study.

Long-term outcomes in patients with severe depression after in-hospital treatment – study protocol of the depression long-term Augsburg (DELTA) study

IntroductionDepressive disorders are very common diseases entailing a great burden on affected people. However, comprehensive information on long-term disease course in patients with severe depression is lacking so far. The...

Long-term outcomes in patients with acute pulmonary embolism after in-hospital treatment: study protocol of the prospective Lungenembolie Augsburg Studie (LEA study)

IntroductionAcute pulmonary embolism (PE) is a frequent life-threatening event and an important cause of hospitalisation, morbidity and mortality worldwide. Limited information on the long-term course of PE patients is available...

Methylome-wide association study provides evidence of particulate matter air pollution-associated DNA methylation

BackgroundDNA methylation (DNAm) may contribute to processes that underlie associations between air pollution and poor health. Therefore, our objective was to evaluate associations between DNAm and ambient concentrations of particulate matter (PM) ≤2.5, ≤10, and 2.5–10 μm in diameter (PM2.5; PM10; PM2.5–10). MethodsWe conducted a methylome-wide association study among twelve cohort- and race/ethnicity-stratified subpopulations from the Women's Health Initiative and the Atherosclerosis Risk in Communities study (n = 8397; mean age: 61.5 years; 83% female; 45% African American; 9% Hispanic/Latino American). We averaged geocoded address-specific estimates of daily and monthly mean PM concentrations over 2, 7, 28, and 365 days and 1 and 12 months before exams at which we measured leukocyte DNAm in whole blood. We estimated subpopulation-specific, DNAm-PM associations at approximately 485,000 Cytosine-phosphate-Guanine (CpG) sites in multi-level, linear, mixed-effects models. We combined subpopulation- and site-specific estimates in fixed-effects, inverse variance-weighted meta-analyses, then for associations that exceeded methylome-wide significance and were not heterogeneous across subpopulations (P < 1.0 × 10−7; PCochran's Q > 0.10), we characterized associations using publicly accessible genomic databases and attempted replication in the Cooperative Health Research in the Region of Augsburg (KORA) study. ResultsAnalyses identified significant DNAm-PM associations at three CpG sites. Twenty-eight-day mean PM10 was positively associated with DNAm at cg19004594 (chromosome 20; MATN4; P = 3.33 × 10−8). One-month mean PM10 and PM2.5–10 were positively associated with DNAm at cg24102420 (chromosome 10; ARPP21; P = 5.84 × 10−8) and inversely associated with DNAm at cg12124767 (chromosome 7; CFTR; P = 9.86 × 10−8). The PM-sensitive CpG sites mapped to neurological, pulmonary, endocrine, and cardiovascular disease-related genes, but DNAm at those sites was not associated with gene expression in blood cells and did not replicate in KORA. ConclusionsAmbient PM concentrations were associated with DNAm at genomic regions potentially related to poor health among racially, ethnically and environmentally diverse populations of U.S. women and men. Further investigation is warranted to uncover mechanisms through which PM-induced epigenomic changes may cause disease.

Persistent organic pollutants and the incidence of type 2 diabetes in the CARLA and KORA cohort studies

BackgroundAssociations between several persistent organic pollutants (POPs) and type 2 diabetes have been found in humans, but the relationship has rarely been investigated in the general population. The current nested case-control study examined internal exposure to polychlorinated biphenyls (PCB) and pesticides and the incidence of type 2 diabetes among participants of two population-based German cohort studies. MethodsWe retrospectively selected 132 incident cases of type 2 diabetes and 264 age- and sex-matched controls from the CARdiovascular Living and Aging in Halle (CARLA) study (2002–2006, East Germany) and the Cooperative Health Research in the Region of Augsburg (KORA) study (1999–2001, South Germany) based on diabetes status at follow-up examinations in 2007–2010 and 2006–08, respectively (60% male, mean age 63 and 54 years). We assessed the association between baseline POP concentrations and incident diabetes by conditional logistic regression adjusted for cohort, BMI, cholesterol, alcohol, smoking, physical activity, and parental diabetes. Additionally, we examined effect modification by sex, obesity, parental diabetes and cohort. ResultsIn both cohorts, diabetes cases showed a higher BMI, a higher frequency of parental diabetes, and higher levels of POPs. We observed an increased chance for incident diabetes for PCB-138 and PCB-153 with an odds ratio (OR) of 1.50 (95%CI: 1.07–2.11) and 1.53 (1.15–2.04) per interquartile range increase in the respective POP. In addition, explorative results suggested higher OR for women and non-obese participants. ConclusionsOur results add to the evidence on diabetogenic effects of POPs in the general population, and warrant both policies to prevent human exposure to POPs and additional research on the adverse effects of more complex chemical mixtures.

Metabolomics Identifies Novel Blood Biomarkers of Pulmonary Function and COPD in the General Population.

Determination of metabolomic signatures of pulmonary function and chronic obstructive pulmonary disease (COPD) in the general population could aid in identification and understanding of early disease processes. Metabolome measurements were performed on serum from 4742 individuals (2354 African-Americans and 1529 European-Americans from the Atherosclerosis Risk in Communities study and 859 Europeans from the Cooperative Health Research in the Region of Augsburg study). We examined 368 metabolites in relation to cross-sectional measures of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), their ratio (FEV1/FVC) and COPD using multivariable regression followed by meta-analysis. At a false discovery rate of 0.05, 95 metabolites were associated with FEV1 and 100 with FVC (73 overlapping), including inverse associations with branched-chain amino acids and positive associations with glutamine. Ten metabolites were associated with FEV1/FVC and seventeen with COPD (393 cases). Enriched pathways of amino acid metabolism were identified. Associations with FEV1 and FVC were not driven by individuals with COPD. We identified novel metabolic signatures of pulmonary function and COPD in African and European ancestry populations. These may allow development of biomarkers in the general population of early disease pathogenesis, before pulmonary function has decreased to levels diagnostic for COPD.

Ambient and controlled exposures to particulate air pollution and acute changes in heart rate variability and repolarization

Previous studies have reported increased risks of myocardial infarction in association with elevated ambient particulate matter (PM) in the previous hour(s). However, whether PM can trigger mechanisms that act on this time scale is still unclear. We hypothesized that increases in PM are associated with rapid changes in measures of heart rate variability and repolarization. We used data from panel studies in Augsburg, Germany, and Rochester, New York, USA, and two controlled human exposure studies in Rochester. Data included ECG recordings from all four studies, controlled exposures to (concentrated) ultrafine particles (UFP; particles with an aerodynamic diameter <100 nm) and ambient concentrations of UFP and fine PM (PM2.5, aerodynamic diameter <2.5 μm). Factor analysis identified three representative ECG parameters: standard deviation of NN-intervals (SDNN), root mean square of successive differences (RMSSD), and T-wave complexity. Associations between air pollutants and ECG parameters in the concurrent and previous six hours were estimated using additive mixed models adjusting for long- and short-term time trends, meteorology, and study visit number. We found decreases in SDNN in relation to increased exposures to UFP in the previous five hours in both of the panel studies (e.g. Augsburg study, lag 3 hours: −2.26%, 95% confidence interval [CI]: −3.98% to −0.53%; Rochester panel study, lag 1 hour: −2.69%; 95% CI: −5.13% to −0.26%) and one of the two controlled human exposure studies (1-hour lag: −13.22%; 95% CI: −24.11% to −2.33%). Similarly, we observed consistent decreases in SDNN and RMSSD in association with elevated PM2.5 concentrations in the preceding six hours in both panel studies. We did not find consistent associations between particle metrics and T-wave complexity. This study provided consistent evidence that recent exposures to UFP and PM2.5 can induce acute pathophysiological responses.

A network-based conditional genetic association analysis of the human metabolome.

BackgroundGenome-wide association studies have identified hundreds of loci that influence a wide variety of complex human traits; however, little is known regarding the biological mechanism of action of these loci. The recent accumulation of functional genomics (“omics”), including metabolomics data, has created new opportunities for studying the functional role of specific changes in the genome. Functional genomic data are characterized by their high dimensionality, the presence of (strong) statistical dependency between traits, and, potentially, complex genetic control. Therefore, the analysis of such data requires specific statistical genetics methods.ResultsTo facilitate our understanding of the genetic control of omics phenotypes, we propose a trait-centered, network-based conditional genetic association (cGAS) approach for identifying the direct effects of genetic variants on omics-based traits. For each trait of interest, we selected from a biological network a set of other traits to be used as covariates in the cGAS. The network can be reconstructed either from biological pathway databases (a mechanistic approach) or directly from the data, using a Gaussian graphical model applied to the metabolome (a data-driven approach). We derived mathematical expressions that allow comparison of the power of univariate analyses with conditional genetic association analyses. We then tested our approach using data from a population-based Cooperative Health Research in the region of Augsburg (KORA) study (n = 1,784 subjects, 1.7 million single-nucleotide polymorphisms) with measured data for 151 metabolites.ConclusionsWe found that compared to single-trait analysis, performing a genetic association analysis that includes biologically relevant covariates can either gain or lose power, depending on specific pleiotropic scenarios, for which we provide empirical examples. In the context of analyzed metabolomics data, the mechanistic network approach had more power compared to the data-driven approach. Nevertheless, we believe that our analysis shows that neither a prior-knowledge-only approach nor a phenotypic-data-only approach is optimal, and we discuss possibilities for improvement.

Prevalence and predictors of subclinical micronutrient deficiency in German older adults: Results from the population-based KORA-Age study

Introduction Subclinical micronutrient deficiency in older adults is associated with chronic age-related diseases and adverse functional outcomes. In Germany, the older population is at-risk of insufficient micronutrient intake, but representative studies on micronutrient status in old and very old adults are scarce. This study's objectives were to estimate the prevalence of subclinical vitamin D, folate, vitamin B12 and iron deficiencies among older adults, aged 65 to 93, from the KORA-Age study in Augsburg, Germany (n = 1079), and to examine associated predictors. Methods Serum concentrations of 25-hydroxyvitamin D (25OHD), folate, vitamin B12, and iron were analyzed and compared to selected cut-offs for subclinical micronutrient deficiency. Associated predictors were investigated using multiple logistic regression analysis. Results The prevalence of subclinical vitamin D and vitamin B12 deficiencies were high, with 52.0% and 27.3% of individuals having low 25OHD ( Conclusion Subclinical micronutrient deficiency is a public health concern among KORA-Age participants, especially for vitamins D and B12. The predictors identified provide further rationale for screening high-risk subgroups and developing targeted public health interventions to tackle prevailing micronutrient inadequacies among older adults.

Association of fetuin-A with incident type 2 diabetes: results from the MONICA/KORA Augsburg study and a systematic meta-analysis

We investigated the association of circulating fetuin-A with incident T2D particularly examining potential sex differences. Additionally, we determined whether putative associations were independent of subclinical inflammation, adiponectin and liver fat content. Case-cohort study plus systematic meta-analysis. We investigated the association between baseline fetuin-A levels and incident T2D in the MONICA/KORA Augsburg study using Cox proportional hazards analyses. Furthermore, we conducted a systematic review within PubMed and EMBASE and pooled association estimates of eligible studies with the MONICA/KORA Augsburg data using a DerSimonian-Laird random effects model. Within MONICA/KORA Augsburg, 930 participants developed incident T2D (median follow-up: 14 years). We observed a significant association between fetuin-A and T2D risk after multivariable adjustment including C-reactive protein and adiponectin. The strength of the association was similar in males and females (P value for sex interaction >0.55). Seven eligible published studies were identified in addition to the MONICA/KORA Augsburg study for the meta-analysis. The pooled hazard ratio (95% CI) for incident T2D per 1 standard deviation (s.d.) increment of fetuin-A was 1.24 (1.14-1.34) for the multivariable adjusted model. Our sex-stratified meta-analysis yielded relative risk estimates per 1 s.d. of 1.19 (1.04-1.38) in males and 1.29 (1.15-1.46) in females. Further individual adjustment for subclinical inflammation, adiponectin and liver fat content had almost no impact on the strength of the association. Higher fetuin-A levels are associated with incident T2D in both males and females independently of subclinical inflammation, adiponectin and liver fat content.

Long-term Air Pollution Exposure, Genome-wide DNA Methylation and Lung Function in the LifeLines Cohort Study.

Background:Long-term air pollution exposure is negatively associated with lung function, yet the mechanisms underlying this association are not fully clear. Differential DNA methylation may explain this association.Objectives:Our main aim was to study the association between long-term air pollution exposure and DNA methylation.Methods:We performed a genome-wide methylation study using robust linear regression models in 1,017 subjects from the LifeLines cohort study to analyze the association between exposure to nitrogen dioxide () and particulate matter (, fine particulate matter with aerodynamic diameter ; , particulate matter with aerodynamic diameter ) and , indicator of elemental carbon content (estimated with land-use-regression models) with DNA methylation in whole blood (Illumina® HumanMethylation450K BeadChip). Replication of the top hits was attempted in two independent samples from the population-based Cooperative Health Research in the Region of Augsburg studies (KORA).Results:Depending on the p-value threshold used, we found significant associations between exposure and DNA methylation for seven CpG sites (Bonferroni corrected threshold ) or for 4,980 CpG sites (False Discovery ). The top associated CpG site was annotated to the PSMB9 gene (i.e., cg04908668). None of the seven Bonferroni significant CpG-sites were significantly replicated in the two KORA-cohorts. No associations were found for PM exposure.Conclusions:Long-term exposure was genome-wide significantly associated with DNA methylation in the identification cohort but not in the replication cohort. Future studies are needed to further elucidate the potential mechanisms underlying –related respiratory disease. https://doi.org/10.1289/EHP2045

Prevalence and Predictors of Subclinical Micronutrient Deficiency in German Older Adults: Results from the Population-Based KORA-Age Study.

Subclinical micronutrient deficiency in older adults is associated with chronic age-related diseases and adverse functional outcomes. In Germany, the older population is at risk of insufficient micronutrient intake, but representative studies on micronutrient status in old and very old adults are scarce. This study’s objectives were to estimate the prevalence of subclinical vitamin D, folate, vitamin B12 and iron deficiencies among older adults, aged 65 to 93, from the KORA-Age study in Augsburg, Germany (n = 1079), and to examine associated predictors, using multiple logistic regression. Serum concentrations of 25-hydroxyvitamin D (25OHD), folate, vitamin B12, and iron were analyzed. The prevalence of subclinical vitamin D and vitamin B12 deficiencies were high, with 52.0% and 27.3% of individuals having low 25OHD (<50 nmol/L) and low vitamin B12 concentrations (<221 pmol/L), respectively. Furthermore, 11.0% had low iron (men <11.6 µmol/L, women <9.0 µmol/L) and 8.7% had low folate levels (<13.6 nmol/L). Common predictors associated with subclinical micronutrient deficiency included very old age, physical inactivity, frailty and no/irregular use of supplements. Subclinical micronutrient deficiency is a public health concern among KORA-Age participants, especially for vitamins D and B12. The predictors identified provide further rationale for screening high-risk subgroups and developing targeted public health interventions to tackle prevailing micronutrient inadequacies among older adults.

Metabolomic Profiling of Long-Term Weight Change: Role of Oxidative Stress and Urate Levels in Weight Gain.

ObjectiveTo investigate the association between long‐term weight change and blood metabolites.MethodsChange in BMI over 8.6 ± 3.79 years was assessed in 3,176 females from the TwinsUK cohort (age range: 18.3‐79.6, baseline BMI: 25.11 ± 4.35) measured for 280 metabolites at follow‐up. Statistically significant metabolites (adjusting for covariates) were included in a multivariable least absolute shrinkage and selection operator (LASSO) model. Findings were replicated in the Cooperative Health Research in the Region of Augsburg (KORA) study (n = 1,760; age range: 25‐70, baseline BMI: 27.72 ± 4.53). The study examined whether the metabolites identified could prospectively predict weight change in KORA and in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) study (n = 471; age range: 55‐74, baseline BMI: 27.24 ± 5.37).ResultsThirty metabolites were significantly associated with change in BMI per year in TwinsUK using Bonferroni correction. Four were independently associated with weight change in the multivariable LASSO model and replicated in KORA: namely, urate (meta‐analysis β [95% CI] = 0.05 [0.040 to 0.063]; P = 1.37 × 10−19), gamma‐glutamyl valine (β [95% CI] = 0.06 [0.046 to 0.070]; P = 1.23 × 10−20), butyrylcarnitine (β [95% CI] = 0.04 [0.028 to 0.051]; P = 6.72 × 10−12), and 3‐phenylpropionate (β [95% CI] = −0.03 [−0.041 to −0.019]; P = 9.8 × 10−8), all involved in oxidative stress. Higher levels of urate at baseline were associated with weight gain in KORA and PLCO.ConclusionsMetabolites linked to higher oxidative stress are associated with increased long‐term weight gain.

Hypertension in Germany.

Hypertension is a key risk factor. However, population data based on blood pressure measurements in Germany are scarce. Standardized blood pressure (BP) measurements and medication data from seven population-based studies conducted in Germany between 1994 and 2012 (66 845 participants, 25-74 years) were analyzed: the EPICPotsdam study (1994-1998, EPIC), the KORA-S4 Study (1999-2001) in Augsburg, and the Gutenberg Health Study (2007-2012, GHS) in Mainz/Mainz-Bingen provided data for descriptive comparisons. Time trends were analyzed based on identical study regions for the German National Health Interview and Examination Survey 1998 (BGS98) and the German Health Examination Survey for Adults (2008-11, DEGS1) as well as the Study of Health in Pomerania (SHIP) in Northeast Germany (1997-2001) and the SHIP-TREND study (2008-2012). BP data were adjusted for study-specific measurement devices based on calibration studies. After adjustment for study-specific measurement devices, mean systolic and diastolic BP values were lower and treatment proportions higher in recent (2007-2012) compared to older (1994-2001) studies. Mean BP decrease was most pronounced (systolic ≥ 10 mmHg) in the elderly (55-74 years). The regional SHIP-TREND data for Northeast Germany showed a decrease in mean systolic BP in young men aged 25 to 34 years; on a national level according to the DEGS1 data, however, no such decrease was observed for this group. New data add evidence for lower BP in Germany. However, the prevention potential remains high. Future research based on population-based data should place a special focus on blood pressure data in young men.

Does Citrulline Sit at the Nexus of Metformin's Pleotropic Effects on Metabolism and Mediate Its Salutatory Effects in Individuals With Type 2 Diabetes?

For more than two decades, physicians have prescribed metformin as the frontline pharmacological therapy to treat type 2 diabetes (T2D) despite knowing little about its underlying mechanisms of action (1). Metformin reduces hepatic glucose production (1) and has pleotropic effects on multiple tissues, including liver (1), muscle (2), and adipose (3) tissue, as well as on immune cells (4). Clinically, metformin also reduces the risk for cardiovascular diseases, cancers, and other diseases (5,6). Pharmacometabolomics provides an opportunity to measure changes in absolute and/or relative concentrations of hundreds to thousands of small molecules in biofluids and tissue extracts to determine the response and variations in response to therapy (7). Pharmacometabolomics could facilitate identification of metabolic pathways and mechanisms of action that contribute to metformin’s widespread salutatory effects (7). In this issue of Diabetes , Adam et al. (8) utilize this approach to “uncover” metformin’s effect on citrulline metabolism in individuals with and without T2D participating in the KORA (Cooperative Health Research in the Region of Augsburg) study. Adam et al. should be commended on conducting a thorough investigation of metformin’s impact on serum metabolites in individuals with T2D using nontargeted, semiquantitative liquid chromatography–tandem mass spectrometry coupled with rigorous statistical and bioinformatic analyses. The cross-sectional “human discovery” study revealed that out of a total of 353 identified serum metabolites, the concentrations of citrulline were significantly lower and X-21365 significantly higher in metformin-treated participants with T2D compared with nontreated participants. The longitudinal “human validation” study further demonstrated that the initiation of metformin treatment during the 7-year follow-up significantly reduced citrulline and increased X-21365 serum concentrations. Subsequently, the “translational” study showed that daily treatment with metformin in db/db diabetic mice decreased plasma, skeletal muscle, and epididymal …

Cost burden of type 2 diabetes in Germany: results from the population-based KORA studies

ObjectiveTo examine the impact of type 2 diabetes on direct and indirect costs and to describe the effect of relevant diabetes-related factors, such as type of treatment or glycaemic control...

Association of novel metrics of particulate matter with vascular markers of inflammation and coagulation in susceptible populations –results from a panel study

Background and aimsEpidemiological studies have shown adverse effects of ambient air pollutants on health with inflammation and oxidative stress playing an important role. We examine the association between blood biomarkers of inflammation and coagulation and physical attributes of particulate matter which are not routinely measured such as particle length or surface area concentration and apparent density of PM. MethodsBetween 3/2007 and 12/2008 187 non-smoking individuals with type 2 diabetes mellitus (T2D) or impaired glucose tolerance (IGT) were examined within the framework of the KORA Study in Augsburg, Germany. In addition, we selected 87 participants with a potential genetic predisposition on detoxifying and inflammatory pathways. This was defined by the null polymorphism for glutathione S-transferase M1 in combination with a certain single nucleotide polymorphism on the C-reactive protein (CRP) gene (rs1205) or the fibrinogen gene (rs1800790). Participants had blood drawn up to seven different times, resulting in 1765 blood samples. Air pollutants were collected at a central measurement station and individual 24-h averages calculated. Associations between air pollutants and high sensitivity CRP, myeloperoxidase (MPO), interleukin (IL)−6 and fibrinogen were analysed using additive mixed models. ResultsFor the panel with genetic susceptibility, increases were seen for CRP and MPO with most attributes, specifically particle length and active surface concentration. The %change of geometric mean and 95% confidence intervals for the 5-day average exposure for CRP and MPO were 34.6% [21.8;48.8] and 8.3% [3.2;13.6] per interquartile range increase of particle length concentration and 29.8% [15.9;45.3] and 10.4 [4.4;16.7] for active surface area. Results for the panel of T2D and IGT and the other blood biomarkers were less conclusive. ConclusionsParticle length concentration and active surface concentration showed strong positive associations with blood biomarkers reflecting inflammation. These air pollution metrics might reflect harmful aerosol properties better than particulate mass or number concentration. They might therefore be important for epidemiological studies.