Matthias Laudes

Christian-Albrechts-Universität zu Kiel, Kiel, Schleswig-Holstein, Germany

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Publications (69)209.19 Total impact

  • No preview · Article · Apr 2016 · Diabetologie und Stoffwechsel
  • No preview · Article · Apr 2016 · Diabetologie und Stoffwechsel
  • No preview · Article · Apr 2016 · Diabetologie und Stoffwechsel
  • No preview · Article · Apr 2016 · Diabetologie und Stoffwechsel
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    [Show abstract] [Hide abstract] ABSTRACT: Genome-wide association studies (GWAS) of chronic periodontitis (CP) defined by clinical criteria alone have had modest success to-date. Here, we refine the CP phenotype by supplementing clinical data with biological intermediates of microbial burden (levels of 8 periodontal pathogens) and local inflammatory response [gingival crevicular fluid (GCF) IL-1β] and derive periodontal complex traits (PCTs) via principal component analysis. PCTs were carried forward to GWAS (∼2.5 million markers) to identify PCT-associated loci among 975 European-American adult participants of the Dental ARIC study. We sought to validate these findings for CP in the larger ARIC cohort (n=821 participants with severe CP, 2031—moderate CP, 1914—healthy/mild disease) and an independent German sample including 717 aggressive periodontitis cases and 4210 controls. We identified 6 PCTs with distinct microbial community/IL-1β structures, albeit with overlapping clinical presentations. PCT1 was characterized by a uniformly high pathogen load, whereas PCT3 and PCT5 were dominated by A. actinomycetemcomitans and P. gingivalis, respectively. We detected genome-wide significant signals for PCT1 (CLEC19A, TRA, GGTA2P, TM9SF2, IFI16, RBMS3), PCT4 (HPVC1) and PCT5 (SLC15A4, PKP2, SNRPN). Overall, the highlighted loci included genes associated with immune response and epithelial barrier function. With the exception of associations of BEGAIN with severe and UBE3D with moderate CP, no other loci were associated with CP in ARIC or aggressive periodontitis in the German sample. Although not associated with current clinically-determined periodontal disease taxonomies, upon replication and mechanistic validation these candidate loci may highlight dysbiotic microbial community structures and altered inflammatory/immune responses underlying biological sub-types of CP.
    Full-text · Article · Mar 2016 · Human Molecular Genetics
  • [Show abstract] [Hide abstract] ABSTRACT: Atherosclerosis is a lipid-driven inflammatory disease, for which nanomedicinal interventions are under evaluation. Previously, we showed that liposomal nanoparticles loaded with prednisolone (LN-PLP) accumulated in plaque macrophages, however, induced proatherogenic effects in patients. Here, we confirmed in low-density lipoprotein receptor knockout (LDLr(-/-)) mice that LN-PLP accumulates in plaque macrophages. Next, we found that LN-PLP infusions at 10mg/kg for 2 weeks enhanced monocyte recruitment to plaques. In follow up, after 6 weeks of LN-PLP exposure we observed (i) increased macrophage content, (ii) more advanced plaque stages, and (iii) larger necrotic core sizes. Finally, in vitro studies showed that macrophages become lipotoxic after LN-PLP exposure, exemplified by enhanced lipid loading, ER stress and apoptosis. These findings indicate that liposomal prednisolone may paradoxically accelerate atherosclerosis by promoting macrophage lipotoxicity. Hence, future (nanomedicinal) drug development studies are challenged by the multifactorial nature of atherosclerotic inflammation.
    No preview · Article · Mar 2016 · Nanomedicine: nanotechnology, biology, and medicine
  • [Show abstract] [Hide abstract] ABSTRACT: In the present study the relationship between the CoQ10 redox state (% oxidized form of CoQ10 ) and the serum level of c-reactive protein (CRP) was investigated in a large Caucasian study population (n = 1319). In order to evaluate independently the influence of the variables that predict the outcome of CRP, an analysis of covariance (ANCOVA) was performed with CRP as the dependent variable. Gender was taken as an independent factor and CoQ10 redox and BMI as independent covariates. Results were substantiated with findings from a human intervention study (n = 53), receiving 150 mg/day ubiquinol for 14 days. Spearman's correlation revealed a significant (P < 0.001) association between the CoQ10 redox state and CRP concentrations in the whole study population. Thus, higher CRP concentrations were found in subjects having more oxidized CoQ10 . Similar results were evident for further inflammatory markers (interleukin-6, number of leucocytes). The ANCOVA revealed a significant (P < 0.001) prediction of CRP concentrations by CoQ10 redox state, after controlling for the effect of BMI and separately for gender. In the intervention study it was further found that the oral intake of ubiquinol increased its proportion significantly (P < 0.001), with the highest increase in those persons having a low basal serum ubiquinol content (<92.3%). Here it was discovered that the ubiquinol status significantly correlated to the concentration of the inflammation marker monocyte chemotactic protein 1. It is concluded that CoQ10 redox state predicts the concentration of CRP. Persons at risk with lower ubiquinol status, higher BMI, and low grade inflammation may benefit from ubiquinol supplementation. © 2016 BioFactors, 2016.
    No preview · Article · Feb 2016 · BioFactors
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    [Show abstract] [Hide abstract] ABSTRACT: Coenzyme Q10 (CoQ10) is synthesized in almost all human tissues and presumably involved in age-related alterations and diseases. Here, we examined the impact of aging and sex on the serum CoQ10 status in 860 European adults ranging in age from 18 to 82 years. We identified an inverse U-shaped relationship between CoQ10 concentration and age. Women showed lower cholesterol-adjusted CoQ10 levels than men, irrespective of age. As observed in both sexes, the decrease in CoQ10 concentration in older subjects was accompanied by a shift in the redox status in favour of the oxidized form. A strong positive correlation was found for total CoQ10 and cholesterol concentrations (Spearman’s, p≤1E-74). We found strong negative correlations between total (Spearman’s, p≤1E-07) and between cholesterol-adjusted CoQ10 concentration (Spearman’s, p≤1E-14) and the proportion of the oxidized form of CoQ10. These correlations were not dependent on age and sex and were attenuated by supplementation with 150 mg/day reduced CoQ10 for 14 days. Overall, our results are useful to define risk groups with critical CoQ10 status in humans. In particular, older subjects were characterized by impaired CoQ10 status due to their lowered serum CoQ10 concentration and concomitant decrease of CoQ10 redox capacity.
    Preview · Article · Jan 2016 · Journal of Clinical Biochemistry and Nutrition
  • [Show abstract] [Hide abstract] ABSTRACT: Coenzyme Q10 (CoQ10 ) exists in a reduced (ubiquinol) and an oxidized (ubiquinone) form in all human tissues and functions, amongst others, in the respiratory chain, redox-cycles, and gene expression. As the status of CoQ10 is an important risk factor for several diseases, here we determined the CoQ10 status (ubiquinol, ubiquinone) in a large Caucasian study population (n = 1,911). The study population covers a wide age range (age: 18-83 years, 43.4% men), has information available on more than 10 measured clinical phenotypes, more than 30 diseases (presence vs. absence), about 30 biomarkers, and comprehensive genetic information including whole-genome SNP typing (>891,000 SNPs). The major aim of this long-term resource in CoQ10 research is the comprehensive analysis of the CoQ10 status with respect to integrated health parameters (i.e., fat metabolism, inflammation), disease-related biomarkers (i.e., liver enzymes, marker for heart failure), common diseases (i.e., neuropathy, myocardial infarction), and genetic risk in humans. Based on disease status, biomarkers, and genetic variants, our cohort is also useful to perform Mendelian randomisation approaches. In conclusion, the present study population is a promising resource to gain deeper insight into CoQ10 status in human health and disease. © 2015 BioFactors, 2015. © 2015 International Union of Biochemistry and Molecular Biology.
    No preview · Article · Jul 2015 · BioFactors
  • [Show abstract] [Hide abstract] ABSTRACT: Obesity is associated with low-grade systemic inflammation which is thought to trigger the development of comorbidities such as type 2 diabetes. The soluble receptor for advanced glycation end products (sRAGE) belongs to the innate immune system and has been linked to obesity, recently. The aim of the present study was to examine whether serum sRAGE concentrations are related to the grade of weight loss and improvement of insulin resistance due to a very low calorie diet (VLCD). 22 severe obese subjects (Median Body Mass Index (BMI): 44.5kg/m(2)) were included in a dietary intervention study of 6month, consisting of a very low calorie formula diet phase (VLCD: 800kcal/d) for 12weeks and a following 12week weight maintenance phase. Fasting glucose, fasting insulin, adiponectin, leptin and sRAGE were determined from sera. Insulin sensitivity was estimated by Homeostasis Model Assessment (HOMA) index and leptin-to-adiponectin-ratio (LAR). Mean body weight reduction by VLCD accounted to 21.7kg with a significant improvement of insulin resistance. At baseline, sRAGE serum levels were significantly inversely related to BMI (rS=-0.642, p=0.001) and HOMA (rS=-0.419, p=0.041). Of interest, sRAGE serum levels at baseline were significantly lower in study subjects with greater reduction of BMI (p=0.017). In addition, a significantly greater HOMA reduction was observed in subjects with lower sRAGE serum levels at baseline (p=0.006). Finally, correlation analysis revealed, that changes of sRAGE serum levels were significantly correlated to changes of BMI (rS=-0.650, p=0.022) during intervention. Anti-inflammatory sRAGE might be a potential future biomarker to predict weight loss and improvement of insulin resistance by a VLCD whereby lower baseline sRAGE serum levels indicate a better outcome of the dietary intervention. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Mar 2015 · Cytokine
  • No preview · Article · Mar 2015 · Experimental and Clinical Endocrinology & Diabetes
  • [Show abstract] [Hide abstract] ABSTRACT: In prior studies, lifestyle indices were associated with numerous disease end points, but the association with fatty liver disease (FLD), a key correlate of cardiometabolic risk, is unknown. The aim was to investigate associations between a lifestyle index with liver fat content. Liver fat was quantified by MRI as liver signal intensity (LSI) in 354 individuals selected from a population-based cohort from Germany. Exposure to favourable lifestyle factors was quantified using an additive score with each factor modelled as a dichotomous trait. Favourable lifestyle factors were defined as waist circumference below 102 (men) or 88 cm (women), physical activity ≥3.5 h/week, never-smoking and a favourable dietary pattern, which was derived to explain liver fat variation. In a cross-sectional study, multivariable adjusted linear and logistic regression was applied to investigate the association between the lifestyle index (range 0-4, exposure) and LSI (modelled as a continuous trait or dichotomised as a FLD indicator variable, respectively). Individuals with four favourable lifestyle factors (n=9%) had lower LSI values (ß -0.40; 95% CI -0.61 to -0.19) and a lower OR (0.09; 95% CI 0.03 to 0.30) for FLD compared with individuals with zero favourable lifestyle factors (n=10%). A healthy lifestyle pattern was associated with less liver fat. Prospective studies are warranted. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    No preview · Article · Mar 2015 · Journal of Epidemiology & Community Health
  • D M Schulte · N Cupa · M Ahrens · M Laudes
    [Show abstract] [Hide abstract] ABSTRACT: A 50-year-old Caucasian woman was admitted to our hospital with intermittent diarrhoea, emesis and increasingly brown-coloured skin, mainly the in light-exposed areas, after biliopancreatic diversion for obesity treatment. Differential diagnoses such as adrenal insufficiency were ruled out, but biochemical analysis demonstrated unusual high pyridoxine serum levels (vitamin B6). History revealed the intake of 300 mg of vitamin B6 per day over 6 months as described by her general practitioner. All symptoms disappeared after the discontinuation of vitamin B6 supplementation. Importantly, in contrast to many other vitamins and supplements, there is no evidence in the literature of the occurrence of vitamin B6 deficiency after bariatric surgery. Therefore, supplementation of vitamins and supplements in bariatric patients has to be carefully considered according to the existing clinical guidelines, as uncritical oversupplementation of micronutrients might result in intoxication and serious illness as presented here.European Journal of Clinical Nutrition advance online publication, 3 June 2015; doi:10.1038/ejcn.2015.83.
    No preview · Article · Mar 2015 · Experimental and Clinical Endocrinology & Diabetes
  • [Show abstract] [Hide abstract] ABSTRACT: Lipoprotein(a) [Lp(a)] is a highly atherogenic lipid particle. While earlier reports suggested Lp(a) levels mostly being determined by genetic factors, several recent studies revealed Lp(a) induction also to be caused by chronic inflammation. Therefore, we aimed to examine whether cytokine blockade by monoclonal antibodies may inhibit Lp(a) metabolism. We found that IL-6 blockade by tocilizumab (TCZ) reduced Lp(a) while TNF-α-inhibition by adalimumab in humans had no effect. The specificity of IL-6 in regulating Lp(a) was further demonstrated by serological measurements of n=1153 human subjects revealing that Lp(a) levels are increased in individuals with elevated serum IL-6. Transcriptomic analysis of n=57 human liver biopsies revealed typical IL-6 response genes being correlated with the LPA gene expression in vivo. On a molecular level, we found that TCZ inhibited IL-6-induced LPA mRNA and protein expression in human hepatocytes. Furthermore, examination of IL-6-responsive STAT3-binding sites within the LPA promoter by reporter gene assays, promoter deletion experiments and EMSA analysis showed that the Lp(a) lowering effect of TCZ is specifically mediated via a responsive element at -46 to -40. Therefore, IL-6 blockade might be a potential therapeutic option to treat elevated Lp(a) serum concentrations in humans and therefore might be a non-invasive alternative to lipid apheresis in the future. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
    No preview · Article · Feb 2015 · The Journal of Lipid Research
  • [Show abstract] [Hide abstract] ABSTRACT: After his study of food science at the Rheinische Friedrich-Wilhelms University of Bonn, Tobias J Demetrowitsch obtained his doctoral degree in the research field of metabolomics at the Christian-Albrechts-University of Kiel. The present paper is part of his doctoral thesis and describes an extended strategy to evaluate and verify complex or large-scale experiments and data sets. Large-scale studies result in high sample numbers, requiring the analysis of samples in different batches. So far, the verification of such LC-MS-based metabolomics studies is difficult. Common approaches have not provided a reliable validation procedure to date. This article shows a novel verification process for a large-scale human urine study (analyzed by a LC/QToF-MS system) using a two-step validation procedure. The first step comprises a targeted approach that aims to examine and exclude statistical outliers. The second step consists of a principle component analysis, with the aim of a tight cluster of all quality controls and a second for all volunteer samples. The applied study design provides a reliable two-step validation procedure for large-scale studies and additionally contains an inhouse verification procedure.
    No preview · Article · Jan 2015 · Bioanalysis
  • [Show abstract] [Hide abstract] ABSTRACT: Sepsis and type 2 diabetes exhibit insulin resistance as a common phenotype. In type 2 diabetes we and others have recently provided evidence that alterations of the pro-inflammatory wnt5a/anti-inflammatory sFRP5 system are involved in the pathogenesis of insulin resistance. The aim of the present study was to investigate whether this novel cytokine system is dysregulated in human sepsis which may indicate a potential mechanism linking inflammation to metabolism.In this single-centre prospective observational study, critically ill adult septic patients were examined and pro-inflammatory wnt5a and wnt5a inhibitor sFRP5 were measured in serum samples by ELISA at admission to the intensive care unit (ICU) and 5 days later. 60 sepsis patients were included and 30 healthy individuals served as controls.Wnt5a levels were found to be significantly increased in septic patients compared to healthy controls (2.21±0.33 ng/ml vs. 0.32±0.03 ng/ml, p<0.0001). In contrast, sFRP5 was not significantly altered in septic patients (19.72±3.06 ng/ml vs. 17.48±6.38 ng/ml, p=0.07). On admission to the ICU, wnt5a levels exhibited a significant positive correlation with the leukocyte count (rs=0.3797, p=0.004). Interestingly, in patients recovering from sepsis, wnt5a levels significantly declined within 5 days (2.17±0.38 ng/ml to 1.03±0.28 ng/ml, p<0.01). In contrast, if sepsis was worsening, wnt5a levels increased in the same time period by trend (2.34±0.59 ng/ml to 3.25±1.02 ng/ml, p>0.05). sFRP5 levels did not significantly change throughout the study period.The wnt5a/sFRP5 system is altered in human sepsis and might therefore be of interest for future studies on molecular pathophysiology of this common human disease.
    No preview · Article · Nov 2014 · Clinical & Experimental Immunology
  • [Show abstract] [Hide abstract] ABSTRACT: Diet is related to many chronic disease conditions such as the metabolic syndrome (MetS). We set out to compare behaviour-related with disease-related patterns and their association with the MetS in a German cross-sectional study. A total of 905 participants of a Northern German cohort (aged 25-82 years) completed a FFQ, underwent anthropometric assessments and provided a blood sample. Dietary patterns were derived by principal component analysis (PCA) and reduced-rank regression (RRR) from forty-two food groups. Components of the MetS were used as response variables for the RRR analysis. Simplified patterns comprising ten food groups were generated. Logistic regression analysis was performed to evaluate the likelihood of having the MetS across the quartiles of simplified pattern scores. We identified two similar dietary patterns derived by PCA and RRR characterised by high intakes of potatoes, various vegetables, red and processed meat, fats, sauce and bouillon. Comparing simplified patterns, an increased RRR pattern score was associated with a higher OR (2·18, 95 % CI 1·25, 3·81) of having the MetS than an increased PCA pattern score (OR 1·92, 95 % CI 1·21, 3·03). Comparing concordant food groups by both dietary pattern methods, a diet high in legumes, beef, processed meat and bouillon was also positively associated with the prevalence of the MetS after adjustment for potential confounders (OR 1·71, 95 % CI 1·04, 2·79). We identified a behaviour-related pattern that was positively associated with the MetS. The application of both dietary pattern methods may be advantageous to obtain information for designing and realising dietary guidelines. Prospective studies are needed to confirm the results.
    No preview · Article · Oct 2014 · British Journal Of Nutrition
  • No preview · Article · May 2014 · Diabetologie und Stoffwechsel
  • No preview · Article · May 2014 · Diabetologie und Stoffwechsel
  • N Müller · C Saggau · DM Schulte · M Laudes
    No preview · Article · May 2014 · Diabetologie und Stoffwechsel

Publication Stats

923 Citations
209.19 Total Impact Points

Institutions

  • 2012-2014
    • Christian-Albrechts-Universität zu Kiel
      • Institute of Experimental Medicine
      Kiel, Schleswig-Holstein, Germany
  • 2001-2010
    • University of Cologne
      • • Department of Internal Medicine
      • • Interdisciplinary Postgraduate Program in Molecular Medicine
      • • Division of Cardiology, Pneumology, Angiology and Intensive Care
      Köln, North Rhine-Westphalia, Germany
  • 2004-2006
    • University of Cambridge
      • Department of Clinical Biochemistry
      Cambridge, England, United Kingdom