Matthias Laudes

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

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Publications (59)186.28 Total impact

  • [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.
    BioFactors 07/2015; DOI:10.1002/biof.1216 · 3.00 Impact Factor
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    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.
    Cytokine 03/2015; 73(2):265-269. DOI:10.1016/j.cyto.2015.02.022 · 2.87 Impact Factor
  • Experimental and Clinical Endocrinology & Diabetes 03/2015; 122(03). DOI:10.1055/s-0035-1547693 · 1.76 Impact Factor
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    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.
    Journal of Epidemiology &amp Community Health 03/2015; 69(8). DOI:10.1136/jech-2014-204989 · 3.29 Impact Factor
  • D M Schulte · N Cupa · M Ahrens · M Laudes
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    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.
    Experimental and Clinical Endocrinology & Diabetes 03/2015; 122(03). DOI:10.1055/s-0035-1547622 · 1.76 Impact Factor
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    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.
    The Journal of Lipid Research 02/2015; 56(5). DOI:10.1194/jlr.P052209 · 4.73 Impact Factor
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    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.
    Bioanalysis 01/2015; 7(1):103-12. DOI:10.4155/bio.14.270 · 3.03 Impact Factor
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    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.
    Clinical & Experimental Immunology 11/2014; 180(1). DOI:10.1111/cei.12484 · 3.28 Impact Factor
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    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.
    British Journal Of Nutrition 10/2014; 112(8):1364-1372. DOI:10.1017/S0007114514002098 · 3.34 Impact Factor
  • Diabetologie und Stoffwechsel 05/2014; 9(S 01). DOI:10.1055/s-0034-1375035 · 0.31 Impact Factor
  • N Müller · C Saggau · DM Schulte · M Laudes
    Diabetologie und Stoffwechsel 05/2014; 9(S 01). DOI:10.1055/s-0034-1374886 · 0.31 Impact Factor
  • Diabetologie und Stoffwechsel 05/2014; 9(S 01). DOI:10.1055/s-0034-1375039 · 0.31 Impact Factor
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    ABSTRACT: Psoriasis is associated with comorbidity including obesity, insulin resistance and diabetes mellitus type 2. In obesity the protein wnt5a is released from adipose tissue macrophages and was shown to be of importance in the development of insulin resistance. As wnt5a was also shown to be up-regulated in psoriatic skin lesions we investigated if wnt5a and its counterpart sFRP5 are altered in the circulation of lean and obese patients with psoriasis compared to lean and obese healthy volunteers by measuring serum concentrations of both proteins. Our results showed that wnt5a was significantly higher in lean patients with psoriasis (0.096 ng/ml; SD 0.12) compared to lean healthy controls (0.020 ng/ml; SD 0.04; p=<0.01) as well as in obese patients (0.177 ng/ml; SD 0.14) compared to obese healthy controls (0.011 ng/ml; SD 0.03; p=<0.001). Therefore, we suggest that in psoriasis an increase of wnt5a may contribute to the development of metabolic comorbidity. This article is protected by copyright. All rights reserved.
    Experimental Dermatology 04/2014; 23(6). DOI:10.1111/exd.12413 · 4.12 Impact Factor
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    ABSTRACT: Inflammation and metabolism have been shown to be evolutionary linked and increasing evidence exists that pro-inflammatory factors are involved in the pathogenesis of obesity and type 2 diabetes. Until now, most data suggest that within adipose tissue these factors are secreted by cells of the innate immune system, e. g. macrophages. In the present study we demonstrate that B lymphocyte stimulator (BLyS) is increased in human obesity. In contrast to several pro-inflammatory factors, we found the source of BLyS in human adipose tissue to be the adipocytes rather than immune cells. In grade 3 obese human subjects, expression of BLyS in vivo in adipose tissue is significantly increased (p<0.001). Furthermore, BLyS serum levels are elevated in grade 3 human obesity (862.5+222.0 pg/ml vs. 543.7+60.7 pg/ml in lean controls, p<0.001) and are positively correlated to the BMI (r = 0.43, p<0.0002). In the present study, bariatric surgery significantly altered serum BLyS concentrations. In contrast, weight loss due to a very-low-calorie-formula-diet (800 kcal/d) had no such effect. To examine metabolic activity of BLyS, in a translational research approach, insulin sensitivity was measured in human subjects in vivo before and after treatment with the human recombinant anti-BLyS antibody belimumab. Since BLyS is known to promote B-cell proliferation and immunoglobulin secretion, the present data suggest that adipocytes of grade 3 obese human subjects are able to activate the adaptive immune system, suggesting that in metabolic inflammation in humans both, innate and adaptive immunity, are of pathophysiological relevance.
    PLoS ONE 04/2014; 9(4):e94282. DOI:10.1371/journal.pone.0094282 · 3.23 Impact Factor
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    ABSTRACT: lincRNAs recently have been discovered as evolutionary conserved transcripts of non-coding DNA sequences and have been implicated in the regulation of cellular differentiation. In humans, molecular studies have suggested a functional role for lincRNAs in cancer development. The aim of the present study was to examine whether these novel molecules are specifically regulated by different cytokines in cells of the innate immune system in humans in vivo and whether lincRNAs thereby might be involved in the pathophysiology of rheumatoid arthritis (RA). Therefore, CD14(+) monocytes were isolated from RA patients before and after anti-IL-6R (tocilizumab) or anti-TNF-α (adalimumab) therapy and lincRNA transcription was analysed by a microarray based experiment. As expected, we found lincRNAs to be present in CD14(+) monocytes of RA patients. However, of the total number of 7.419 lincRNAs examined in this study only a very small number was significantly regulated by either IL-6 or TNF-α (85 lincRNAs, corresponding to 1.1%). The numbers of lincRNAs regulated was higher due to TNF-α compared to IL-6. Interestingly, none of the identified lincRNAs was influenced by both, IL-6 and TNF-α, suggesting the regulation of lincRNA transcription to be highly specific for distinct cytokines. Taken together, our results suggest (1) that lincRNAs are novel intracellular molecular effectors of specific cytokines in cells of the innate immune system in humans in vivo and (2) that lincRNAs might be involved in the molecular pathophysiology of RA.
    Cytokine 04/2014; 68(1). DOI:10.1016/j.cyto.2014.03.004 · 2.87 Impact Factor
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    ABSTRACT: The aim of the present study was to examine to what extent different social network mechanisms are involved in the pathogenesis of obesity and insulin-resistance. We used nonparametric and parametric regression models to analyse whether individual BMI and HOMA-IR are determined by social network characteristics. A total of 677 probands (EGO) and 3033 social network partners (ALTER) were included in the study. Data gathered from the probands include anthropometric measures, HOMA-IR index, health attitudes, behavioural and socio-economic variables and social network data. We found significant treatment effects for ALTERs frequent dieting (p<0.001) and ALTERs health oriented nutritional attitudes (p<0.001) on EGO's BMI, establishing a significant indirect network effect also on EGO's insulin resistance. Most importantly, we also found significant direct social network effects on EGO's insulin resistance, evidenced by an effect of ALTERs frequent dieting (p = 0.033) and ALTERs sport activities (p = 0.041) to decrease EGO's HOMA-IR index independently of EGO's BMI. Social network phenomena appear not only to be relevant for the spread of obesity, but also for the spread of insulin resistance as the basis for type 2 diabetes. Attitudes and behaviour of peer groups influence EGO's health status not only via social mechanisms, but also via socio-biological mechanisms, i.e. higher brain areas might be influenced not only by biological signals from the own organism, but also by behaviour and knowledge from different human individuals. Our approach allows the identification of peer group influence controlling for potential homophily even when using cross-sectional observational data.
    PLoS ONE 04/2014; 9(4):e93860. DOI:10.1371/journal.pone.0093860 · 3.23 Impact Factor
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    ABSTRACT: This case report describes two female lupus patients who both received biological treatment with tocilizumab and with belimumab. The disease course was remarkably similar in both cases. Tocilizumab resulted in a transient improvement in pleurisy and arthritis but was then followed by a clinical flare accompanied by an increase in autoantibodies and a drop in complement levels. Alike, both patients experienced a rapid and sustained improvement after institution of belimumab. The clinical benefit obtained is currently stable under ongoing belimumab therapy.
    Lupus 01/2014; 23(4). DOI:10.1177/0961203314520844 · 2.48 Impact Factor
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    ABSTRACT: lincRNAs recently have been discovered as evolutionary conserved transcripts of non-coding DNA sequences and have been implicated in the regulation of cellular differentiation. In humans, molecular studies have suggested a functional role for lincRNAs in cancer development. The aim of the present study was to examine whether these novel molecules are specifically regulated by different cytokines in cells of the innate immune system in humans in vivo and whether lincRNAs thereby might be involved in the pathophysiology of rheumatoid arthritis (RA). Therefore, CD14+ monocytes were isolated from RA patients before and after anti-IL-6R (tocilizumab) or anti-TNF-α (adalimumab) therapy and lincRNA transcription was analysed by a microarray based experiment. As expected, we found lincRNAs to be present in CD14+ monocytes of RA patients. However, of the total number of 7.419 lincRNAs examined in this study only a very small number was significantly regulated by either IL-6 or TNF-α (85 lincRNAs, corresponding to 1.1%). The numbers of lincRNAs regulated was higher due to TNF-α compared to IL-6. Interestingly, none of the identified lincRNAs was influenced by both, IL-6 and TNF-α, suggesting the regulation of lincRNA transcription to be highly specific for distinct cytokines. Taken together, our results suggest (1) that lincRNAs are novel intracellular molecular effectors of specific cytokines in cells of the innate immune system in humans in vivo and (2) that lincRNAs might be involved in the molecular pathophysiology of RA.
    Cytokine 01/2014; · 2.87 Impact Factor
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    ABSTRACT: The concentration of serum testosterone is mainly regulated by the testicular function, which is under control of the central hypothalamic-pituitary-gonadal axis. A certain amount of testosterone is converted into β-estradiol by adipose tissue. Obesity in men is often associated with decreased androgen levels. The aim of the present study was to examine the effect of caloric restriction on serum testosterone levels in obese men. Dietary intervention study was performed with a very low calorie diet (800 kcal/d) for 12 weeks. Thirteen obese human male subjects (median body mass index: 42.7 kg/m2) were included. Body composition was assessed by impedance analysis. Insulin sensitivity was estimated by leptin-to-adiponectin ratio (LAR). Testosterone (T), β-estradiol, albumin, sex hormone-binding globulin (SHBG), LH, and FSH serum concentrations were measured by enzyme immunoassays. Statistical analysis was performed on baseline and values after 3 months. Caloric restriction significantly increased total testosterone (6.97 nmol/l to 13.21 nmol/l; p=0.001) and SHBG (22.11 nmol/l to 42.12 nmol/l; p=0.001) concentrations in serum. This is caused by a significant improvement of the testicular function (LH/T: 0.36-0.20; p=0.005) and a significant reduction of the T/β-estradiol conversion rate (73.59-104.29; p=0.003). There was a significant negative correlation of improvement of testicular function and LAR (rs=-0.683 (p=0.042)). In obese men caloric restriction significantly increases the serum testosterone concentration. This is achieved by 2 distinct mechanisms, that is, improvement of testicular function and reduced conversion of testosterone to β-estradiol by aromatase activity of the adipose tissue.
    Hormone and Metabolic Research 11/2013; 46(4). DOI:10.1055/s-0033-1358678 · 2.04 Impact Factor
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    ABSTRACT: OBJECTIVES: Blocking the interleukin-6 pathway by tocilizumab (TCZ) has been associated with changes in the lipoprotein profile, which could adversely impact cardiovascular (CV) risk in patients with rheumatoid arthritis (RA). In the present study, we addressed the effect of TCZ on lipoproteins in both fasting and non-fasting state in RA patients and tested the effect of TCZ on LDL receptor (LDLr) expression in vitro. METHODS: Twenty patients with active RA and an inadequate response to TNF blockers received monthly TCZ intravenously. On week 0, 1 and 6 blood was drawn before and after an oral fat load, the lipid profiles and HDL antioxidative capacity were measured. Effects of TCZ on LDLr expression in transfected HepG2 cells were subjected. RESULTS: After 6 weeks of TCZ, total cholesterol increased by 22% (4.8 ± 0.9 to 5.9 ± 1.3 mmol/L; p < 0.001), LDLc by 22% (3.0 ± 0.6 to 3.6 ± 0.8 mmol/L; p < 0.001) and HDLc by 17% (1.4 ± 0.4 to 1.7 ± 0.7 mmol/L; p < 0.016). Fasting triglycerides (TG) increased by 48% (1.0 ± 0.4 to 1.4 ± 0.8 mmol/L; p = 0.011), whereas postprandial incremental area under the curve TG increased by 62% (p = 0.002). Lipid changes were unrelated to the change in disease activity or inflammatory markers. No difference in HDL antioxidative capacity was found. In vitro, LDLr expression in cultured liver cells was significantly decreased following TCZ incubation (P < 0.001). CONCLUSIONS: TCZ adversely impacts on both LDLc as well as fasting and postprandial TG in patients with RA. The changes in hepatic LDLr expression following TCZ imply that adverse lipid changes may be a direct hepatic effect of TCZ. The net effect of TCZ on CV-morbidity has to be confirmed in future clinical trials.
    Atherosclerosis 05/2013; 229(1). DOI:10.1016/j.atherosclerosis.2013.04.031 · 3.97 Impact Factor

Publication Stats

761 Citations
186.28 Total Impact Points

Institutions

  • 2012–2015
    • Christian-Albrechts-Universität zu Kiel
      • Institute of Experimental Medicine
      Kiel, Schleswig-Holstein, Germany
  • 2012–2014
    • University Medical Center Schleswig-Holstein
      Kiel, Schleswig-Holstein, Germany
  • 2008–2012
    • University of Cologne
      • Department of Internal Medicine
      Köln, North Rhine-Westphalia, Germany
  • 2004–2010
    • University of Cambridge
      • • Department of Clinical Biochemistry
      • • Department of Biochemistry
      Cambridge, ENG, United Kingdom