29 results on '"Kootte RS"'
Search Results
2. Novel Proteome Targets Marking Insulin Resistance in Metabolic Syndrome.
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Warmbrunn MV, Bahrar H, de Clercq NC, Koopen AM, de Groot PF, Rutten J, Joosten LAB, Kootte RS, Bouter KEC, Ter Horst KW, Hartstra AV, Serlie MJ, Soeters MR, van Raalte DH, Davids M, Levin E, Herrema H, Riksen NP, Netea MG, Groen AK, and Nieuwdorp M
- Subjects
- Humans, Male, Female, Cross-Sectional Studies, Middle Aged, Adult, Glucose Clamp Technique, Obesity metabolism, Adipose Tissue metabolism, Insulin blood, Insulin metabolism, Intra-Abdominal Fat metabolism, Insulin Resistance, Metabolic Syndrome metabolism, Biomarkers blood, Proteome
- Abstract
Context/objective: In order to better understand which metabolic differences are related to insulin resistance in metabolic syndrome (MetSyn), we used hyperinsulinemic-euglycemic (HE) clamps in individuals with MetSyn and related peripheral insulin resistance to circulating biomarkers., Design/methods: In this cross-sectional study, HE-clamps were performed in treatment-naive men (n = 97) with MetSyn. Subjects were defined as insulin-resistant based on the rate of disappearance (Rd). Machine learning models and conventional statistics were used to identify biomarkers of insulin resistance. Findings were replicated in a cohort with n = 282 obese men and women with (n = 156) and without (n = 126) MetSyn. In addition to this, the relation between biomarkers and adipose tissue was assessed by nuclear magnetic resonance imaging., Results: Peripheral insulin resistance is marked by changes in proteins related to inflammatory processes such as IL-1 and TNF-receptor and superfamily members. These proteins can distinguish between insulin-resistant and insulin-sensitive individuals (AUC = 0.72 ± 0.10) with MetSyn. These proteins were also associated with IFG, liver fat (rho 0.36, p = 1.79 × 10
-9 ) and visceral adipose tissue (rho = 0.35, p = 6.80 × 10-9 ). Interestingly, these proteins had the strongest association in the MetSyn subgroup compared to individuals without MetSyn., Conclusions: MetSyn associated with insulin resistance is characterized by protein changes related to body fat content, insulin signaling and pro-inflammatory processes. These findings provide novel targets for intervention studies and should be the focus of future in vitro and in vivo studies.- Published
- 2024
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3. Overweight and Obesity Are Associated With Acute Kidney Injury and Acute Respiratory Distress Syndrome, but Not With Increased Mortality in Hospitalized COVID-19 Patients: A Retrospective Cohort Study.
- Author
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van Son J, Oussaada SM, Şekercan A, Beudel M, Dongelmans DA, van Assen S, Eland IA, Moeniralam HS, Dormans TPJ, van Kalkeren CAJ, Douma RA, Rusch D, Simsek S, Liu L, Kootte RS, Wyers CE, IJzerman RG, van den Bergh JP, Stehouwer CDA, Nieuwdorp M, Ter Horst KW, and Serlie MJ
- Subjects
- Aged, Female, Humans, Intensive Care Units, Length of Stay, Male, Middle Aged, Patient Discharge, Respiration, Artificial, Retrospective Studies, Treatment Outcome, Acute Kidney Injury complications, COVID-19 mortality, Hospital Mortality, Hospitalization, Obesity complications, Respiratory Distress Syndrome complications
- Abstract
Objective: To evaluate the association between overweight and obesity on the clinical course and outcomes in patients hospitalized with COVID-19., Design: Retrospective, observational cohort study., Methods: We performed a multicenter, retrospective, observational cohort study of hospitalized COVID-19 patients to evaluate the associations between overweight and obesity on the clinical course and outcomes., Results: Out of 1634 hospitalized COVID-19 patients, 473 (28.9%) had normal weight, 669 (40.9%) were overweight, and 492 (30.1%) were obese. Patients who were overweight or had obesity were younger, and there were more women in the obese group. Normal-weight patients more often had pre-existing conditions such as malignancy, or were organ recipients. During admission, patients who were overweight or had obesity had an increased probability of acute respiratory distress syndrome [OR 1.70 (1.26-2.30) and 1.40 (1.01-1.96)], respectively and acute kidney failure [OR 2.29 (1.28-3.76) and 1.92 (1.06-3.48)], respectively. Length of hospital stay was similar between groups. The overall in-hospital mortality rate was 27.7%, and multivariate logistic regression analyses showed that overweight and obesity were not associated with increased mortality compared to normal-weight patients., Conclusion: In this study, overweight and obesity were associated with acute respiratory distress syndrome and acute kidney injury, but not with in-hospital mortality nor length of hospital stay., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 van Son, Oussaada, Şekercan, Beudel, Dongelmans, van Assen, Eland, Moeniralam, Dormans, van Kalkeren, Douma, Rusch, Simsek, Liu, Kootte, Wyers, IJzerman, van den Bergh, Stehouwer, Nieuwdorp, ter Horst and Serlie.)
- Published
- 2021
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4. Metabolite Profile of Treatment-Naive Metabolic Syndrome Subjects in Relation to Cardiovascular Disease Risk.
- Author
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Warmbrunn MV, Koopen AM, de Clercq NC, de Groot PF, Kootte RS, Bouter KEC, Ter Horst KW, Hartstra AV, Serlie MJ, Ackermans MT, Soeters MR, van Raalte DH, Davids M, Nieuwdorp M, and Groen AK
- Abstract
Metabolic syndrome (MetSyn) is an important risk factor for type 2 diabetes and cardiovascular diseases (CVD). This study aimed to find distinct plasma metabolite profiles between insulin-resistant and non-insulin resistant subjects with MetSyn and evaluate if MetSyn metabolite profiles are related to CVD risk and lipid fluxes. In a cross-sectional study, untargeted metabolomics of treatment-naive males with MetSyn ( n = 132) were analyzed together with clinical parameters. In a subset of MetSyn participants, CVD risk was calculated using the Framingham score ( n = 111), and lipolysis ( n = 39) was measured by a two-step hyperinsulinemic euglycemic clamp using [1,1,2,3,3-
2 H5] glycerol to calculate lipolysis suppression rates. Peripheral insulin resistance was related to fatty acid metabolism and glycerolphosphorylcholine. Interestingly, although insulin resistance is considered to be a risk factor for CVD, we observed that there was little correspondence between metabolites associated with insulin resistance and metabolites associated with CVD risk. The latter mainly belonged to the androgenic steroid, fatty acid, phosphatidylethanolamine, and phophatidylcholine pathways. These data provide new insights into metabolic changes in mild MetSyn pathophysiology and MetSyn CVD risk related to lipid metabolism. Prospective studies may focus on the pathophysiological role of the here-identified biomarkers.- Published
- 2021
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5. Chest CT in COVID-19 at the ED: Validation of the COVID-19 Reporting and Data System (CO-RADS) and CT Severity Score: A Prospective, Multicenter, Observational Study.
- Author
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Lieveld AWE, Azijli K, Teunissen BP, van Haaften RM, Kootte RS, van den Berk IAH, van der Horst SFB, de Gans C, van de Ven PM, and Nanayakkara PWB
- Subjects
- Clinical Decision-Making, Evaluation Studies as Topic, Female, Humans, Male, Middle Aged, Mortality, Netherlands epidemiology, Prognosis, Research Design statistics & numerical data, SARS-CoV-2, Severity of Illness Index, COVID-19 diagnosis, COVID-19 epidemiology, Emergency Service, Hospital statistics & numerical data, Patient Admission statistics & numerical data, Pneumonia, Viral diagnosis, Pneumonia, Viral etiology, Radiology Information Systems organization & administration, Radiology Information Systems standards, Tomography, X-Ray Computed methods, Tomography, X-Ray Computed statistics & numerical data
- Abstract
Background: CT is thought to play a key role in coronavirus disease 2019 (COVID-19) diagnostic workup. The possibility of comparing data across different settings depends on the systematic and reproducible manner in which the scans are analyzed and reported. The COVID-19 Reporting and Data System (CO-RADS) and the corresponding CT severity score (CTSS) introduced by the Radiological Society of the Netherlands (NVvR) attempt to do so. However, this system has not been externally validated., Research Question: We aimed to prospectively validate the CO-RADS as a COVID-19 diagnostic tool at the ED and to evaluate whether the CTSS is associated with prognosis., Study Design and Methods: We conducted a prospective, observational study in two tertiary centers in The Netherlands, between March 19 and May 28, 2020. We consecutively included 741 adult patients at the ED with suspected COVID-19, who received a chest CT and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR (PCR). Diagnostic accuracy measures were calculated for CO-RADS, using PCR as reference. Logistic regression was performed for CTSS in relation to hospital admission, ICU admission, and 30-day mortality., Results: Seven hundred forty-one patients were included. We found an area under the curve (AUC) of 0.91 (CI, 0.89-0.94) for CO-RADS using PCR as reference. The optimal CO-RADS cutoff was 4, with a sensitivity of 89.4% (CI, 84.7-93.0) and specificity of 87.2% (CI, 83.9-89.9). We found a significant association between CTSS and hospital admission, ICU admission, and 30-day mortality; adjusted ORs per point increase in CTSS were 1.19 (CI, 1.09-1.28), 1.23 (1.15-1.32), 1.14 (1.07-1.22), respectively. Intraclass correlation coefficients for CO-RADS and CTSS were 0.94 (0.91-0.96) and 0.82 (0.70-0.90)., Interpretation: Our findings support the use of CO-RADS and CTSS in triage, diagnosis, and management decisions for patients presenting with possible COVID-19 at the ED., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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6. Predicting poor outcome in patients with suspected COVID-19 presenting to the Emergency Department (COVERED) - Development, internal and external validation of a prediction model.
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Azijli K, Lieveld A, van der Horst S, de Graaf N, Kootte RS, Heijmans MW, van de Ven PM, Peters E, Heijmans J, Terragnoli P, Natalini G, Abu Hilal M, de Rooij T, and Nanayakkara P
- Subjects
- Emergency Service, Hospital, Humans, Multicenter Studies as Topic, Netherlands, Prognosis, Prospective Studies, Retrospective Studies, SARS-CoV-2, COVID-19
- Abstract
Background: A recent systematic review recommends against the use of any of the current COVID-19 prediction models in clinical practice. To enable clinicians to appropriately profile and treat suspected COVID-19 patients at the emergency department (ED), externally validated models that predict poor outcome are desperately needed., Objective: Our aims were to identify predictors of poor outcome, defined as mortality or ICU admission within 30 days, in patients presenting to the ED with a clinical suspicion of COVID-19, and to develop and externally validate a prediction model for poor outcome., Methods: In this prospective, multi-center study, we enrolled suspected COVID-19 patients presenting at the EDs of two hospitals in the Netherlands. We used backward logistic regression to develop a prediction model. We used the area under the curve (AUC), Brier score and pseudo-R2 to assess model performance. The model was externally validated in an Italian cohort., Results: We included 1193 patients between March 12 and May 27 2020, of whom 196 (16.4%) had a poor outcome. We identified 10 predictors of poor outcome: current malignancy (OR 2.774; 95%CI 1.682-4.576), systolic blood pressure (OR 0.981; 95%CI 0.964-0.998), heart rate (OR 1.001; 95%CI 0.97-1.028), respiratory rate (OR 1.078; 95%CI 1.046-1.111), oxygen saturation (OR 0.899; 95%CI 0.850-0.952), body temperature (OR 0.505; 95%CI 0.359-0.710), serum urea (OR 1.404; 95%CI 1.198-1.645), C-reactive protein (OR 1.013; 95%CI 1.001-1.024), lactate dehydrogenase (OR 1.007; 95%CI 1.002-1.013) and SARS-CoV-2 PCR result (OR 2.456; 95%CI 1.526-3.953). The AUC was 0.86 (95%CI 0.83-0.89), with a Brier score of 0.32 and, and R2 of 0.41. The AUC in the external validation in 500 patients was 0.70 (95%CI 0.65-0.75)., Conclusion: The COVERED risk score showed excellent discriminatory ability, also in an external validation. It may aid clinical decision making, and improve triage at the ED in health care environments with high patient throughputs.
- Published
- 2021
7. Diagnosing COVID-19 pneumonia in a pandemic setting: Lung Ultrasound versus CT (LUVCT) - a multicentre, prospective, observational study.
- Author
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Lieveld AWE, Kok B, Schuit FH, Azijli K, Heijmans J, van Laarhoven A, Assman NL, Kootte RS, Olgers TJ, Nanayakkara PWB, and Bosch FH
- Abstract
Background: In this coronavirus disease 2019 (COVID-19) pandemic, fast and accurate testing is needed to profile patients at the emergency department (ED) and efficiently allocate resources. Chest imaging has been considered in COVID-19 workup, but evidence on lung ultrasound (LUS) is sparse. We therefore aimed to assess and compare the diagnostic accuracy of LUS and computed tomography (CT) in suspected COVID-19 patients., Methods: This multicentre, prospective, observational study included adult patients with suspected COVID-19 referred to internal medicine at the ED. We calculated diagnostic accuracy measures for LUS and CT using both PCR and multidisciplinary team (MDT) diagnosis as reference. We also assessed agreement between LUS and CT, and between sonographers., Results: One hundred and eighty-seven patients were recruited between March 19 and May 4, 2020. Area under the receiver operating characteristic (AUROC) was 0.81 (95% CI 0.75-0.88) for LUS and 0.89 (95% CI 0.84-0.94) for CT. Sensitivity and specificity for LUS were 91.9% (95% CI 84.0-96.7) and 71.0% (95% CI 61.1-79.6), respectively, versus 88.4% (95% CI 79.7-94.3) and 82.0% (95% CI 73.1-89.0) for CT. Negative likelihood ratio was 0.1 (95% CI 0.06-0.24) for LUS and 0.14 (95% CI 0.08-0.3) for CT. No patient with a false negative LUS required supplemental oxygen or admission. LUS specificity increased to 80% (95% CI 69.9-87.9) compared to MDT diagnosis, with an AUROC of 0.85 (95% CI 0.79-0.91). Agreement between LUS and CT was 0.65. Interobserver agreement for LUS was good: 0.89 (95% CI 0.83-0.93)., Conclusion: LUS and CT have comparable diagnostic accuracy for COVID-19 pneumonia. LUS can safely exclude clinically relevant COVID-19 pneumonia and may aid COVID-19 diagnosis in high prevalence situations., Competing Interests: Conflict of interest: A.W.E. Lieveld has nothing to disclose. Conflict of interest: B. Kok has nothing to disclose. Conflict of interest: F.H. Schuit has nothing to disclose. Conflict of interest: K. Azijli has nothing to disclose. Conflict of interest: J. Heijmans has nothing to disclose. Conflict of interest: A. van Laarhoven has nothing to disclose. Conflict of interest: N.L. Assman has nothing to disclose. Conflict of interest: R.S. Kootte has nothing to disclose. Conflict of interest: T.J. Olgers has nothing to disclose. Conflict of interest: P.W.B. Nanayakkara has nothing to disclose. Conflict of interest: F.H. Bosch has nothing to disclose., (Copyright ©ERS 2020.)
- Published
- 2020
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8. Added value of chest computed tomography in suspected COVID-19: an analysis of 239 patients.
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Korevaar DA, Kootte RS, Smits LP, van den Aardweg JG, Bonta PI, Schinkel J, Vigeveno RM, van den Berk IAH, Scheerder MJ, Lemkes BA, Goorhuis A, Beenen LFM, and Annema JT
- Subjects
- Aged, COVID-19, COVID-19 Testing, Clinical Laboratory Techniques, Cohort Studies, Coronavirus Infections epidemiology, Emergency Service, Hospital statistics & numerical data, Female, Hospitals, University, Humans, Male, Middle Aged, Netherlands, Pandemics, Pneumonia, Viral epidemiology, Reference Values, Retrospective Studies, Sensitivity and Specificity, Coronavirus Infections diagnosis, DNA, Viral analysis, Pneumonia, Viral diagnosis, Radiography, Thoracic methods, Real-Time Polymerase Chain Reaction methods, Tomography, X-Ray Computed methods
- Abstract
Competing Interests: Conflict of interest: D.A. Korevaar has nothing to disclose. Conflict of interest: R.S. Kootte has nothing to disclose. Conflict of interest: L.P. Smits has nothing to disclose. Conflict of interest: J.G. van den Aardweg has nothing to disclose. Conflict of interest: P.I. Bonta has nothing to disclose. Conflict of interest: J. Schinkel has nothing to disclose. Conflict of interest: R.M. Vigeveno has nothing to disclose. Conflict of interest: I.A.H. van den Berk has nothing to disclose. Conflict of interest: M.J. Scheerder has nothing to disclose. Conflict of interest: B.A. Lemkes has nothing to disclose. Conflict of interest: A. Goorhuis has nothing to disclose. Conflict of interest: L.F.M. Beenen has nothing to disclose. Conflict of interest: J.T. Annema has nothing to disclose.
- Published
- 2020
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9. Incidence of venous thromboembolism in hospitalized patients with COVID-19.
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Middeldorp S, Coppens M, van Haaps TF, Foppen M, Vlaar AP, Müller MCA, Bouman CCS, Beenen LFM, Kootte RS, Heijmans J, Smits LP, Bonta PI, and van Es N
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- Aged, Anticoagulants therapeutic use, Biomarkers, COVID-19, Catheterization, Central Venous adverse effects, Coronavirus Infections complications, Female, Fibrin Fibrinogen Degradation Products analysis, Humans, Incidence, Intensive Care Units statistics & numerical data, Male, Middle Aged, Netherlands epidemiology, Patients' Rooms statistics & numerical data, Pneumonia, Viral complications, Pulmonary Embolism blood, Pulmonary Embolism diagnostic imaging, Pulmonary Embolism etiology, Retrospective Studies, Risk Factors, SARS-CoV-2, Thrombophilia drug therapy, Thrombophilia etiology, Thrombophlebitis epidemiology, Thrombophlebitis etiology, Venous Thromboembolism blood, Venous Thromboembolism diagnostic imaging, Venous Thromboembolism etiology, Venous Thrombosis blood, Venous Thrombosis diagnostic imaging, Venous Thrombosis etiology, Betacoronavirus, Coronavirus Infections blood, Pandemics, Pneumonia, Viral blood, Pulmonary Embolism epidemiology, Venous Thromboembolism epidemiology, Venous Thrombosis epidemiology
- Abstract
Background: Coronavirus disease 2019 (COVID-19) can lead to systemic coagulation activation and thrombotic complications., Objectives: To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID-19., Methods: Single-center cohort study of 198 hospitalized patients with COVID-19., Results: Seventy-five patients (38%) were admitted to the intensive care unit (ICU). At time of data collection, 16 (8%) were still hospitalized and 19% had died. During a median follow-up of 7 days (IQR, 3-13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis. The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10-22), 33% (95% CI, 23-43) and 42% (95% CI 30-54) respectively. For symptomatic VTE, these were 10% (95% CI, 5.8-16), 21% (95% CI, 14-30) and 25% (95% CI 16-36). VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02-5.5). The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17-37), 47% (95% CI, 34-58), and 59% (95% CI, 42-72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4-15), 9.2% (95% CI, 2.6-21), and 9.2% (2.6-21) at 7, 14, and 21 days)., Conclusions: The observed risk for VTE in COVID-19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE. Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival., (© 2020 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)
- Published
- 2020
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10. Plasma Metabolites Related to Peripheral and Hepatic Insulin Sensitivity Are Not Directly Linked to Gut Microbiota Composition.
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Koopen AM, de Clercq NC, Warmbrunn MV, Herrema H, Davids M, de Groot PF, Kootte RS, Bouter KEC, Nieuwdorp M, Groen AK, and Prodan A
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- Cross-Sectional Studies, Fasting blood, Feces microbiology, Female, Glucose Clamp Technique, Humans, Liver physiopathology, Male, Middle Aged, RNA, Ribosomal, 16S analysis, Gastrointestinal Microbiome physiology, Insulin Resistance physiology, Metabolic Syndrome blood, Metabolic Syndrome microbiology, Metabolome
- Abstract
Plasma metabolites affect a range of metabolic functions in humans, including insulin sensitivity (IS). A subset of these plasma metabolites is modified by the gut microbiota. To identify potential microbial-metabolite pathways involved in IS, we investigated the link between plasma metabolites, gut microbiota composition, and IS, using the gold-standard for peripheral and hepatic IS measurement in a group of participants with metabolic syndrome (MetSyn). In a cross-sectional study with 115 MetSyn participants, fasting plasma samples were collected for untargeted metabolomics analysis and fecal samples for 16S rRNA gene amplicon sequencing. A two-step hyperinsulinemic euglycemic clamp was performed to assess peripheral and hepatic IS. Collected data were integrated and potential interdependence between metabolites, gut microbiota, and IS was analyzed using machine learning prediction models. Plasma metabolites explained 13.2% and 16.7% of variance in peripheral and hepatic IS, respectively. Fecal microbiota composition explained 4.2% of variance in peripheral IS and was not related to hepatic IS. Although metabolites could partially explain the variances in IS, the top metabolites related to peripheral and hepatic IS did not significantly correlate with gut microbiota composition (both on taxonomical level and alpha-diversity). However, all plasma metabolites could explain 18.5% of the variance in microbial alpha-diversity (Shannon); the top 20 metabolites could even explain 44.5% of gut microbial alpha-diversity. In conclusion, plasma metabolites could partially explain the variance in peripheral and hepatic IS; however, these metabolites were not directly linked to the gut microbiota composition, underscoring the intricate relation between plasma metabolites, the gut microbiota, and IS in MetSyn.
- Published
- 2020
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11. Individual and cohort-specific gut microbiota patterns associated with tissue-specific insulin sensitivity in overweight and obese males.
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Hermes GDA, Reijnders D, Kootte RS, Goossens GH, Smidt H, Nieuwdorp M, Blaak EE, and Zoetendal EG
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- Adipose Tissue metabolism, Adult, Aged, Area Under Curve, Body Mass Index, Cross-Sectional Studies, Glucose Clamp Technique, Homeostasis, Humans, Insulin Resistance, Liver metabolism, Male, Metabolic Syndrome metabolism, Middle Aged, Netherlands, Phenotype, Phylogeny, Prediabetic State metabolism, Principal Component Analysis, Prognosis, Gastrointestinal Microbiome, Insulin metabolism, Obesity microbiology, Overweight microbiology
- Abstract
A growing body of evidence suggests that the human gut microbiota plays a role in the development of obesity and related metabolic diseases. However, there is little consensus between studies, which could be due to biological as well as technical variation. In addition, little human data are available to investigate whether tissue-specific insulin sensitivity is related to specific microbial patterns. We examined this relation in two independent cohorts of overweight and obese pre-diabetic men, using phylogenetic microarray data and hepatic, peripheral and adipose tissue insulin sensitivity that were determined by a two-step hyperinsulinemic-euglycemic clamp with [6,6-
2 H2 ]-glucose tracer infusion. Despite a prominent subject-specific microbiota, we found significant associations of microbial taxa with tissue-specific insulin sensitivity using regression analysis. Using random forests we found moderate associations with other measures of glucose homeostasis in only one of the cohorts (fasting glucose concentrations AUC = 0.66 and HbA1c AUC = 0.65). However, all findings were cohort-specific due to pronounced variation in microbiota between cohorts, suggesting the existence of alternative states for dysbiosis in metabolic syndrome patients. Our findings suggest individual or group related dynamics, instead of universal microbiota signals, related to the host when the overweight or obese state has already developed and argue that care should be taken with extrapolating significant correlations from single cohorts, into generalized biological relevance.- Published
- 2020
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12. The intestinal microbiome potentially affects thrombin generation in human subjects.
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Mohammed Y, Kootte RS, Kopatz WF, Borchers CH, Büller HR, Versteeg HH, Nieuwdorp M, and van Mens TE
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- Fecal Microbiota Transplantation, Feces, Humans, Research Subjects, Thrombin, Gastrointestinal Microbiome
- Abstract
Background: The intestinal microbiome plays a versatile role in the etiology of arterial thrombosis. In venous thrombosis, driven chiefly by plasma coagulation, no such role has yet been established. We hypothesized that the intestinal microbiome composition affects coagulation in humans., Methods: We used healthy donor fecal microbiota transplant (FMT) to experimentally change the microbiome composition in metabolic syndrome patients. Thirty-five subjects were randomized in a blinded fashion to healthy donor FMT or autologous FMT as a control in a 2:1 ratio. We measured thrombin generation at baseline and after 6 weeks using automated calibrated thrombinography, and we determined plasma abundance of 32 coagulation related proteins using a targeted mass spectrometry-based quantitative proteomics assay with heavy labeled internal standards., Results: Healthy donor FMT prolonged the thrombinography lag time (median delta 0.0 versus 0.25 minutes, P = .039). The other thrombinography parameters showed no significant difference. Unsupervised cluster analysis suggested overall downregulation of coagulation related plasma proteins in subject clusters containing predominantly subjects that had a metabolic response to healthy donor FMT. FMT treatment status itself showed no clear clustering pattern with up- or downregulation, however, and proteins did not cluster according to an apparent biological grouping., Discussion: A single healthy donor FMT tends to modestly suppress the onset thrombin generation in metabolic syndrome patients, representing initial proof-of-principle that the intestinal microbiota composition might affect the coagulation system in humans. The findings merit external validation as a role for intestinal microbiota in coagulation can have clinically important implications., (© 2019 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.)
- Published
- 2020
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13. Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline-Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome.
- Author
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Smits LP, Kootte RS, Levin E, Prodan A, Fuentes S, Zoetendal EG, Wang Z, Levison BS, Cleophas MCP, Kemper EM, Dallinga-Thie GM, Groen AK, Joosten LAB, Netea MG, Stroes ESG, de Vos WM, Hazen SL, and Nieuwdorp M
- Subjects
- Adult, Aged, Carnitine metabolism, Double-Blind Method, Feces microbiology, Humans, Male, Metabolic Syndrome diagnosis, Metabolic Syndrome microbiology, Middle Aged, Netherlands, Pilot Projects, Time Factors, Treatment Outcome, Vasculitis diagnosis, Vasculitis microbiology, Young Adult, Bacteria metabolism, Choline metabolism, Cytokines metabolism, Diet, Vegan, Fecal Microbiota Transplantation adverse effects, Gastrointestinal Microbiome, Inflammation Mediators metabolism, Metabolic Syndrome therapy, Methylamines metabolism, Vasculitis therapy
- Abstract
Background: Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge., Methods and Results: We performed a double-blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan-donor or autologous fecal microbiota transplantation. At baseline and 2 weeks thereafter, we determined the ability to produce TMAO from d
6 -choline and d3 -carnitine (eg, labeled and unlabeled TMAO in plasma and 24-hour urine after oral ingestion of 250 mg of both isotope-labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition.18 F-fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as ex vivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan-donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan-donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic18 F-fluorodeoxyglucose uptake, or ex vivo cytokine production from peripheral blood mononuclear cells., Conclusions: Single lean vegan-donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation., Clinical Trial Registration: URL: http://www.trialregister.nl. Unique identifier: NTR 4338., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)- Published
- 2018
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14. Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition.
- Author
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Kootte RS, Levin E, Salojärvi J, Smits LP, Hartstra AV, Udayappan SD, Hermes G, Bouter KE, Koopen AM, Holst JJ, Knop FK, Blaak EE, Zhao J, Smidt H, Harms AC, Hankemeijer T, Bergman JJGHM, Romijn HA, Schaap FG, Olde Damink SWM, Ackermans MT, Dallinga-Thie GM, Zoetendal E, de Vos WM, Serlie MJ, Stroes ESG, Groen AK, and Nieuwdorp M
- Subjects
- Blood Glucose analysis, Blood Glucose metabolism, Feces microbiology, Humans, Male, Metabolic Syndrome blood, Metabolic Syndrome metabolism, Metabolic Syndrome microbiology, Middle Aged, Transplantation, Autologous methods, Transplantation, Homologous methods, gamma-Aminobutyric Acid blood, gamma-Aminobutyric Acid metabolism, Fecal Microbiota Transplantation methods, Gastrointestinal Microbiome, Insulin Resistance, Metabolic Syndrome therapy
- Abstract
The intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We therefore studied the effect of lean donor (allogenic) versus own (autologous) fecal microbiota transplantation (FMT) to male recipients with the metabolic syndrome. Whereas we did not observe metabolic changes at 18 weeks after FMT, insulin sensitivity at 6 weeks after allogenic FMT was significantly improved, accompanied by altered microbiota composition. We also observed changes in plasma metabolites such as γ-aminobutyric acid and show that metabolic response upon allogenic FMT (defined as improved insulin sensitivity 6 weeks after FMT) is dependent on decreased fecal microbial diversity at baseline. In conclusion, the beneficial effects of lean donor FMT on glucose metabolism are associated with changes in intestinal microbiota and plasma metabolites and can be predicted based on baseline fecal microbiota composition., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
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15. Hepatitis E during lenalidomide treatment for multiple myeloma in complete remission.
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Kootte RS and Faber LM
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- Aged, Female, Humans, Lenalidomide, Liver Function Tests, Maintenance Chemotherapy, Thalidomide adverse effects, Transaminases blood, Hepatitis E chemically induced, Immunologic Factors adverse effects, Multiple Myeloma drug therapy, Thalidomide analogs & derivatives
- Abstract
Lenalidomide has a central role in the treatment of multiple myeloma and results in improved survival. As with other chemotherapeutics, it can cause several serious side effects. This is the first reported case of hepatitis E during lenalidomide treatment for multiple myeloma in complete remission. In case of liver chemistry abnormalities during lenalidomide treatment, the differential diagnosis should include hepatitis E infection.
- Published
- 2017
16. Intravascular Lipiodol Presenting as an Atrial Mass.
- Author
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Kootte RS, Haeck JD, van Lienden KP, van Boven WJ, van der Wal AC, and de Boer HH
- Subjects
- Aged, Female, Humans, Embolization, Therapeutic adverse effects, Ethiodized Oil adverse effects, Heart Atria pathology, Heart Diseases etiology, Thrombosis etiology, Vena Cava, Inferior pathology
- Abstract
A 68-year-old woman, previously treated with embolization of the thoracic duct with Lipiodol (an ethiodized oil injection) and cyanoacrylate glue (a topical tissue adhesive), was admitted with an asymptomatic mass in the inferior vena cava (IVC) and right atrium. The mass was surgically removed, and pathologic analysis revealed a Lipiodol-containing thrombus. To our knowledge, this is the first clinicopathologic report of Lipiodol-induced thrombus presenting as an intracavitary mass., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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17. Transintestinal Cholesterol Transport Is Active in Mice and Humans and Controls Ezetimibe-Induced Fecal Neutral Sterol Excretion.
- Author
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Jakulj L, van Dijk TH, de Boer JF, Kootte RS, Schonewille M, Paalvast Y, Boer T, Bloks VW, Boverhof R, Nieuwdorp M, Beuers UH, Stroes ES, and Groen AK
- Subjects
- ATP Binding Cassette Transporter, Subfamily G, Member 8 deficiency, ATP Binding Cassette Transporter, Subfamily G, Member 8 metabolism, Adult, Animals, Bile chemistry, Bile Acids and Salts metabolism, Biological Transport drug effects, Cholesterol blood, Female, Humans, Intestines drug effects, Kinetics, Lipoproteins deficiency, Lipoproteins metabolism, Male, Mice, Inbred C57BL, Middle Aged, Cholesterol metabolism, Ezetimibe pharmacology, Feces chemistry, Intestinal Mucosa metabolism
- Abstract
Except for conversion to bile salts, there is no major cholesterol degradation pathway in mammals. Efficient excretion from the body is therefore a crucial element in cholesterol homeostasis. Yet, the existence and importance of cholesterol degradation pathways in humans is a matter of debate. We quantified cholesterol fluxes in 15 male volunteers using a cholesterol balance approach. Ten participants repeated the protocol after 4 weeks of treatment with ezetimibe, an inhibitor of intestinal and biliary cholesterol absorption. Under basal conditions, about 65% of daily fecal neutral sterol excretion was bile derived, with the remainder being contributed by direct transintestinal cholesterol excretion (TICE). Surprisingly, ezetimibe induced a 4-fold increase in cholesterol elimination via TICE. Mouse studies revealed that most of ezetimibe-induced TICE flux is mediated by the cholesterol transporter Abcg5/Abcg8. In conclusion, TICE is active in humans and may serve as a novel target to stimulate cholesterol elimination in patients at risk for cardiovascular disease., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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18. Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans: A Randomized Double-Blind Placebo-Controlled Trial.
- Author
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Reijnders D, Goossens GH, Hermes GD, Neis EP, van der Beek CM, Most J, Holst JJ, Lenaerts K, Kootte RS, Nieuwdorp M, Groen AK, Olde Damink SW, Boekschoten MV, Smidt H, Zoetendal EG, Dejong CH, and Blaak EE
- Published
- 2016
- Full Text
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19. Insulin resistance in obesity can be reliably identified from fasting plasma insulin.
- Author
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ter Horst KW, Gilijamse PW, Koopman KE, de Weijer BA, Brands M, Kootte RS, Romijn JA, Ackermans MT, Nieuwdorp M, Soeters MR, and Serlie MJ
- Subjects
- Adult, Body Mass Index, Fasting metabolism, Glucose Clamp Technique, Humans, Hypoglycemic Agents therapeutic use, Insulin therapeutic use, Male, Middle Aged, Muscle, Skeletal metabolism, Netherlands epidemiology, Obesity, Predictive Value of Tests, Reference Values, Adipose Tissue, White metabolism, Blood Glucose metabolism, Hypoglycemic Agents blood, Insulin blood, Insulin Resistance, Liver metabolism
- Abstract
Background/objectives: Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely measured variables., Subjects/methods: We assembled data from non-obese (n=112) and obese (n=100) men who underwent two-step EHCs using [6,6-(2)H2]glucose as tracer (insulin infusion dose 20 and 60 mU m(-2) min(-1), respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified., Results: Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (Rd) were 46.5% and 37.3 μmol kg(-)(1) min(-)(1), respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had Rd within the reference range. Obese men with Rd <37.3 μmol kg(-1) min(-1) did not differ from insulin-sensitive obese men in age, body mass index (BMI), body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110±49 vs 63±29 pmol l(-1), P<0.001) and homeostasis model assessment of insulin resistance (HOMA-IR) (4.5±2.2 vs 2.7±1.4, P=0.004). Insulin-resistant obese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol l(-1)., Conclusions: Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l(-1) with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings.
- Published
- 2015
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20. Myocardial infarction in a 36-year-old man with combined ABCA1 and APOA-1 deficiency.
- Author
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van Capelleveen JC, Kootte RS, Hovingh GK, and Bochem AE
- Subjects
- Adult, Humans, Male, ATP Binding Cassette Transporter 1 deficiency, Apolipoprotein A-I deficiency, Lipoproteins, HDL metabolism, Mutation, Myocardial Infarction genetics, Myocardial Infarction metabolism
- Abstract
In this report, we present a patient who suffered from a myocardial infarction at an extremely young age. The only remarkable finding in the risk factor workup was a near undetectable high-density lipoprotein (HDL)-cholesterol plasma level (0.09 mmol/L). Genetic analysis of key genes involved in HDL metabolism resulted in the discovery of 2 very rare mutations in the ABCA1 and APOA1 genes. We discuss the effects of these mutations on HDL metabolism and reverse cholesterol transport and interpret these findings in relation to the extensive atherosclerosis at a very young age in this patient., (Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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21. Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT and artery wall thickness in patients with FHA.
- Author
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Kootte RS, Smits LP, van der Valk FM, Dasseux JL, Keyserling CH, Barbaras R, Paolini JF, Santos RD, van Dijk TH, Dallinga-van Thie GM, Nederveen AJ, Mulder WM, Hovingh GK, Kastelein JP, Groen AK, and Stroes E
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Radiography, Apolipoprotein A-I administration & dosage, Carotid Arteries diagnostic imaging, Carotid Arteries metabolism, Cholesterol, HDL blood, Hypoalphalipoproteinemias blood, Hypoalphalipoproteinemias diagnostic imaging, Hypoalphalipoproteinemias drug therapy, Magnetic Resonance Angiography, Phospholipids administration & dosage, Positron-Emission Tomography, Recombinant Proteins administration & dosage
- Abstract
Reverse cholesterol transport (RCT) contributes to the anti-atherogenic effects of HDL. Patients with the orphan disease, familial hypoalphalipoproteinemia (FHA), are characterized by decreased tissue cholesterol removal and an increased atherogenic burden. We performed an open-label uncontrolled proof-of-concept study to evaluate the effect of infusions with a human apoA-I-containing HDL-mimetic particle (CER-001) on RCT and the arterial vessel wall in FHA. Subjects received 20 infusions of CER-001 (8 mg/kg) during 6 months. Efficacy was assessed by measuring (apo)lipoproteins, plasma-mediated cellular cholesterol efflux, fecal sterol excretion (FSE), and carotid artery wall dimension by MRI and artery wall inflammation by (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography scans. We included seven FHA patients: HDL-cholesterol (HDL-c), 13.8 [1.8-29.1] mg/dl; apoA-I, 28.7 [7.9-59.1] mg/dl. Following nine infusions in 1 month, apoA-I and HDL-c increased directly after infusion by 27.0 and 16.1 mg/dl (P = 0.018). CER-001 induced a 44% relative increase (P = 0.018) in in vitro cellular cholesterol efflux with a trend toward increased FSE (P = 0.068). After nine infusions of CER-001, carotid mean vessel wall area decreased compared with baseline from 25.0 to 22.8 mm(2) (P = 0.043) and target-to-background ratio from 2.04 to 1.81 (P = 0.046). In FHA-subjects, CER-001 stimulates cholesterol mobilization and reduces artery wall dimension and inflammation, supporting further evaluation of CER-001 in FHA patients., (Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.)
- Published
- 2015
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22. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity.
- Author
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Vrieze A, Out C, Fuentes S, Jonker L, Reuling I, Kootte RS, van Nood E, Holleman F, Knaapen M, Romijn JA, Soeters MR, Blaak EE, Dallinga-Thie GM, Reijnders D, Ackermans MT, Serlie MJ, Knop FK, Holst JJ, van der Ley C, Kema IP, Zoetendal EG, de Vos WM, Hoekstra JB, Stroes ES, Groen AK, and Nieuwdorp M
- Subjects
- Administration, Oral, Adult, Aged, Animals, Anti-Bacterial Agents adverse effects, Bile Acids and Salts blood, Feces chemistry, Feces microbiology, Glucose metabolism, Humans, Male, Metabolic Syndrome complications, Metabolic Syndrome drug therapy, Metabolic Syndrome microbiology, Mice, Middle Aged, Obesity complications, Obesity drug therapy, Obesity microbiology, Single-Blind Method, Vancomycin adverse effects, Anti-Bacterial Agents administration & dosage, Bile Acids and Salts metabolism, Insulin Resistance, Intestines drug effects, Intestines microbiology, Microbiota drug effects, Vancomycin administration & dosage
- Abstract
Background & Aims: Obesity has been associated with changes in the composition and function of the intestinal microbiota. Modulation of the microbiota by antibiotics also alters bile acid and glucose metabolism in mice. Hence, we hypothesized that short term administration of oral antibiotics in humans would affect fecal microbiota composition and subsequently bile acid and glucose metabolism., Methods: In this single blinded randomized controlled trial, 20 male obese subjects with metabolic syndrome were randomized to 7 days of amoxicillin 500 mg t.i.d. or 7 days of vancomycin 500 mg t.i.d. At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured., Results: Vancomycin reduced fecal microbial diversity with a decrease of gram-positive bacteria (mainly Firmicutes) and a compensatory increase in gram-negative bacteria (mainly Proteobacteria). Concomitantly, vancomycin decreased fecal secondary bile acids with a simultaneous postprandial increase in primary bile acids in plasma (p<0.05). Moreover, changes in fecal bile acid concentrations were predominantly associated with altered Firmicutes. Finally, administration of vancomycin decreased peripheral insulin sensitivity (p<0.05). Amoxicillin did not affect any of these parameters., Conclusions: Oral administration of vancomycin significantly impacts host physiology by decreasing intestinal microbiota diversity, bile acid dehydroxylation and peripheral insulin sensitivity in subjects with metabolic syndrome. These data show that intestinal microbiota, particularly of the Firmicutes phylum contributes to bile acid and glucose metabolism in humans. This trial is registered at the Dutch Trial Register (NTR2566)., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
- Published
- 2014
- Full Text
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23. Reversal of atherosclerosis with apolipoprotein A1: back to basics.
- Author
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Smits LP, Kootte RS, and Stroes ES
- Subjects
- Animals, Apolipoprotein A-I pharmacology, Humans, Male, Phospholipids pharmacology, Apolipoprotein A-I chemistry, Atherosclerosis drug therapy, Biomimetics, Lipoproteins, HDL blood, Phospholipids chemistry, Recombinant Proteins pharmacology
- Published
- 2014
- Full Text
- View/download PDF
24. Pro-atherogenic lipid changes and decreased hepatic LDL receptor expression by tocilizumab in rheumatoid arthritis.
- Author
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Strang AC, Bisoendial RJ, Kootte RS, Schulte DM, Dallinga-Thie GM, Levels JH, Kok M, Vos K, Tas SW, Tietge UJ, Müller N, Laudes M, Gerlag DM, Stroes ES, and Tak PP
- Subjects
- Adult, Aged, Antibodies, Monoclonal, Humanized administration & dosage, Antioxidants metabolism, Antirheumatic Agents administration & dosage, Antirheumatic Agents adverse effects, Arthritis, Rheumatoid epidemiology, Arthritis, Rheumatoid metabolism, Cardiovascular Diseases epidemiology, Female, Gene Expression drug effects, Hep G2 Cells, Humans, Infusions, Intravenous, Liver drug effects, Liver physiology, Male, Middle Aged, Morbidity, Receptors, LDL metabolism, Antibodies, Monoclonal, Humanized adverse effects, Arthritis, Rheumatoid drug therapy, Cardiovascular Diseases metabolism, Lipids blood, Receptors, LDL genetics
- 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., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2013
- Full Text
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25. Obesity, non-alcoholic fatty liver disease, and atherothrombosis: a role for the intestinal microbiota?
- Author
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Knaapen M, Kootte RS, Zoetendal EG, de Vos WM, Dallinga-Thie GM, Levi M, Stroes ES, and Nieuwdorp M
- Subjects
- Humans, Non-alcoholic Fatty Liver Disease, Atherosclerosis etiology, Fatty Liver etiology, Gastrointestinal Tract microbiology, Metagenome, Obesity etiology
- Abstract
Whereas the association between intestinal microorganisms and health has been widely accepted in the area of infectious disease, recent advances have now implied a role for the intestinal microbiota in human energy balance. In fact, numerous studies support an intricate relationship between the intestinal microbiota and obesity, as well as subsequent insulin resistance and non-alcoholic fatty liver disease. Intestinal microorganisms also seem to be involved in haemostatic tone and atherogenesis. However, as most of the findings stem from observational data, intervention studies in humans using interventions selectively aimed at altering the composition and activity of the intestinal microbiota are crucial to prove causality. If substantiated, this could open the arena for modulation of the intestinal microbiota as a future target in obesity-associated disease, both as a diagnostic test for personalized algorithms and for selective therapeutic strategies., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)
- Published
- 2013
- Full Text
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26. Fecal transplant: a safe and sustainable clinical therapy for restoring intestinal microbial balance in human disease?
- Author
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Vrieze A, de Groot PF, Kootte RS, Knaapen M, van Nood E, and Nieuwdorp M
- Subjects
- Humans, Probiotics, Biological Therapy methods, Feces microbiology, Gastrointestinal Diseases therapy, Gastrointestinal Tract microbiology, Host-Pathogen Interactions physiology, Metagenome physiology
- Abstract
Recent studies have suggested an association between intestinal microbiota composition and human disease, however causality remains to be proven. With hindsight, the application of fecal transplantation (FMT) does indeed suggest a causal relation between interfering with gut microbiota composition and a resultant cure of several disease states. In this review, we aim to show the available evidence regarding the involvement of intestinal microbiota and human (autoimmune) disease. Moreover, we refer to (mostly case report) studies showing beneficial or adverse effects of fecal transplantation on clinical outcomes in some of these disease states. If these findings can be substantiated in larger randomized controlled double blind trials also implementing gut microbiota composition before and after intervention, fecal transplantation might provide us with novel insights into causally related intestinal microbiota, that might be serve as future diagnostic and treatment targets in human disease., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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27. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome.
- Author
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Vrieze A, Van Nood E, Holleman F, Salojärvi J, Kootte RS, Bartelsman JF, Dallinga-Thie GM, Ackermans MT, Serlie MJ, Oozeer R, Derrien M, Druesne A, Van Hylckama Vlieg JE, Bloks VW, Groen AK, Heilig HG, Zoetendal EG, Stroes ES, de Vos WM, Hoekstra JB, and Nieuwdorp M
- Subjects
- Adult, Alcaligenes faecalis, Bacteroidetes, Body Mass Index, Clostridium, Escherichia coli, Eubacterium, Fatty Acids, Volatile metabolism, Feces chemistry, Humans, Male, Metabolic Syndrome blood, Middle Aged, Oxalobacter formigenes, Statistics, Nonparametric, Blood Glucose metabolism, Feces microbiology, Insulin Resistance, Intestine, Small microbiology, Metabolic Syndrome therapy, Metagenome
- Abstract
Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned randomly to groups that were given small intestinal infusions of allogenic or autologous microbiota. Six weeks after infusion of microbiota from lean donors, insulin sensitivity of recipients increased (median rate of glucose disappearance changed from 26.2 to 45.3 μmol/kg/min; P < .05) along with levels of butyrate-producing intestinal microbiota. Intestinal microbiota might be developed as therapeutic agents to increase insulin sensitivity in humans; www.trialregister.nl; registered at the Dutch Trial Register (NTR1776)., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2012
- Full Text
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28. The incidence of venous thromboembolism in patients with overt hyperthyroidism: a retrospective multicentre cohort study.
- Author
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Kootte RS, Stuijver DJ, Dekkers OM, van Zaane B, Fliers E, Cannegieter SC, and Gerdes VE
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Cohort Studies, Female, Graves Disease blood, Graves Disease complications, Humans, Hyperthyroidism blood, Hyperthyroidism complications, Incidence, Male, Middle Aged, Netherlands, Retrospective Studies, Risk, Venous Thromboembolism blood, Venous Thromboembolism etiology, Young Adult, Graves Disease epidemiology, Hyperthyroidism epidemiology, Venous Thromboembolism epidemiology
- Abstract
Hyperthyroidism is associated with several changes in the haemostatic system resulting in a hypercoagulable state. It is uncertain at this stage whether this leads to an increased risk of venous thromboembolism (VTE). The aim of this retrospective cohort study was to determine the risk of VTE in all patients with overt hyperthyroidism and to compare this to the risk of VTE in the general population. In three hospitals in the Netherlands, patients with biochemically confirmed hyperthyroidism caused by Graves' disease, multinodular goiter or toxic adenoma were included. All available electronic and handwritten records were examined. Primary outcome was the occurrence of VTE within six months before and until six months after the diagnosis of hyperthyroidism. We included a total of 587 patients. Five patients experienced a VTE during the study period, resulting in an incidence rate of 8.7 (95% CI 2.8 - 20.2) per 1,000 person-years. Three of these five patients had a first VTE (incidence rate for first VTE was 5.3 [95% CI 1.1 - 15.6] per 1,000 person-years). Incidence rates of VTE in the general population are between 0.6 and 1.6 per 1,000 person-years for first VTE and 0.7 and 1.8 per 1,000 person-years for all VTE. In conclusion, the incidence rate of VTE in patients with hyperthyroidism appears to be high. Future prospective studies are needed to further explore this possible association and to address its clinical implications.
- Published
- 2012
- Full Text
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29. The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus.
- Author
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Kootte RS, Vrieze A, Holleman F, Dallinga-Thie GM, Zoetendal EG, de Vos WM, Groen AK, Hoekstra JB, Stroes ES, and Nieuwdorp M
- Subjects
- Animals, Anti-Bacterial Agents therapeutic use, Bariatric Surgery, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 physiopathology, Diet, Gastrointestinal Tract metabolism, Gastrointestinal Tract physiopathology, Humans, Mice, Obesity metabolism, Obesity physiopathology, Prebiotics, Probiotics therapeutic use, Bile Acids and Salts metabolism, Diabetes Mellitus, Type 2 microbiology, Fatty Acids, Volatile metabolism, Gastrointestinal Tract microbiology, Metagenome, Obesity microbiology
- Abstract
Obesity and type 2 diabetes mellitus (T2DM) are attributed to a combination of genetic susceptibility and lifestyle factors. Their increasing prevalence necessitates further studies on modifiable causative factors and novel treatment options. The gut microbiota has emerged as an important contributor to the obesity--and T2DM--epidemic proposed to act by increasing energy harvest from the diet. Although obesity is associated with substantial changes in the composition and metabolic function of the gut microbiota, the pathophysiological processes remain only partly understood. In this review we will describe the development of the adult human microbiome and discuss how the composition of the gut microbiota changes in response to modulating factors. The influence of short-chain fatty acids, bile acids, prebiotics, probiotics, antibiotics and microbial transplantation is discussed from studies using animal and human models. Ultimately, we aim to translate these findings into therapeutic pathways for obesity and T2DM in humans., (© 2011 Blackwell Publishing Ltd.)
- Published
- 2012
- Full Text
- View/download PDF
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