Douwe J Mulder

Douwe J Mulder
University of Groningen | RUG · Department of Internal Medicine

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82
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Publications

Publications (82)
Article
Aims Calciprotein particles (CPPs) are circulating calcium and phosphate nanoparticles associated with development of vascular calcification (VC) in chronic kidney disease (CKD). Although recent studies have been focusing on associations of CPPs with presence of VC in CKD, insights in the underlying processes and mechanisms by which CPPs might aggr...
Article
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Objective To identify differences in levels of serum biomarkers associated with atherosclerosis between anti-citrullinated protein antibodies (ACPA) positive groups. Methods Cross-sectional data were used from the Dutch Lifelines Cohort Study combined with data derived from RA risk and early RA studies conducted at the University Medical Center Gr...
Article
Objectives: Scleroderma is a heterogeneous chronic autoimmune disease affecting connective tissue, characterised by chronic inflammation and fibrosis, particularly affecting internal organs and skin. Orofacial involvement is common, leading to facial atrophy, mask-like appearance and difficulties in function that significantly impact patients' qua...
Article
Background Systemic inflammation plays a pivotal role in the development of type 2 diabetes (T2D). Here we hypothesized that circulating levels of calprotectin, a myeloid cell-derived biomarker of inflammation, is associated with the development of new-onset T2D in the general population. Methods A total of 4,815 initially non-diabetic participant...
Article
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Introduction Systemic inflammation has been associated with chronic kidney disease (CKD). In this study, we aimed to investigate a potential association between the plasma biomarker of inflammation calprotectin and new-onset CKD in a population-based cohort study. Methods Individuals without CKD at baseline (n=4,662) who participated in the Prevent...
Article
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Background Cardiovascular disease is the most common cause of death worldwide, including infection and inflammation related conditions. Multiple studies have demonstrated potential advantages of hybrid positron emission tomography combined with computed tomography (PET/CT) as an adjunct to current clinical inflammatory and infectious biochemical ma...
Article
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BACKGROUND: Low‐grade systemic inflammation is a relevant pathogenic mechanism underlying the development of hypertension. In this study, we hypothesized that plasma calprotectin levels, as a biomarker of neutrophil‐mediated inflammation, is associated with developing new‐onset hypertension in the general population. METHODS AND RESULTS: Plasma cal...
Article
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Introduction Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) are the leading causes of death in systemic sclerosis (SSc). Until now, no prospective biomarker to predict new onset of SSc-ILD or SSc-PAH in patients with SSc has reached clinical application. In homeostasis, the receptor for advanced glycation end products (RA...
Article
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Inflammatory abdominal aortic aneurysms (iAAA) are a form of noninfectious aortitis in patients with abdominal aortic aneurysms (AAA). Ultrasound could help to detect iAAA early. This retrospective observational study assessed the potential of using ultrasound to detect iAAA in a case series of iAAA patients, and the diagnostic value of ultrasound...
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Raynaud’s Phenomenon (RP) leading to repetitive ischemia and reperfusion (IR) stress, is the first recognizable sign of systemic sclerosis (SSc) leading to increased oxidative stress. High-mobility group box-1 (HMGB1) is a nuclear factor released by apoptotic and necrotic cells after oxidative stress. Since HMGB1 can signal through the receptor for...
Article
Sodium-glucose co-transporter 2 (SGLT2) inhibitors, including canagliflozin, reduce the risk of cardiovascular and kidney outcomes in patients with and without type 2 diabetes, albeit with a large inter-individual variation. The underlying mechanisms for this variation in response might be attributed to differences in SGLT2 occupancy, resulting fro...
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Circulating levels of neutrophil gelatinase-associated lipocalin (NGAL) have been associated with acute kidney injury and the severity and progression of chronic kidney disease (CKD). This study investigated its potential utility as a biomarker for the risk of new-onset CKD in a population-based cohort study. Individuals without CKD at baseline (n...
Article
Systemic vasculitides comprise a group of autoimmune diseases affecting blood vessels. [18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) plays an important role in the diagnosis and therapeutic monitoring of vasculitides affecting large-sized and medium-sized vessels. FDG-PET/CT also provides complementary...
Article
Vitamin K deficiency is common among kidney transplant recipients (KTRs) and likely contributes to progressive vascular calcification and stiffness. In this single-center, randomized, double-blind, placebo-controlled trial, we aimed to investigate the effects of vitamin K supplementation on the primary end point, serum calcification propensity (cal...
Article
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The detection of occult infections and low-grade inflammation in clinical practice remains challenging and much depending on readers’ expertise. Although molecular imaging, like [¹⁸F]FDG PET or radiolabeled leukocyte scintigraphy, offers quantitative and reproducible whole body data on inflammatory responses its interpretation is limited to visual...
Article
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The angiotensin receptor blocker telmisartan slows progression of kidney disease in patients with type 2 diabetes (T2D), yet many patients remain at high risk for progressive kidney function loss. The underlying mechanisms for this response variation might be attributed to differences in angiotensin‐1 receptor occupancy (RO), resulting from individ...
Article
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Systemic Sclerosis (SSc) is a multiphase autoimmune disease with a well-known triad of clinical manifestations including vasculopathy, inflammation and fibrosis. Although a plethora of drugs has been suggested as potential candidates to halt SSc progression, nothing has proven clinically efficient. In SSc, both innate and adaptive immune systems ar...
Article
Objective : Follow-up of patients with treatment-resistant Raynaud's phenomenon (RP) one-year after single-port thoracoscopic sympathicotomy (SPTS). Methods : Eight patients (six males, two females, median age of 45 years) with treatment-resistant RP underwent left-sided SPTS at the third rib (R3), unilaterally. Questionnaires were taken, and numb...
Article
Background Oxidative stress is known to be involved in the development of hypertension, but accurate redox biomarkers predicting the risk of developing hypertension are scarce. Serum free sulfhydryl groups (R–SH, free thiols) have been shown to accurately reflect systemic oxidative stress in various conditions. In this study, we aimed to investigat...
Poster
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Background ILD is a major problem in SSc for which no disease-modifying therapies are available. Many observations suggest monocyte/macrophage involvement in SSc and might be a key component in the development of ILD. Macrophages polarize into M1 and M2 phenotypes and thereby orchestrate inflammation and subsequent fibrosis by responding to and pro...
Article
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Background Nailfold capillary microscopy (NCM) is a cornerstone in the diagnosis of Systemic Sclerosis (SSc) in adulthood. Although Raynaud’s phenomenon (RP) is very common in childhood, studies on diagnostic methods to differentiate between primary RP (PRP) and secondary RP (SRP) at a young age are scarce. The aim of this study was to determine th...
Article
Objective : The existing literature on mycotic aortic aneurysm is scarce and focuses on treatment. This study evaluates the clinical characteristics, diagnostics, treatment and outcome of patients with a mycotic abdominal aortic aneurysm treated in a tertiary referral center. Methods : A retrospective cohort study was conducted including all patie...
Article
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Background: Serum sulfhydryl groups (R-SH, free thiols) reliably reflect the systemic redox status in health and disease. As oxidation of R-SH occurs rapidly by reactive oxygen species (ROS), oxidative stress is accompanied by reduced levels of free thiols. Oxidative stress has been implicated in the pathophysiology of chronic kidney disease (CKD)...
Article
Background: Although albuminuria is an established risk factor for progression of kidney disease and cardiovascular outcomes, its association with subclinical arterial disease is unclear. [ ¹⁸ F]-sodium fluoride ([ ¹⁸ F]NaF) positron emission tomography (PET) imaging allows detailed early visualization of arterial microcalcification. This study aim...
Article
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The depletion of nitrate and nitrite, stable nitric oxide (NO) end-products, promotes adipose tissue dysfunction and insulin resistance (IR). Dipeptidyl peptidase-4 (DPP-4) inhibitors have the potentially beneficial side effect of increasing NO availability. In this study, nitrate and nitrite levels and the effects of DPP-4 inhibitor linagliptin we...
Article
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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread globally despite the worldwide implementation of preventive measures to combat the disease. Although most COVID-19 cases are characterised by a mild, self-limiting disease course, a considerable subset of patients develop...
Article
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Introduction: Menopause is associated with increased cardiovascular risk, in which oxidative stress plays a pivotal role. Systemic oxidative stress is reflected by decreased levels of free thiols (R-SH, sulfhydryl groups), which are key components of the extracellular antioxidant machinery. In this study, we investigated the relation between serum...
Article
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Aims Non-invasively assessed skin autofluorescence (SAF) measures advanced glycation endproducts (AGEs) in the dermis. SAF correlates with dermal AGEs in Caucasians and Asians, but studies in dark-skinned subjects are lacking. In this pilot we aimed to assess whether SAF signal is representative of intrinsic fluorescence (IF) and AGE accumulation i...
Article
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Purpose2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) uptake is a marker of metabolic activity and is therefore used to measure the inflammatory state of several tissues. This radionuclide marker is transported through the cell membrane via glucose transport proteins (GLUTs). The aim of this study is to investigate whether insulin resistance (IR) or in...
Article
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Background: Serum free thiols (R-SH, sulfhydryl groups) reliably reflect systemic oxidative stress. Since serum free thiols are rapidly oxidized by reactive species, systemic oxidative stress is generally associated with reduced serum free thiol levels. Free thiols associate with favorable disease outcomes in many patient cohorts, and the current...
Article
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Angiotensin‐converting enzyme‐2 (ACE2) has been established as the functional host receptor for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus responsible for the current devastating worldwide pandemic of coronavirus disease 2019 (COVID‐19). ACE2 is abundantly expressed in a variety of cells residing in many different human...
Article
We thank Dr. Lambova for her interesting comment ¹ on our recent article published in The Journal² . We reported that a systemic sclerosis (SSc) or scleroderma-like capillaroscopic pattern is common in patients with Raynaud phenomenon, and can be frequently observed in patients with connective tissue diseases (CTD) other than SSc.
Article
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Objectives: To compare colour duplex ultrasonography (CDU) findings with axillary 18F-fluorodeoxyglucose (FDG) PET/CT findings and to compare the diagnostic performance of temporal and axillary artery CDU with temporal artery CDU alone. Methods: Patients suspected of GCA were retrospectively included. Presence of a halo or occlusion was consider...
Article
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Angiogenic T (Tang) cells are mediators of vascular repair, and characterized by surface expression of CXCR4. This receptor for stromal cell‐derived factor‐1α (SDF‐1α) is cleaved by dipeptidyl peptidase 4 (DPP‐4). Tang cell levels were investigated in people with type 2 diabetes mellitus (T2DM) compared with matched healthy controls (HC) and after...
Article
Background:: Arterial stiffness influences the contour of the digital pressure pulse wave. Method:: Here, we investigated whether the digital pulse propagation index (DPPI), based on the digital pressure pulse wave, DPPI is associated with cardiovascular events, heart failure, and mortality in a large population-based cohort. Between 2001 and 20...
Article
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Oxidative stress plays a pivotal role in the pathogenesis of cardiovascular diseases (CVD). Postmenopausal women have an increased risk of developing CVD due to decreased estrogen availability, which is accompanied by increased oxidative stress. Serum free thiols (R-SH) provide a robust and powerful read-out of systemic oxidative stress. In this st...
Article
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Objective: To assess the minimally invasive single-port thoracoscopic sympathicotomy feasibility and efficacy in patients with treatment-resistant RP. Methods: Single-port thoracoscopic sympathicotomy was performed unilaterally on the left side in eight patients with RP (six males, two females, with a median age of 45.2 years). Five patients had...
Article
Background and aims Type 2 diabetes mellitus (T2DM) is commonly associated with abdominal obesity, predominantly with high visceral adipose tissue (VAT), and is accompanied by premature atherosclerosis. However, the association between VAT and subcutaneous adipose tissue (SAT) with premature atherosclerosis and (i.e. arterial) inflammation is not c...
Conference Paper
Background Systemic sclerosis (SSc) is a progressive fibro-inflammatory autoimmune disease of which the pathogenetic pathways are incompletely understood. Advanced glycation endproducts (AGEs) are oxidative stress derived compounds with potential proinflammatory effects. Their exact role in fibrosis remains unknown. The receptor for AGEs is RAGE, w...
Conference Paper
Background Color duplex ultrasonography (CDU) is recommended as first line of imaging in patients suspected for cranial GCA [1]. However, extra-cranial involvement without temporal artery involvement is found in up to 40% of GCA patients [2]. CDU is very suitable to also assess extra-cranial artery inflammation, of which the axillary artery is rela...
Conference Paper
Background Although several previously conducted studies reported on the prevalence of Raynaud’s phenomenon (RP) in different regions of the world, these studies often included a limited number of selected individuals. Moreover, no studies exist that have systematically assessed the relative contribution of known etiological factors of RP in the ge...
Conference Paper
Background Systemic sclerosis (SSc)-related vasculopathy is generally thought to occur on a microvascular level. However, some observations also suggest involvement of arterial vessels. Macrovascular involvement (e.g., aorta or upper extremity) can be non-invasively assessed by measuring pulse wave velocity (PWV). Although, several studies have ass...
Conference Paper
Background Distinguishing primary Raynaud’s phenomenon (PRP) from Raynaud’s phenomenon secondary to systemic sclerosis (SSc) is crucial in the early detection of SSc. Recently we reported that patients with more severe vasculopathy suffer from a prolonged ischemia time during Raynaud’s attack. [1] additionally, it appears that the thumb is more fre...
Conference Paper
Background Pulmonary involvement in systemic sclerosis (SSc) is very difficult to treat when diagnosed too late. Therefore, in order to optimally use “the window of opportunity” more attention should be given to the early identification of SSc. To the best of our knowledge, no studies exist that have structurally assessed the epidemiology of red fl...
Conference Paper
Background In some patients, Raynaud’s Phenomenon (RP) symptoms prove resistant to conventional vasodilatory treatment. Thoracic sympathectomy is shown to be effective as treatment of RP, but is associated with surgical burden. During this procedure, the sympathetic nerve traversing to the upper extremity is dissected, subsequently leading to vasod...
Article
Full-text available
Raynaud's phenomenon (RP) is often the first sign of systemic sclerosis (SSc). Molecular mechanisms involved are incompletely understood, but reactive oxygen, nitrogen, and sulfur species are thought to play an important role in the pathogenesis of SSc. Free thiol groups play a protective role against oxidative stress and may represent an attractiv...
Article
Objective To assess the presence of a systemic sclerosis (SSc) pattern on nailfold capillary microscopy (NCM) in patients with Raynaud phenomenon (RP) and to explore its association with abnormal pulmonary function tests (PFT). Methods NCM patterns were assessed in 759 consecutive patients with RP. Patterns were classified as normal (n = 354), non...
Article
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Background: 18F-NaF positron emission tomography (PET) targets microcalcifications. We compared in vitro microPET assessed 18F-NaF uptake between culprit and non-culprit human carotid plaques. Furthermore, we compared 18F-NaF uptake with calcification visualized on microcomputed tomography (microCT). Methods: Carotid plaques from stroke patients...
Article
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Purpose: Severity of abdominal obesity and possibly levels of metabolic activity of abdominal visceral adipose tissue (VAT) are associated with an increased risk for cardiovascular disease (CVD). In this context, the purpose of the current study was to evaluate the reproducibility and repeatability of a semi-automated method for assessment of the...
Article
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Background The challenge of the primary prevention of cardiovascular disease (CVD) is to identify patients who would benefit from treatment with statins. Statins are currently prescribed to many patients, even those at a low 10-year risk of CVD. These latter patients may not be eligible for statins according to current guidelines. Design This stud...
Article
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Purpose Advanced glycation endproducts (AGEs) and their precursors α-dicarbonyls are implicated in the progression of diabetic retinopathy. The purpose of this study was to assess AGEs and α-dicarbonyls in the vitreous of patients with type 2 diabetes mellitus (T2DM) with early stages or absence of diabetic retinopathy. Methods We examined vitreou...
Article
Dipeptidyl peptidase (DPP)-4 inhibitors are a class of oral antidiabetic agents of which favorable cardiovascular effects are suggested. For example, experimental studies have shown that DPP4-inhibitors reduce atherosclerotic plaque area and macrophage accumulation [(1)][1]. However, there are no
Article
Aims: To evaluate the effects of the DPP-4 inhibitor linagliptin on aortic pulse wave velocity (PWV) as a surrogate marker of arterial stiffness and early atherosclerosis in early type 2 diabetes subjects. Materials and methods: A total of 45 type 2 diabetes subjects (median age 63 (IQR: 54-66) years, 61% male, mean hemoglobinA1c (HbA1c ) 6.3 ±...
Article
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Purpose: Advanced glycation endproducts (AGEs) have been suggested to play a role in retinal redetachment by promoting proliferative vitreoretinopathy (PVR). The purpose of this study was to investigate whether AGEs, in combination with other clinical characteristics, were able to identify patients at high risk for redetachment after vitrectomy fo...
Article
Introduction: Dipeptidyl peptidase (DPP)-4 inhibitors are a class of oral antidiabetic drugs. Recent experimental studies have suggested beneficial vascular effects, but clinical evidence is limited. Hypothesis: The primary objective was to evaluate the effects of the DPP-4 inhibitor linagliptin on aortic pulse wave velocity (PWV) as a measure of a...
Article
The metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease. The aim of this study is to determine the influence of MetS on short- and long-term outcome and survival after carotid endarterectomy (CEA). Between January 2005 and December 2014, data from all patients undergoing CEA were prospectively recorded. The metabolic s...
Article
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Background: Advanced glycation end products (AGEs) have been implicated in multiple organ failure, predominantly via their cellular receptor (RAGE) in preclinical studies. Little is known about the time course and prognostic relevance of AGEs in critically ill human patients, including those with severe sepsis. Objective: 1) To explore the relia...
Article
Objective: Type 2 diabetes is accompanied by premature atherosclerosis and arterial stiffness. The underlying association remains incompletely understood. The possible relationship between subclinical arterial inflammation assessed by (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and arterial stiffness wa...
Article
Objective: The aim of the study was to assess the association between plethysmographically measured vasospasms during stepwise cooling and recovery, as an index for digital ischaemia, and nailfold capillaroscopic pattern (NCP) severity in patients with primary or secondary RP, including SSc. Methods: In 381 consecutive patients with suspected RP...
Article
Patients with peripheral artery disease are at risk for critical limb ischemia and amputation. Accumulation of advanced glycation end products is increased and predictive for coronary and cerebrovascular events in several high cardiovascular risk groups. We hypothesized that accumulation of tissue advanced glycation end products, measured by skin a...
Article
Glucagon-like peptide-1 receptor agonists (GLP-1 RA) added to insulin in type 2 diabetes (T2DM) patients reduces HbA1c, total daily insulin dose (TDD), and body weight in short term studies (1-12 months). We evaluated these GLP-1 RA effects in a prospective real life cohort study of overweight T2DM patients on insulin after 6 weeks, 3, 6, 9, 12, 18...
Article
Advanced glycation end products play a pivotal role in atherosclerosis. Recently, we showed that tissue advanced glycation end products deposition, noninvasively assessed by skin autofluorescence (SAF), is increased in patients with peripheral artery disease. The aim of the present study was to establish whether SAF is associated with all-cause mor...
Article
Full-text available
Advanced glycation endproducts (AGEs) may be involved in the development of atherosclerosis, beyond diabetes and renal disease. Skin autofluorescence (AF) is a non-invasive marker for AGEs. We examined whether skin AF is increased in (subclinical) atherosclerosis and associated with the degree of atherosclerosis independent of diabetes and renal fu...
Conference Paper
PURPOSE Studies in diabetes and renal disease patients show that advanced glycation endproducts (AGEs) may be linked to the development of atherosclerosis. AGE levels can be measured non-invasively by skin autofluorescence (AF). It is not yet known if skin AF is already increased in subclinical atherosclerosis. The purpose of this study was to eval...
Article
Objective: Evidence for an important role of advanced glycation end products (AGEs) in the development of atherosclerosis and cardiovascular disease beyond diabetes mellitus and renal disease is growing. Skin autofluorescence (SAF) is a validated noninvasive measure of tissue AGEs. We hypothesized that SAF is elevated in peripheral artery disease...
Article
High density lipoprotein (HDL) particles protect apolipoprotein B-containing lipoproteins from oxidative modification. An impaired anti-oxidative functionality of HDL in type 2 diabetes mellitus (T2DM) may contribute to enhanced formation of oxidative stress products, such as Advanced Glycation Endproducts (AGEs). We tested whether in T2DM the HDL...
Article
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Latitude is an important determinant of C-IMT, which is not explained by between-country differences in established VRFs. Other unknown contributory mechanisms such as heritable, nutritional, or environmental factors may be important in the genesis of this geographical gradient.