Richard G Ijzerman

VU University Medical Center, Amsterdamo, North Holland, Netherlands

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Publications (63)298.84 Total impact

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    ABSTRACT: Gut-derived hormones, such as glucagon-like peptide-1 (GLP-1), have been proposed to relay information to the brain to regulate appetite. GLP-1 receptor agonists, currently used for the treatment of type 2 diabetes (T2DM), improve glycemic control and stimulate satiety leading to decreases in food intake and bodyweight. We hypothesized that food intake reduction following GLP-1 receptor activation is mediated through appetite- and reward-related brain areas. Obese T2DM patients, normoglycemic obese and lean individuals (n=48) were studied in a randomized, crossover, placebo-controlled trial. Using functional MRI we determined the acute effects of intravenous administration of the GLP-1 receptor agonist exenatide, with or without prior GLP-1 receptor blockade using exendin9-39, on brain responses to food pictures, during a somatostatin pancreatic-pituitary clamp. Obese T2DM patients and normoglycemic obese vs. lean subjects showed increased brain responses to food pictures in appetite- and reward-related brain regions (insula and amygdala). Exenatide vs. placebo decreased food intake and food-related brain responses in T2DM patients and obese subjects (in insula, amygdala, putamen and orbitofrontal cortex). These effects were largely blocked by prior GLP-1 receptor blockade using exendin9-39. Our findings provide novel insights into the mechanisms by which GLP-1 regulates food intake and how GLP-1 receptor agonists cause weight loss.
    Diabetes 07/2014; · 7.90 Impact Factor
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    ABSTRACT: Patients with longstanding type 1 diabetes may develop microangiopathy due to high cumulative glucose exposure. Also, chronic hyperglycemia is related to cerebral alterations and cognitive dysfunction. Whether the presence of microangiopathy is conditional to the development of hyperglycemia-related cerebral compromise is unclear. Since subcortical, rather than cortical, volume loss was previously related to cognitive dysfunction in other populations, we measured these brain correlates and cognitive functions in patients with longstanding type 1 diabetes with and without microangiopathy.RESEARCH DESIGN AND METHODS: We evaluated differences in subcortical volume and cortical thickness and volume in type 1 diabetic patients with (n = 51) and without (n = 53) proliferative retinopathy and 49 control subjects and related volume differences to cognitive dysfunction. Analyses were corrected for age, sex, systolic blood pressure, and A1C.RESULTS: Putamen and right thalamic volume loss was noted in both patients with and without proliferative retinopathy compared with control subjects (all P < 0.05). Additionally, in patients with proliferative retinopathy relative to control subjects, volume loss of the bilateral nucleus accumbens was found (all P < 0.05). No differences were observed between the two patient groups. Cortical thickness and volume were not different between groups. In pooled analyses, lower left nucleus accumbens volume was associated with cognitive dysfunction (P < 0.035).CONCLUSIONS: This study shows subcortical, but not cortical, volume loss in relation to cognitive dysfunction in patients with long-standing type 1 diabetes, irrespective of microangiopathy. The time-course, pathophysiology, and clinical relevance of these findings need to be established in longitudinal and mechanistic studies.
    Diabetes care. 06/2014;
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    ABSTRACT: Type 1 diabetes mellitus (T1DM) is associated with cerebral compromise, typically found in patients with microangiopathy. Associations between subclinical macroangiopathy and the brain, whether or not in the presence of microangiopathy, have not been fully explored in T1DM. We hypothesized that subclinical macroangiopathy in adult T1DM may affect the brain and interacts with microangiopathy. In 51 asymptomatic T1DM patients with, 53 without proliferative retinopathy and 51 controls, right common carotid artery ultrasound was used to assess intima media thickness (cIMT) and distensibility (cD). Neuropsychological tests for cognitive functions, and magnetic resonance imagining for white matter integrity and functional connectivity, i.e. neuronal communication, were used. After correction for confounders, cIMT was borderline significantly increased in all T1DM patients (P = 0.071), whereas cD was not statistically significantly altered (P = 0.45). Patients with proliferative retinopathy showed the largest increase in cIMT and decrease in cD. In all participants, after adjustment for confounders, increased cIMT was related to decreased white matter integrity (beta = -0.198 P = 0.041) and decreased functional connectivity in visual areas (beta = -0.195 P = 0.046). For cognition, there was a significant interaction between cIMT and the presence of proliferative retinopathy after adjustment for confounding factors (all P < 0.05). Increased cIMT was associated with lower general cognitive ability (beta = -0.334; P = 0.018), information processing speed (beta = -0.361; P = 0.010) and attention (beta = -0.394; P = 0.005) scores in patients without, but not in patients with proliferative retinopathy. These findings suggest that subclinical macroangiopathy may be a factor in the development of diabetes-related cognitive changes in uncomplicated T1DM, whereas in patients with advanced T1DM, proliferative retinopathy may rather be the driving force of cerebral compromise.
    Cardiovascular Diabetology 03/2014; 13(1):58. · 4.21 Impact Factor
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    ABSTRACT: Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF) insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli. ClinicalTrials.gov NCT00626080.
    PLoS ONE 01/2014; 9(4):e94483. · 3.53 Impact Factor
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    ABSTRACT: The delivery of nutrients to the gastrointestinal tract after food ingestion activates the secretion of several gut-derived mediators, including the incretin hormone glucagon-like peptide-1 (GLP-1). GLP-1 receptor agonists (GLP-1RA), such as exenatide and liraglutide, are currently successfully employed in the treatment of patients with type 2 diabetes. GLP-1RA improve glycaemic control and stimulate satiety leading to reductions in food intake and body weight. Besides gastric distension and peripheral vagal nerve activation, GLP-1RA induce satiety by influencing brain regions involved in the regulation of feeding, and several routes of action have been proposed. This review summarizes the evidence for a physiological role of GLP-1 in the central regulation of feeding behaviour and the different routes of action involved. Also, we provide an overview of presently available data on pharmacological stimulation of GLP-1 pathways leading to alterations in CNS activity, reductions in food intake and weight loss.
    Journal of Endocrinology 12/2013; · 4.06 Impact Factor
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    ABSTRACT: Objective To investigate whether proliferative diabetic retinopathy in type 1 diabetes patients can be generalized to cerebral small vessel disease, and is associated with impaired peripheral microvascular function.Research design and Methods Thirty-three patients with proliferative diabetic retinopathy (PDR+), 34 patients without retinopathy (PDR-) and 33 controls underwent MRI to assess cerebral microangiopathy (cerebral microbleeds) and ischemic damage (white matter hyperintensities and lacunes). Peripheral microvascular function, i.e. skin capillary density and capillary recruitment, was assessed by capillary microscopy.ResultsCerebral microbleeds, but not ischemic damage, were more prevalent in PDR+ patients versus the other groups (P<0.05). A trend was found across groups for the lowest baseline capillary density in PDR+ patients (P-for-trend=0.05). In individuals with microbleeds capillary recruitment was impaired compared to those without microbleeds (P=0.04).Conclusions In PDR+ patients cerebral microbleeds prevalence was higher and seems part of generalized microangiopathy that may affect the skin and the brain.
    Diabetes care 12/2013; · 7.74 Impact Factor
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    ABSTRACT: To compare cerebral blood flow (CBF) values measured using magnetic resonance imaging (MRI) arterial spin labeling (ASL) with those obtained with [(15) O]H2 O positron emission tomography (PET), the gold standard for measuring CBF in vivo. Data were collected in 11 healthy men and in 20 age- and body mass index (BMI)-matched type 1 diabetic men. Pseudo-continuous ASL (PCASL) data were acquired at 3 T and [(15) O]H2 O PET scans were acquired using a high-resolution PET scanner. Input functions were obtained using on-line arterial blood sampling. Whole brain and regional CBF values were compared. For both modalities, whole brain CBF was similar in both subject groups. In groups combined, average whole brain CBF was 0.30 ± 0.05 mL·cm(-3) ·min(-1) for [(15) O]H2 O PET and 0.34 ± 0.05 mL·cm(-3) ·min(-1) for ASL MRI (P < 0.01). A significant correlation between methods was observed for whole brain, gray and white matter. In 12 out of 33 brain regions a significant difference between methods was observed. PCASL provides CBF values that correlate with [(15) O]H2 O PET-derived values, but is less accurate. PCASL may be an attractive alternative when absolute quantification is not needed.J. Magn. Reson. Imaging 2013. © 2013 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 11/2013; · 2.57 Impact Factor
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    ABSTRACT: OBJECTIVE To test the hypothesis that insulin detemir, which is associated with less weight gain than other basal insulin formulations, exerts its weight modulating effects by acting on brain regions involved in appetite regulation, as represented by altered cerebral blood flow (CBF) or cerebral glucose metabolism (CMRglu).RESEARCH DESIGN AND METHODS Twenty-eight male type 1 diabetic patients (age 36.9 ± 9.7 years, BMI 24.9 ± 2.7 kg/m(2), A1C 7.5 ± 0.6%) successfully completed a randomized crossover study, consisting of two periods of 12-week treatment with either insulin detemir or NPH insulin, both in combination with prandial insulin aspart. After each treatment period, patients underwent positron emission tomography scans to measure regional CBF and CMRglu.RESULTSAfter 12 weeks, A1C, daily insulin doses, fasting insulin, and blood glucose levels were similar between treatments. Insulin detemir resulted in body weight loss, whereas NPH insulin induced weight gain (between-treatment difference 1.3 kg; P = 0.02). After treatment with insulin detemir relative to NPH insulin, CBF was higher in brain regions involved in appetite regulation, whereas no significant difference in CMRglu was observed.CONCLUSIONS Treatment with insulin detemir versus NPH insulin resulted in weight loss, paralleled by increased CBF in appetite-related brain regions in the resting state, in men with well-controlled type 1 diabetes. These findings lend support to the hypothesis that a differential effect on the brain may contribute to the consistently observed weight-sparing effect of insulin detemir.
    Diabetes care 10/2013; · 7.74 Impact Factor
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    ABSTRACT: Glucocorticoids (GCs) are widely used anti-inflammatory agents that frequently induce side effects, including insulin resistance, diabetes and hypertension. Here, we investigated the contribution of microvascular dysfunction to the development of these adverse effects in healthy men. In a randomised, placebo-controlled, dose-response intervention study, 32 healthy normoglycaemic men (age: 21 ± 2 years; BMI: 21.9 ± 1.7 kg/m(2)) were allocated to receive prednisolone 30 mg once daily (n = 12), prednisolone 7.5 mg once daily (n = 12) or placebo (n = 8) for 2 weeks using block randomisation. A central office performed the treatment allocation, and medication was dispersed by the hospital pharmacy that was also blinded. Treatment allocation was kept in concealed envelopes. Participants, study personnel conducting the measures and assessing the outcome were blinded to group assignment. The study was conducted at a university hospital. Primary endpoint was prednisolone-induced changes in microvascular function, which was assessed by capillary microscopy. Insulin sensitivity was determined by hyperinsulinaemic-euglycaemic clamp and postprandial glycaemic excursions by standardised meal tests. Compared with placebo, prednisolone 7.5 mg and 30 mg decreased insulin-stimulated capillary recruitment by 9 ± 4% and 17 ± 3%, respectively (p < 0.01). In addition, prednisolone 7.5 mg and 30 mg reduced insulin sensitivity (M value) by -11.4 ± 4.5 μmol kg(-1) min(-1) and -25.1 ± 4.1 μmol kg(-1) min(-1) (p < 0.001) and increased postprandial glucose levels by 11 ± 5% and 27 ± 9% (p < 0.001), respectively. Only high-dose prednisolone increased systolic blood pressure (6 ± 1.2 mmHg, p = 0.006). Prednisolone-induced changes in insulin-stimulated capillary recruitment were associated with insulin sensitivity (r = +0.76; p < 0.001), postprandial glucose concentrations (r = -0.52; p < 0.03) and systolic blood pressure (r = -0.62; p < 0.001). Prednisolone increased resistin concentrations, which were negatively related to insulin-stimulated capillary recruitment (r = -0.40; p = 0.03). No effects were noted on adiponectin and leptin concentrations. Prednisolone treatment was well tolerated; none of the participants left the study. Prednisolone-induced impairment of insulin-stimulated capillary recruitment was paralleled by insulin resistance, increased postprandial glucose levels, hypertension and increased circulating resistin concentrations in healthy men. We propose that GC-induced impairments of microvascular function may contribute to the adverse effects of GC treatment on glucose metabolism and blood pressure. isrctn.org ISRTCN 78149983 FUNDING: The study was funded by the Dutch Top Institute Pharma T1-106.
    Diabetologia 08/2013; · 6.49 Impact Factor
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    ABSTRACT: Subclinical systemic microvascular dysfunction exists already in asymptomatic patients with type 1 diabetes. We hypothesized that microangiopathy, resulting from long-standing systemic hyperglycemia and hyperinsulinemia, may be generalized to the brain, resulting in changes in cerebral blood flow and metabolism in these patients. We performed dynamic [(15)O]H2O and [(18)F]-fluoro-2-deoxy-D-glucose ([(18)F]FDG) brain positron emission tomography (PET) scans to measure cerebral blood flow (CBF) and cerebral glucose metabolism (CMRglu), respectively, in 30 type 1 diabetic patients and 12 age-matched healthy controls after an overnight fast. Regions of interest were automatically delineated on co-registered MRI images and full kinetic analysis was performed. Plasma glucose and insulin levels were higher in patients versus controls. Total grey matter CBF was 9%, whereas CMRglu was 21% lower in type 1 diabetic versus control subjects. We conclude that at real-life fasting glucose and insulin levels, type 1 diabetes is associated with decreased resting cerebral glucose metabolism, that is only partially explained by the decreased CBF. These findings suggest that other mechanisms than generalized microangiopathy account for the altered CMRglu observed in well-controlled type 1 diabetes. (NCT00626080).
    Diabetes 03/2013; · 7.90 Impact Factor
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    ABSTRACT: AIMS/HYPOTHESIS: We examined the effects of serum insulin levels on vagal control over the heart and tested the hypothesis that higher fasting insulin levels are associated with lower vagal control. We also examined whether experimentally induced increases in insulin by beta cell secretagogues, including glucagon-like peptide-1 (GLP-1), will decrease vagal control. METHODS: Respiration and ECGs were recorded for 130 healthy participants undergoing clamps. Three variables of cardiac vagal effects (the root mean square of successive differences [rMSSD] in the interbeat interval of the heart rate [IBI], heart-rate variability [HRV] caused by peak-valley respiratory sinus arrhythmia [pvRSA], and high-frequency power [HF]) and heart rate (HR) were obtained at seven time points during the clamps, characterised by increasing levels of insulin (achieved by administering insulin plus glucose, glucose only, glucose and GLP-1, and glucose and GLP-1 combined with arginine). RESULTS: Serum insulin level was positively associated with HR at all time points during the clamps except the first-phase hyperglycaemic clamp. Insulin levels were negatively correlated with variables of vagal control, reaching significance for rMSSD and log(10)HF, but not for pvRSA, during the last four phases of the hyperglycaemic clamp (hyperglycaemic second phase, GLP-1 first and second phases, and arginine). These associations disappeared when adjusted for age, BMI and insulin sensitivity. Administration of the beta cell secretagogues GLP-1 and arginine led to a significant increase in HR, but this was not paired with a significant reduction in HRV measures. CONCLUSION/INTERPRETATION: Experimentally induced hyperinsulinaemia is not correlated with cardiac vagal control or HR when adjusting for age, BMI and insulin sensitivity index. Our findings suggest that exposure to a GLP-1 during hyperglycaemia leads to a small acute increase in HR but not to an acute decrease in cardiac vagal control.
    Diabetologia 02/2013; · 6.49 Impact Factor
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    ABSTRACT: BACKGROUND: Positron emission tomography (PET) allows for the measurement of cerebral blood flow (CBF; based on [15O]H2O) and cerebral metabolic rate of glucose utilization (CMRglu; based on [18 F]-2-fluoro-2-deoxy-d-glucose ([18 F]FDG)). By using kinetic modeling, quantitative CBF and CMRglu values can be obtained. However, hardware limitations led to the development of semiquantitive calculation schemes which are still widely used. In this paper, the analysis of CMRglu and CBF scans, acquired on a current state-of-the-art PET brain scanner, is presented. In particular, the correspondence between nonlinear as well as linearized methods for the determination of CBF and CMRglu is investigated. As a further step towards widespread clinical applicability, the use of an image-derived input function (IDIF) is investigated. METHODS: Thirteen healthy male volunteers were included in this study. Each subject had one scanning session in the fasting state, consisting of a dynamic [15O]H2O scan and a dynamic [18 F]FDG PET scan, acquired at a high-resolution research tomograph. Time-activity curves (TACs) were generated for automatically delineated and for manually drawn gray matter (GM) and white matter regions. Input functions were derived using on-line arterial blood sampling (blood sampler input function (BSIF)). Additionally, the possibility of using carotid artery IDIFs was investigated. Data were analyzed using nonlinear regression (NLR) of regional TACs and parametric methods. RESULTS: After quality control, 9 CMRglu and 11 CBF scans were available for analysis. Average GM CMRglu values were 0.33 +/- 0.04 mumol/cm3 per minute, and average CBF values were 0.43 +/- 0.09 mL/cm3 per minute. Good correlation between NLR and parametric CMRglu measurements was obtained as well as between NLR and parametric CBF values. For CMRglu Patlak linearization, BSIF and IDIF derived results were similar. The use of an IDIF, however, did not provide reliable CBF estimates. CONCLUSION: Nonlinear regression analysis, allowing for the derivation of regional CBF and CMRglu values, can be applied to data acquired with high-spatial resolution current state-of-the-art PET brain scanners. Linearized models, applied to the voxel level, resulted in comparable values. CMRglu measurements do not require invasive arterial sampling to define the input function.Trial registrationClinicalTrials.gov NCT00626080.
    EJNMMI research. 11/2012; 2(1):63.
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    Diabetologia 04/2012; 55(4):1218-20. · 6.49 Impact Factor
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    ABSTRACT: Cognitive functioning depends on intact brain networks that can be assessed with functional magnetic resonance imaging (fMRI) techniques. We hypothesized that cognitive decrements in type 1 diabetes mellitus (T1DM) are associated with alterations in resting-state neural connectivity and that these changes vary according to the degree of microangiopathy. T1DM patients with (MA(+): n = 49) and without (MA(-): n = 52) microangiopathy were compared with 48 healthy control subjects. All completed a neuropsychological assessment and resting-state fMRI. Networks were identified using multisubject independent component analysis; specific group differences within each network were analyzed using the dual-regression method, corrected for confounding factors and multiple comparisons. Relative to control subjects, MA(-) patients showed increased connectivity in networks involved in motor and visual processes, whereas MA(+) patients showed decreased connectivity in networks involving attention, working memory, auditory and language processing, and motor and visual processes. Better information-processing speed and general cognitive ability were related to increased degree of connectivity. T1DM is associated with a functional reorganization of neural networks that varies, dependent on the presence or absence of microangiopathy.
    Diabetes 03/2012; 61(7):1814-21. · 7.90 Impact Factor
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    ABSTRACT: Insulin resistance, i.e. impaired insulin-mediated glucose uptake (IMGU), is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). Insulin-induced capillary recruitment (IICR) is considered a significant determinant of IMGU. We investigated whether IICR is a determinant IMGU in obese and lean women with and without PCOS. The study included 36 women with PCOS (20 lean, BMI 21.9 ± 2.3 kg/m(2) and 16 obese, BMI 35.9 ± 6.0 kg/m(2)) and 27 age-matched healthy controls (14 lean, BMI 22.2 ± 1.8 kg/m(2) and 13 obese, BMI 40.5 ± 7.0 kg/m(2)). IICR was evaluated by capillary microscopy during an isoglycemic-hyperinsulinemic clamp. IMGU was expressed as M/I value. The M/I value was significantly lower in obese PCOS women compared with obese controls [0.5 (0.2-1.1) versus 0.8 (0.3-1.4) (mg kg(-1) min(-1) pmol l(-1)) × 100, P < 0.01], whereas the small difference between lean PCOS and lean control women was non-significant [1.5 (0.5-2.6) versus 1.7 (1.0-3.7) (mg kg(-1) min(-1) pmol l(-1)) × 100, P = 0.17]. Hyperinsulinemia increased capillary recruitment in lean controls (53.5 ± 20.3 versus 64.9 ± 27.4 n/mm(2), P < 0.05), but not in either PCOS group nor in obese controls. IICR and androgens were a determinant of M/I value only in lean women with or without PCOS. PCOS per se is associated with impaired IICR. Obese women with PCOS, in part independent of obesity, demonstrated a profound insulin resistance, whereas the difference between lean PCOS women and healthy controls was small and statistically non-significant. IICR was a determinant of IMGU in lean, but not in obese, women regardless of the presence of PCOS.
    Human Reproduction 09/2011; 26(11):3130-7. · 4.67 Impact Factor
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    ABSTRACT: Individuals with impaired glucose metabolism (IGM) are at high risk of developing type 2 diabetes (T2DM). The renin-angiotensin system (RAS) is activated in insulin-resistant states and its inhibition resulted in delayed onset of T2DM. The underlying mechanisms may include improvement in microvascular structure and function, which may increase glucose and insulin delivery to insulin-sensitive tissues. We hypothesized that functional and structural capillary density is impaired in insulin-resistant individuals with IGM and that treatment with the angiotensin-receptor blocker valsartan (VAL) will improve insulin sensitivity and microvascular function. In this randomized controlled trial, individuals with IGM (n = 48) underwent a hyperinsulinaemic-euglycaemic clamp to assess insulin sensitivity (M-value) and capillaroscopy to examine baseline skin capillary density (BCD), capillary density after arterial occlusion (PRH) and capillary density during venous occlusion (VEN) before and after 26 weeks of VAL or placebo (PLB). Sixteen BMI-matched individuals with normal glucose metabolism (NGM) served as controls. Individuals with IGM were more insulin resistant (P < 0.001) and had impaired microvascular function compared with those with NGM (all P < 0.01). Univariate associations were found for microvascular function (BCD, PRH, VEN) and M-value (all P < 0.005). The relations were independent of age, sex and BMI. VAL improved insulin sensitivity (P = 0.034) and lowered blood pressure as compared with PLB, whereas microvascular function remained unchanged. In insulin-resistant individuals with IGM, impaired functional and structural capillary density was inversely associated with insulin sensitivity. VAL improved insulin sensitivity without affecting the functional and structural capillary density, indicating that other mechanisms may be stronger determinants in the VAL-mediated insulin-sensitizing effect.
    Journal of Hypertension 08/2011; 29(10):1955-62. · 4.22 Impact Factor
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    ABSTRACT: Right ventricular dilatation in the setting of acute pulmonary embolism is associated with an adverse prognosis. Treatment with a pulmonary vasodilator has never been studied systematically. We evaluated the effect of epoprostenol on right ventricular diameter and function in patients with acute pulmonary embolism and right ventricular dilatation. In a randomized, single-blind study, 14 patients with acute pulmonary embolism received epoprostenol or placebo infusion for 24 hours on top of conventional treatment. Effects on right ventricular end-diastolic diameter, systolic pulmonary artery pressure, right ventricle fractional area change and tricuspid annular plane systolic excursion were assessed by serial echocardiography. Furthermore Troponin T and NT-proBNP were measured serially. Compared to placebo, epoprostenol was associated with a relative change from baseline in right ventricular end-diastolic diameter of +2% after 2.5 hours and -8% after 24 hours. Epoprostenol did not have a significant effect on systolic pulmonary artery pressure, right ventricular fractional area change and tricuspid annular plane systolic excursion, nor on biochemical parameters. In patients with acute pulmonary embolism and right ventricular overload, treatment with epoprostenol did not improve right ventricular dilatation or any other measured variables of right ventricular overload. Registration: URL: NCT01014156Medical ethical committee: Medisch-ethische toetsingscommissie (METc) from the VUmc (free university medical centre).
    BMC Pulmonary Medicine 03/2010; 10:18. · 2.76 Impact Factor
  • Annals of Clinical Biochemistry 04/2009; 46(Pt 3):263-4. · 1.92 Impact Factor
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    ABSTRACT: Based on fasting insulin and glucose, several indices of insulin sensitivity have been developed in adults. Recently, it has been demonstrated that incorporation of the fasting free fatty acid (FFA) concentration improves the association with insulin sensitivity in adults. We investigated the association of clamp-derived insulin sensitivity with indices of insulin sensitivity derived from fasting blood in prepubertal children and adults, with and without incorporation of FFAs. We studied 59 healthy adults and 29 of them are prepubertal children. We measured insulin sensitivity with the euglycemic-hyperinsulinemic clamp. Based on fasting insulin and glucose, we estimated insulin sensitivity with the homeostasis model assessment (HOMA), the quantitative insulin sensitivity check index (QUICKI), and the revised QUICKI after the incorporation of FFAs. The associations of HOMA and QUICKI with clamp-derived insulin sensitivity in children (r=-0.55 and 0.54 respectively; P<0.01) were similar to those in adults (r=-0.54 and 0.53 respectively; P<0.01). However, incorporation of FFAs into the QUICKI model resulted in an increase in the association in adults, but not in children (r=0.68 and 0.48 respectively; P<0.01). Adding FFA levels to a regression model with glucose and insulin as independent variables resulted in an increase in the explained variance in clamp-derived insulin sensitivity in adults, but not in children (P value 0.004 in adults and 0.3 in children). HOMA and QUICKI are associated with clamp-derived insulin sensitivity in both children and adults. Incorporating fasting levels of FFAs into the QUICKI model improves the association with clamp-derived insulin sensitivity in adults, but not in children.
    European Journal of Endocrinology 10/2008; 160(1):59-64. · 3.14 Impact Factor
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    Richard G Ijzerman, Renate T de Jongh, Erik H Serné
    Journal of Applied Physiology 07/2008; 105(1):378; author reply 389. · 3.48 Impact Factor

Publication Stats

1k Citations
298.84 Total Impact Points

Institutions

  • 2003–2014
    • VU University Medical Center
      • Department of Internal Medicine
      Amsterdamo, North Holland, Netherlands
  • 2000–2008
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Department of Internal Medicine
      • • Department of Medicine
      Amsterdam, North Holland, Netherlands
  • 2001–2006
    • VU University Amsterdam
      • • Department of Biological Psychology
      • • Institute for Cardiovascular Research VU
      Amsterdamo, North Holland, Netherlands