Cardiovascular risk assessment in diabetes

Research described in this thesis is based on clinical data obtained through diabetes cardiovascular risk management (DIACARM) project. A clinical protocol founded on the co-operation of the departments of endocrinology, cardiology, nephrology, radiology and nuclear medicine at the Leiden University Medical Center. This protocol is set to improve medical care at patient and provide more insight into cardiovascular risk stratification in asymptomatic patients with diabetes. The first part of the thesis focuses on the nature of coronary artery disease in diabetes, and its presentation with different imaging modalities. The relation between epicardial adipose tissue and plasma biomarkers with coronary atherosclerosis were investigated. Furthermore, extent and morphology of atherosclerosis are compared in patients with type 1- and type 2 diabetes. In the second part of the thesis the value of non-invasive vascular measurements (carotid intima media thickness, pulse wave velocity) and cardiac imaging techniques were evaluated and compared for risk stratification of coronary artery disease in diabetes. The final part of the thesis describes a novel technique, sidestream dark field imaging, for the assessment of the microcirculation at capillary level. Parameters of microcirculation were shown to have a relation with coronary artery disease in diabetesUBL - phd migration 201

Changes in labial capillary density on ascent to and descent from high altitude

Present knowledge of how the microcirculation is altered by prolonged exposure to hypoxia at high altitude is incomplete and modification of existing analytical techniques may improve our knowledge considerably. We set out to use a novel simplified method of measuring in vivo capillary density during an expedition to high altitude using a CytoCam incident dark field imaging video-microscope. The simplified method of data capture involved recording one-second images of the mucosal surface of the inner lip to reveal data about microvasculature density in ten individuals. This was done on ascent to, and descent from, high altitude. Analysis was conducted offline by two independent investigators blinded to the participant identity, testing conditions and the imaging site. Additionally we monitored haemoglobin concentration and haematocrit data to see if we could support or refute mechanisms of altered density relating to vessel recruitment. Repeated sets of paired values were compared using Kruskall Wallis Analysis of Variance tests, whilst comparisons of values between sites was by related samples Wilcoxon Signed Rank Test. Correlation between different variables was performed using Spearman’s rank correlation coefficient, and concordance between analysing investigators using intra-class correlation coefficient. There was a significant increase in capillary density from London on ascent to high altitude; median capillaries per field of view area increased from 22.8 to 25.3 (p=0.021). There was a further increase in vessel density during the six weeks spent at altitude (25.3 to 32.5, p=0.017). Moreover, vessel density remained high on descent to Kathmandu (31.0 capillaries per field of view area), despite a significant decrease in haemoglobin concentration and haematocrit. Using a simplified technique, we have demonstrated an increase in capillary density on early and sustained exposure to hypobaric hypoxia at thigh altitude, and that this remains elevated on descent to normoxia. The technique is simple, reliable and reproducible

CT angiography; useful in non-selected outpatients?

Dance has been a part of the physical education (PE) curriculum in several countries for a longtime. In spite of this, studies demonstrate that the position of dance in the subject of PE iscontested and that little time is devoted to dance. The overall aim of this article is to examine theposition of dance as a pedagogical discourse in Swedish steering documents over time. Theempirical material consists of five Swedish curricula for PE over a period of 50 years (1962–2011).Discourse analysis is used to identify organised systems of meaning, including privileged andprioritised values. Our theoretical frame of reference draws on Bernstein’s concept of codes. Threedifferent knowledge areas within dance are found in the text material: ‘dance as cultural preserver’,‘dance as bodily exercise’ and ‘dance as expression’. Three pedagogical discourses emerge fromthese knowledge areas: an identity formation discourse, a public health discourse and an aestheticdiscourse. The identity formation discourse in earlier curricula focuses on the perpetuation ofSwedish and Nordic cultural traditions, while in later curricula, it emphasises the construction of abroader multicultural identity formation related to the understanding of different cultures. Thepublic health discourse constitutes a prioritised understanding of dance as physical training relatedto a healthy lifestyle. The aesthetic discourse, which has the weakest position over time, representsthe valuing of embodied experiences and feelings expressed through movements. This discourse isclosely linked to the construction of gender. Over time, a new performance code came to surpassthe former competence code in the steering documents. The performance code positions dance inPE as mainly a physical activity with little artistic or aesthetic value. The pedagogical discourse ofdance remains within a highly disciplinary framework of social control

The Transcriptome of Human Epicardial, Mediastinal and Subcutaneous Adipose Tissues in Men with Coronary Artery Disease

The biological functions of epicardial adipose tissue (EAT) remain largely unknown. However, the proximity of EAT to the coronary arteries suggests a role in the pathogenesis of coronary artery disease (CAD). The objectives of this study were to identify genes differentially regulated among three adipose tissues, namely EAT, mediastinal (MAT) and subcutaneous (SAT) and to study their possible relationships with the development of cardiovascular diseases.Samples were collected from subjects undergoing coronary artery bypass grafting surgeries. Gene expression was evaluated in the three adipose depots of six men using the Illumina® HumanWG-6 v3.0 expression BeadChips. Twenty-three and 73 genes were differentially up-regulated in EAT compared to MAT and SAT, respectively. Ninety-four genes were down-regulated in EAT compared to SAT. However, none were significantly down-regulated in EAT compared to MAT. More specifically, the expression of the adenosine A1 receptor (ADORA1), involved in myocardial ischemia, was significantly up-regulated in EAT. Levels of the prostaglandin D2 synthase (PTGDS) gene, recently associated with the progression of atherosclerosis, were significantly different in the three pairwise comparisons (EAT>MAT>SAT). The results of ADORA1 and PTGDS were confirmed by quantitative real-time PCR in 25 independent subjects.Overall, the transcriptional profiles of EAT and MAT were similar compared to the SAT. Despite this similarity, two genes involved in cardiovascular diseases, ADORA1 and PTGDS, were differentially up-regulated in EAT. These results provide insights about the biology of EAT and its potential implication in CAD

Non-invasive cardiac imaging techniques and vascular tools for the assessment of cardiovascular disease in type 2 diabetes mellitus

Cardiovascular disease is the major cause of mortality in type 2 diabetes mellitus. The criteria for the selection of those asymptomatic patients with type 2 diabetes who should undergo cardiac screening and the therapeutic consequences of screening remain controversial. Non-invasive techniques as markers of atherosclerosis and myocardial ischaemia may aid risk stratification and the implementation of tailored therapy for the patient with type 2 diabetes. In the present article we review the literature on the implementation of non-invasive vascular tools and cardiac imaging techniques in this patient group. The value of these techniques as endpoints in clinical trials and as risk estimators in asymptomatic diabetic patients is discussed. Carotid intima–media thickness, arterial stiffness and flow-mediated dilation are abnormal long before the onset of type 2 diabetes. These vascular tools are therefore most likely to be useful for the identification of ‘at risk’ patients during the early stages of atherosclerotic disease. The additional value of these tools in risk stratification and tailored therapy in type 2 diabetes remains to be proven. Cardiac imaging techniques are more justified in individuals with a strong clinical suspicion of advanced coronary heart disease (CHD). Asymptomatic myocardial ischaemia can be detected by stress echocardiography and myocardial perfusion imaging. The more recently developed non-invasive multi-slice computed tomography angiography is recommended for exclusion of CHD, and can therefore be used to screen asymptomatic patients with type 2 diabetes, but has the associated disadvantages of high radiation exposure and costs. Therefore, we propose an algorithm for the screening of asymptomatic diabetic patients, the first step of which consists of coronary artery calcium score assessment and exercise ECG

NON-INVASIVE IMAGING Non-invasive assessment of coronary artery disease in diabetes

Vascular Biology and Interventio