Insulin resistance and adipose tissue in the development of vascular diseases in high-risk patients

The work in this thesis focused on the relationship between presence of insulin resistance and advanced vascular damage in patients with manifest atherosclerotic vascular disease, and on the occurrence of (new) vascular events in insulin resistant patients with and without evident vascular disease. Also, the relationship between adipose tissue (abdominal fat and fat surrounding coronary arteries) and atherosclerotic vascular damage was examined. Patients with evident vascular disease or high insulin resistance (e.g. patients with metabolic syndrome or type 2 diabetes) are particularly prone to develop (new) vascular diseases. We demonstrated that metabolic syndrome, the clustering of vascular risk factors associated with insulin resistance, was highly prevalent (46%) in patients with manifest arterial disease. Also, an elevated level of insulin resistance was associated with an increased prevalence of albuminuria in patients with arterial disease. This association was only partly mediated by components of metabolic syndrome. High insulin resistance was not associated with an increased carotid intima-media thickness. Thus, insulin resistance may play a role in different stages of the atherosclerotic process. Another study showed that diabetic patients with cerebrovascular disease, coronary heart disease or peripheral arterial disease had a similar three- to fourfold higher risk of new vascular events, compared with diabetic patients without vascular disease. Diabetic patients with two or more clinical manifestations of atherosclerosis at different vascular sites had an even higher cardiovascular risk. Counting the number of sites of evident vascular disease, irrespective of the type of vascular disease, may help to simply identify those patients with diabetes type 2 particularly at very high risk for new macrovascular complications from a generally high-risk diabetic population. In case of obesity, an imbalanced production of pro- and anti-inflammatory cytokines by abdominal fat not only induces insulin resistance and consequently metabolic syndrome, but also leads directly to the development of endothelial dysfunction and progression of atherosclerosis. We found that infrarenal aortic diameter was larger in patients with more intra-abdominal fat compared to those with less intra-abdominal fat, suggesting that intra-abdominal fat may play a role in the process of aortic dilatation. Also, there is growing evidence that the adipose tissue directly surrounding the coronary arteries may affect atherogenesis from ‘outside to inside’ by the local release of a large number of pro-inflammatory factors. We determined the reproducibility of various measurements (thickness, area, volume) for quantifying epicardial adipose tissue (EAT) and peri-coronary fat using cardiac CT scans of patients undergoing coronary angiography (CAG). Volumetric quantifications of EAT were highly reproducible (coefficient of variations (CVs) 3%-5%) compared to thickness and area measurements of EAT and peri-coronary fat (CVs 11%-23%). EAT and peri-coronary fat accumulations were both associated with obesity and presence of metabolic syndrome in these patients. EAT volume and peri-coronary fat thickness were not associated with the severity of coronary atherosclerosis and extent of CAC in the whole study population. Nonetheless, in patients with a BM