End organ damage in the metabolic syndrome and diabetes mellitus : biochemical and magnetic resonance imaging studies

Abstract

The focus of this thesis was to evaluate biomarkers of cardiovascular end organ damage in the metabolic syndrome and diabetes mellitus. We performed cross-sectional studies with biochemical and magnetic resonance imaging (MRI) techniques. We have demonstrated that insulin resistance is a strong risk predictor for CVD and we provided a novel link between inflammation and angiopoietin-like protein 4 (ANGPTL4) expression by showing that ANGPTL4 levels in humans are related to systemic inflammation and inflammatory stimuli increased ANGPTL4 expression using human macrophages in vitro. The imaging studies described in this thesis extend the knowledge of end organ damage and explored the relation with aortic stiffness. The impact of type 1 diabetes mellitus (T1DM) on regional grey matter was investigated and showed atrophy of all subcortical grey matter structures but the amygdala. By showing an association of aortic stiffness with subtle microstructural deficits in T1DM and kidney function in patients with hypertension the close link between aortic stiffness and the microcirculation is demonstrated. Furthermore regional and individual differences in response to an oral glucose load in MR assessed aortic stiffness were observed, which may open new future research paths possibly linking inter-individual variation in regional vascular response and CVD.