Long-term effects of fenofibrate on lipoproteins and surrogate markers of macrovascular and microvascular disease in people with type 2 diabetes

Background and aims. Diabetic dyslipidemia is a highly atherogenic triad of increased triglycerides, decreased HDL cholesterol, and small dense LDL. Fibrates have a beneficial effect on diabetic dyslipidemia, and they have reduced cardiovascular events in randomized trials. Fenofibrate has reduced albuminuria and markers of low-grade inflammation and endothelial dysfunction. The present studies were undertaken to characterize the alterations of VLDL and LDL subclasses and to investigate the binding of LDL to arterial wall in type 2 diabetes. Further purpose was to elucidate the effects of fenofibrate on several lipoprotein subclasses, augmentation index (AIx), carotid intima-media thickness (IMT), and renal function. Subjects. 239 type 2 diabetic subjects were recruited among participants of the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study at the Helsinki centre. The patients were randomized to fenofibrate (200mg/d) or placebo for 5 years. Additionally, a healthy control group (N = 93) was recruited. Results. VLDL1 triglycerides increased in similar proportion to total triglycerides in type 2 diabetic patients and control subjects. Despite the increase in total apoCIII levels, VLDL apoCIII was decreased in diabetic patients. Enrichment of LDL with apoCIII induced a small increase in binding of LDL to arterial wall proteoglycan. Intrinsic characteristics of diabetic LDL, rather than levels of apoCIII, were responsible for increased proteoglycan binding of diabetic LDL with high apoCIII. Fenofibrate reduced triglycerides, increased LDL size, and shifted HDL subclasses towards smaller particles with no change in levels of HDL cholesterol. High levels of homocysteine were associated with lower increase of HDL cholesterol and apoA-I during fenofibrate treatment. Long-term fenofibrate treatment did not improve IMT, AIx, inflammation, or endothelial function. Fenofibrate decreased creatinine clearance and estimated glomerular filtration rate. No effect on albuminuria was seen with fenofibrate. Instead, Cystatin C was increased during fenofibrate treatment. Conclusions. 1) Elevation of VLDL 1 triglycerides was the major determinant of plasma triglyceride concentration in control subjects and type 2 diabetic patients. 2) LDL with high apoCIII showed multiple atherogenic properties, that were only partially mediated by apoCIII per se in type 2 diabetes 3) Fenofibrate demonstrated no effect on surrogate markers of atherosclerosis. 4) Fenofibrate had no effect on albuminuria and the observed decrease in markers of renal function could complicate the clinical surveillance of the patients. 5) Fenofibrate can be used to treat severe hypertriglyceridemia or in combination therapy with statins, but not to increase HDL levels.

Conditionally One of 'Us' : A Study of Print Media, Minorities and Positioning Practices

This study deals with how ethnic minorities and immigrants are portrayed in the Finnish print media. The study also asks how media users of various ethnocultural backgrounds make sense of these mediated stories. A more general objective is to elucidate negotiations of belonging and positioning practices in an increasingly complex society. The empirical part of the study is based on content analysis and qualitative close reading of 1,782 articles in five newspapers (Hufvudstadsbladet, Vasabladet, Helsingin Sanomat, Iltalehti and Ilta-Sanomat) during various research periods between 1999 and 2007. Four case studies on print media content are followed up by a focus group study involving 33 newspaper readers of Bosnian, Somalian, Russian, and 'native' Finnish backgrounds. The study draws from different academic and intellectual traditions; mainly media and communication studies, sociology and social psychology. The main theoretical framework employed is positioning theory, as developed by Rom Harré and others. Building on this perspective, situational self-positioning, positioning by others, and media positioning are seen as central practices in the negotiation of belonging. In support of contemporary developments in social sciences, some of these negotiations are seen as occurring in a network type of communicative space. In this space, the media form one of the most powerful institutions in constructing, distributing and legitimising values and ideas of who belongs to 'us', and who does not. The notion of positioning always involves an exclusionary potential. This thesis joins scholars who assert that in order to understand inclusionary and exclusionary mechanisms, the theoretical starting point must be a recognition of a decent and non-humiliating society. When key insights are distilled from the five empirical cases and related to the main theories, one of the major arguments put forward is that the media were first and foremost concerned with a minority actor's rightful or unlawful belonging to the Finnish welfare system. However, in some cases persistent stereotypes concerning some immigrant groups' motivation to work, pay taxes and therefore contribute are so strong that a general idea of individualism is forgotten in favour of racialised and stagnated views. Discussants of immigrant background also claim that the positions provided for minority actors in the media are not easy to identify with; categories are too narrow, journalists are biased, the reporting is simplifying and carries labelling potential. Hence, although the will for the communicative space to be more diverse and inclusive exists — and has also in many cases been articulated in charters, acts and codes — the positioning of ethnic minorities and immigrants differs significantly from the ideal.