Abstract: Atherosclerosis is a major vascular complication of diabetes and the primary cause of mortality in patients with this disease. Inflammation has been implicated in the pathogenesis, progression and complications of both atherosclerosis and diabetes type 2, and these two complex disorders are often found intertwined in the patients. Peroxisome proliferatoractivated receptors-γ (PPARs-γ) are nuclear receptors that have been involved as transcriptional mediators in glucose homeostasis, lipid metabolism, and adipogenesis. PPAR-γ agonists, the thiazolidinediones (TZDs) are antidiabetic drugs that increase insulin sensitivity, lower blood glucose, decrease triglycerides and free fat acids and seem to have antiinflammatory effects as they reduce inflammatory markers and improve cardiovascular risk factors. All the major cell types in the vasculature express PPAR-γ including macrophages and vascular smooth muscle found cells in human atheroma. Activation of PPAR-γ by thiazolidinediones blocks vascular smooth muscle cells growth and migration thus reducing atherosclerosis. Several clinical studies have illustrated the beneficial role of thiazolidinediones in the atherosclerosis process, as they ameliorate endothelial dysfunction, reduce intima media thickness (IMT) in the carotid arteries and the restenosis rate after coronary stent implantation. However, recent trials have raised significant concerns about the deleterious action of thiazolidinediones, particularly rosiglitazone, on the cardiovascular system. Weighing the potential beneficial and harmful role of thiazolidinediones and exploring the possible mechanisms may provide a thorough view about the optimum clinical use of these compounds.
Abstract: Atherosclerotic disease is the leading cause of both morbidity and mortality in patients with type 2 diabetes. In these patients, postprandial dyslipidemia include not only quantitative but also qualitative abnormalities of lipoproteins which are potentially atherogenic and seems to be a significant risk factor for cardiovascular disease since there is evidence that it results in endothelial dysfunction and enhanced oxidative stress. The most common pattern of postprandial dyslipidemia in diabetes consists of high concentrations of triglycerides, higher VLDLs production by the liver and a decrease in their clearance, a predominance of small dense LDL particles, and reduced levels of HDL. The cause of this postprandial dyslipidemia in diabetes is complex and involves a variety of factors including hyperinsulinemia, insulin resistance, hyperglycemia and disturbed fatty acid metabolism. Numerous clinical studies have shown that postprandial dyslipidemia is associated with endothelial dysfunction in type 2 diabetes and with alterations in other surrogate markers in the cascade of atherosclerosis. Current published guidelines indicate that in diabetics the primary lipid target is LDL<100 mg/dL (70 mg/dL in very high-risk patients) and the most appropriate class of drugs are statins although the issue of postprandial dyslipidemia has not been specifically addressed so far. Moreover, several other classes of medications (fibrates, niacin and antidiabetic drugs) as well as non-pharmacological interventions (i.e. diet, smoking cessation and exercise) can be used to treat lipid and lipoprotein abnormalities associated with insulin resistance and type 2 diabetes. These type of interventions may be more appropriate to ameliorate postprandial dyslipidemia. However, this remains to be confirmed on clinical grounds.
