Diabetes mellitus, inflammation and coronary atherosclerosis: Current and future perspectives

Type 2 diabetes mellitus is a condition associated with an increased risk o f coronary artery disease. This condition is currently reaching epidemic pr oportions in the Western world. Epidemiological studies have shown that ins ulin resistance and the constellation of metabolic alterations associated w ith type 2 diabetes mellitus such as dyslipidaemia, systemic hypertension, obesity and hypercoagulability, have an effect on the premature onset and s everity of atherosclerosis. Albeit direct, the link between insulin resista nce and atherogenesis is rather complex. It is likely that its complexity r elates to the interaction between genes that predispose to insulin resistan ce and genes that independently regulate lipid metabolism, coagulation proc esses and biological responses of the arterial wall. The rapid development of molecular biology in recent years has resulted in a better understanding of the immune and inflammatory mechanisms that underlie insulin resistance and atherosclerosis. For example, it is known that nuclear transcription f actors such as nuclear factor kappa beta and peroxisome proliferator-activa ted receptor gamma are involved in atherosclerosis. The former modulates ge ne expression which encodes pro-inflammatory proteins vital for the develop ment of the atheromatous plaque. In the presence of insulin resistance ther e are multiple activating factors that could explain the early onset and se verity of atherosclerosis. Glitazones, the new oral antidiabetic drugs and agonists of peroxisome proliferator-activated receptor gamma, have been sho wn to improve peripheral insulin sensitivity and to also delay atherosclero sis progression in experimental models. Their beneficial effects have been linked to their anti-inflammatory effect.