Marco Roffi and Michael Brandie


■ Diabetes-associated deaths, more that two thirds of them cardiovascular-related, are rising exponentially, following the diabetes "epidemics" observed in Western countries.

■ Diabetes confers a cardiovascular risk equivalent to aging 15 years.

■ Coronary artery disease is more prevalent, is more severe, and occurs at younger age in patients with diabetes. Chronic hyperglycemia, dyslipidemia, and insulin resistance have been associated with an accelerated form of atherogenesis, characterized by a pro-thrombotic state, enhanced inflammation, and endothelial dysfunction.

■ Diabetic patients undergoing coronary revascularization have worse outcomes compared with nondiabetic individuals, both in the setting of percutaneous coronary interventions (PCI) and in coronary artery bypass grafting (CABG). Subgroup analyses of randomized trials and registries have suggested that CABG is superior to PCI in diabetic patients with multivessel disease. Ongoing randomized trials that focus for the first time on diabetic patients may settle the controversy.

■ Diabetic patients with both non-ST-elevation acute coronary syndromes and ST-elevation myocardial infarction have higher short- and long-term morbidity and mortality rates than their nondiabetic counterparts. This finding is explained partly by a higher baseline risk profile and partly by a lesser degree of adherence to evidence-base therapies in this patient population. At the same time, however, diabetic patients derive a grater benefit than nondiabetic individuals from aggressive management, including early invasive strategy, glycoprotein IIb/IIIa inhibition, and possibly primary angioplasty.

■ The association between aggressive glucose-lowering strategies and reduction in diabetes-related adverse outcomes has been established in clinical trials for microvascular but not macrovascular complications. Nevertheless, optimization of the glucose level remains a main goal in diabetes treatment.

■ Aggressive modification of additional risk factors, including blood pressure and cholesterol level control, cigarette smoking cessation, weight loss, and exercise, is key cardiovascular prevention.

■ Metabolism modulation with thiazolidinediones has been associated in ex vivo studies with anti-inflammatory and thrombus-reducing properties. In addition, rosiglitazone has been shown to prevent diabetes in individuals with impaired glucose metabolism. However, a reduction in cardiovascular events associated with these agents has not yet been convincingly demonstrated.

■ The ultimate goal in diabetes care remains the cure of the disease by regeneration of beta-cell mass and/or beta-cell function. The role of pluripotent cells in this setting needs to be defined.

Diabetes mellitus defines a group of metabolic diseases that are characterized by dysfunction in insulin secretion, insulin action, or both. The resulting chronic hyperglycemia may cause failure of various organs, including eyes, kidneys, nerves, heart, and the arterial vasculature. In the last decades, an increase in the prevalence of diabetes of epidemic proportion has been observed in Western countries, and, with a delay, the developing world will follow a similar pattern. Diabetes-associated cardiovascular disease (CVD) involves both the macrovasculature and the microvasculature. The focus of this chapter is the macrovascular complications, specifically coronary artery disease (CAD); microvascular manifestations such as nephropathy, neuropathy, and retinopathy are only marginally addressed. The increased cardiovascular (CV) risk observed in individuals with diabetes is in part a consequence of the associated metabolic disturbances and in part is explained by the clustering of additional CV risk factors, such as hypertension, dyslipidemia, and central obesity. For the purpose of this chapter, "diabetes" refers to type 2 diabetes mellitus, which accounts for 90% to 95% of all diabetes cases in Western countries.

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