Acute Coronary Syndromes and Diabetes Mellitus

Numerous trials have demonstrated a worse outcome for diabetic patients with acute coronary syndromes (ACS) compared with their nondiabetic counterparts.1 Because our knowledge of the influence of diabetes mellitus on ACS outcomes is based on subgroup analyses of randomized trials that are often post hoc and underpowered, most clinicians have not entertained the concept that we might consider approaching the diabetic patient differently. ACS trials, from the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial to the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial, have suggested that whereas diabetic patients may have a higher event rate, the relative risk with the use of the conventional antithrombotic therapies is comparable to that observed in the nondiabetic cohort.Article p 1626 Numerous mechanisms may explain this increased risk. Diabetic patients are more likely to have other comorbidities, such as renal insufficiency and hypertension, that lead to worse outcomes. Diabetic patients often have early signs of heart failure, particularly diastolic heart failure, which can lead to increasing morbidity and mortality.2 Perhaps the most important difference is that type 2 diabetes mellitus is associated with a proinflammatory and a prothrombotic state.3,4 Of interest, in the insulin-resistant state, perhaps through glycosylation, an upregulation of platelet membrane proteins such as the P2Y12 receptor/pathway takes place, which is the target of the active metabolite of clopidogrel.5 Thus, treatment with insulin may identify a group of subjects at particular risk for poor response to platelet inhibitors such as clopidogrel. Furthermore, glycosylation may increase oxidative stress and impair endothelial function, presumably resulting in more platelet reactivity as well as procoagulant activity.Within the context that diabetic patients may …