Percutaneous Coronary Interventions in the Diabetic Patient

Clinical observations made during the past 20 years have suggested that patients with diabetes mellitus (DM) have suboptimal outcomes after percutaneous coronary interventions (PCIs).1–4 During the same time period, mechanistic studies have provided insights into the cardiovascular risk of DM. In this report, we attempt to synthesize observations made in the experimental laboratory with those made in the clinical setting to identify how diabetic traits may compromise the success of PCI (Figure 1).Figure 1. Diabetic traits potentially compromising the success of percutaneous coronary intervention.The hallmarks of DM are hyperglycemia, insulin resistance or an absolute lack of endogenous insulin, and hyperinsulinemia. These metabolic derangements may lead to premature atherosclerosis, cardiomyocyte dysfunction, and renal failure through several mechanisms. Diabetic ArteriopathyIn an early stage of atherogenesis, the presence of cholesterol crystals may induce the formation of small hydroxyapatite mineral clefts, which are also called microcalcifications, in the intima or media.5 In DM, medial calcification develops independently of hypercholesterolemia and may cause sheet-like calcific deposits that reduce vascular compliance.6 In the presence of hyperglycemia, medial calcification may be mediated by a glycosylation process, in which N-acetylglucosamine (O-GlcNAc) binds to serine and threonine residues of vascular proteins.7 In a drug-induced mouse model of type 1 DM, Heath et al6 found a strong increase in vascular O-GlcNAcylation after the onset of increased blood glucose levels, along with a significant increase in aortic calcium content and vascular stiffness. The connection between O-GlcNAcylation and the development of a mineralized matrix was confirmed in an experimental model of vascular smooth muscle cells cultured in osteogenic differentiation media along with an inhibitor of N-acetylglucosaminidase.6The formation of vulnerable atherosclerotic lesions may be related to hyperglycemia8 or insulin resistance.9 Kuroda et al8 observed that daily glucose fluctuations, measured as the …