D: Lipid management in the patient with diabetes Revascularization in patients with diabetes: The challenges Content points: National Heart, Lung, and Blood Institute (NHLBI) 1985–1986 PCTA Registry data on 281 patients with a history of diabetes and 1833 patients without diabetes reveal differences in clinical and angiographic characteristics that pose challenges to successful revascularization.1 Diabetic patients were older and had more concomitant disease, including CHF, hypertension, and hypercholesterolemia. Diabetics also suffered from more diffuse and more multivessel disease than nondiabetics. 1 Kip KE, Faxon DP, Detre KM, Yeh W, Kelsey SF, Currier JW, for the Investigators of the NHLBI PTCA Registry. Coronary angioplasty in diabetic patients: The National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry. Circulation. 1996;94:1818-1825.

Elevated CV risk in diabetes Content points: Diabetes is a risk factor for CV events and their underlying pathology. Atherosclerosis is accelerated in diabetics, who experience 2- to 4-fold greater rates of CV disease,1 2-fold greater incidence of post-MI mortality,2 and 3-fold greater rates for fatal stroke3 than nondiabetics. Hormonal abnormalities, including hyperinsulinemia and elevated levels of mitogens, such as insulin-like growth factor, may promote SMC proliferation.4 Consequently, diabetics may have a different arterial pathology and accelerated restenosis. 1 Sowers JR, Lester MA. Diabetes and cardiovascular disease. Diabetes Care. 1999;22(suppl 3):C14-C20. 2 Mukamal KJ, Maclure M, Nesto RW, Sherwood JB, Cohen MC, Mittleman MA, Muller JE. Impact of diabetes on long-term survival after acute myocardial infarction: Comparability of risk with prior myocardial infarction. Diabetes Care. 2001;24:1422-1427. 3 Grundy SM, Benjamin IJ, Burke GI, Chait A, Eckel RH, Howard BV, et al. Diabetes and heart disease: A statement for healthcare professionals from the American Heart Association. Circulation. 1999;100:1134-1146. 4 Kornowski R, Mintz GS, Kent KM, Pichard AD, Satler LF, Bucher TA, et al. Increased restenosis in diabetes mellitus after coronary interventions is due to exaggerated intimal hyperplasia: A serial intravascular ultrasound study. Circulation. 1997;95:1366-1369.

Potential mechanisms of elevated risk in diabetes Content points: Elevated risk for endothelial dysfunction in diabetics may result from effects of hyperglycemia that lead to depletion of NAD(P)H, which is essential for regeneration of antioxidant molecules and as a cofactor of eNOS.1 Ramifications of depleted NADPH include increases in the NADH/NAD+ ratio, protein kinase C, advanced glycation end products, and oxidative stress, as well as decreases in Na+K+ ATPase and antioxidant defenses. These changes affect the synthesis and degradation of, plus the responsiveness to, nitric oxide—a key factor for endothelial function. 1 Deedwania PC. Diabetes and vascular disease: Common links in the emerging epidemic of coronary artery disease. Am J Cardiol. 2003;91:68-71.

Exaggerated intimal hyperplasia in diabetics following stenting Content points: VUS follow-up of 241 patients with and without diabetes was used to measure changes in tissue growth (intimal hyperplasia cross-sectional area [CSA] and lumen CSA).1 5.6 months after stenting, diabetics showed greater decreases in lumen CSA as well as greater increases in tissue growth than nondiabetics. This result may explain the increased rate of restenosis seen in patients with diabetes. 1 Kornowski R, Mintz GS, Kent KM, Pichard AD, Satler LF, Bucher TA, et al. Increased restenosis in diabetes mellitus after coronary interventions is due to exaggerated intimal hyperplasia: A serial intravascular ultrasound study. Circulation. 1997;95:1366-1369.

Event rates (statin vs placebo) in diabetic cohorts of randomized trials Content points: Statins show substantial benefits for treatment of diabetic patients, as demonstrated in several primary- and secondary-prevention studies.1 Statin therapy of diabetic cohorts in five separate randomized trials caused relative reduction in rates of fatal and nonfatal MI, fatal CHD, stroke, and revascularization of 17% to over 50%. 1 Kornowski R, Mintz GS, Kent KM, Pichard AD, Satler LF, Bucher TA, et al. Increased restenosis in diabetes mellitus after coronary interventions is due to exaggerated intimal hyperplasia: A serial intravascular ultrasound study. Circulation. 1997;95:1366-1369.

Proposed lipid-lowering algorithm in hypertensive diabetic patients Content points: The first priority for lipid reduction in diabetics with hypertension is achieving LDL-C <100 mg/dL via statin therapy.1 ADA (American Diabetes Association) and NCEP (National Cholesterol Education Program) differ slightly on their second goal: ADA targets HDL-C to >45 mg/dL and triglycerides to <200 mg/dL NCEP recommends that after the LDL-C goal is met, non–HDL-C be determined and reduced to <200 mg/dL if triglycerides are >200 mg/dL Therapy should be increased as needed to achieve goals, starting with upward titration of statins, followed by fibric acid at low doses in patients without renal compromise. Nicotinic acid may worsen glycemic control and insulin resistance, although data suggest the effect may be modest at low dose.1 1 Sowers JR, Haffner S. Treatment of cardiovascular and renal risk factors in the diabetic hypertensive. Hypertension. 2002;40:781-788.