Is atherosclerosis in diabetes and impaired fasting glucose driven by elevated LDL cholesterol or by decreased HDL cholesterol?

OBJECTIVE To evaluate the atherogenicity of lipids in coronary patients with normal fasting glucose (NFG), impaired fasting glucose (IFG), and type 2 diabetes. RESEARCH DESIGN AND METHODS Serum lipid values, the presence of angiographic coronary artery disease (CAD) at baseline, and the incidence of vascular events over 2.3 years were recorded in 750 consecutive patients undergoing coronary angiography. RESULTS Triglycerides significantly (P < 0.001) increased and HDL cholesterol (P < 0.001) as well as LDL particle diameter (P < 0.001) significantly decreased from subjects with NFG <5.6 mmol/l (n = 272) over patients with IFG > or =5.6 mmol/l (n = 314) to patients with type 2 diabetes (n = 164). Factor analysis revealed two factors in the lipid profiles of our patients: triglycerides, HDL cholesterol, apolipoprotein A1, and LDL particle diameter loaded high on an HDL-related factor, and total cholesterol, LDL cholesterol, and apolipoprotein B loaded high on an LDL-related factor. In patients with type 2 diabetes, the HDL-related factor (odds ratio 0.648 [95% CI 0.464-0.904]; P = 0.011), but not the LDL-related factor (0.921 [0.677-1.251]; P = 0.597), was associated with significant coronary stenoses > or =50%. Consistently, in the prospective study, the HDL-related factor (0.708 [0.506-0.990]; P = 0.044), but not the LDL-related factor (1.362 [0.985-1.883]; P = 0.061), proved significantly predictive for vascular events in patients with type 2 diabetes. CONCLUSIONS The low HDL cholesterol/high triglyceride pattern is associated with the degree of hyperglycemia. In coronary patients with type 2 diabetes, this pattern correlates with the prevalence of CAD and significantly predicts the incidence of vascular events.