HDL subparticles and coronary artery disease in NIDDM

Decreased HDL cholesterol levels are associated with an increased risk of coronary artery disease (CAD) in non insulin dependent diabetes mellitus (NIDDM). The aim of this study was to compare HDL subparticles with apo A-I (LpAI) and those with apo A-I and apo A-II (LpAI/AII) in subjects with and without NIDDM and to study the relationship between HDL subparticles and CAD in NIDDM. Lipids, apo A-I and HDL subparticles were measured in 240 subjects with NIDDM and in 248 age and gender matched controls. Subjects with NIDDM had higher triglyceride levels (2.5 ± 1.8 vs. 1.4 ± 0.8 mmol/l, P < 0.001), lower HDL cholesterol (0.9 ± 0.3 vs. 1.2 ± 0.3 mmol/l, P < 0.001), apo A-I (124.7 ± 22.4 vs. 139.8 ± 24.1 mg/dl, P < 0.001) and LpAI/AII (82.4 ± 18.2 vs. 94.9 ± 16.7 mg/dl, P < 0.001) in comparison to controls. LpAI levels were similar in both groups. Diabetic subjects with CAD (n = 109) had higher triglycerides (2.7 ± 1.9 vs. 2.3 ± 1.8 mmol/l, P = 0.02) and lower HDL cholesterol (0.8 ± 0.2 vs. 1.0 ± 0.3 mmol/l, P < 0.001), apo A-I (115.5 ± 20.1 vs. 132.3 ± 21.4 mg/dl, P < 0.001), LpAI (40.2 ± 9.1 vs. 44.4 ± 12.4 mg/dl, P = 0.06), and LpAI/AII levels (75.4 ± 18.0 vs. 88.3 ± 16.2 mg/dl, P < 0.001) in comparison to diabetic subjects without CAD (n = 131). In a multivariate analysis, apo A-I was found to be the best predictor of CAD in subjects with NIDDM. In conclusion, reduced HDL cholesterol levels found in NIDDM are, principally, due to reduced concentrations of apo A-I and apo A-II-containing particles (LpAI/AII). While LpAI and LpAI/AII levels were lower in NIDDM subjects with CAD, plasma apo A-I is the best predictor of CAD in NIDDM.