Regulation of Apolipoprotein A-I–Containing Lipoproteins in IDDM

Abstract

In IDDM patients, serum high-density lipoprotein cholesterol concentrations have been reported to be normal or elevated. The spectrum of high-density lipoprotein particles is highly heterogeneous, but no data are available on the subpopulations of high-density lipoprotein in IDDM. We, therefore, studied the spectrum of high-density lipoprotein particles in 86 IDDM patients (51 men and 35 women) 37 ± 10 yr of age and in 74 sex-, age-, and body mass index-matched healthy nondiabetic subjects. The concentrations of high-density lipoprotein and HDL2 cholesterol were higher in the IDDM group than in the control subjects (P < 0.01). The apoA-I-to-apoA-II ratio was higher in the IDDM patients than in the nondiabetic subjects (P < 0.001) because of an increased concentration of LpA-I particles (61 ± 17 vs. 53 ± 15, P < 0.01). LpA-I particles correlated positively with high-density lipoprotein and HDL2 cholesterol in the two groups. Postheparin plasma lipoprotein lipase activity was significantly higher in the IDDM group than in the control group (P < 0.001), whereas postheparin plasma hepatic lipase activities were similar in both groups. Plasma cholesteryl ester transfer protein activity was estimated in an in vitro isotopic assay using exogenous labeled donor (low-density) and acceptor (high-density) lipoproteins in the absence of native lipoproteins. We observed no difference in cholesteryl ester transfer protein activity between the groups, and no significant correlations existed between cholesteryl ester transfer protein activity and high-density lipoprotein subpopulations. A positive correlation existed between HDL2 cholesterol and lipoprotein lipase-to-hepatic lipase ratio in IDDM patients (r = 0.35, P = 0.001) and in nondiabetic subjects (r = 0.55, P < 0.001). A positive correlation existed between LpA-I particles and lipoprotein lipase-to-hepatic lipase ratio in both groups (r = 0.34, P < 0.01; r = 0.38, P < 0.01, respectively) suggesting that lipolytic enzymes participate in the regulation of the metabolism of LpA-I particles. In conclusion, the elevation of high-density lipoprotein cholesterol in IDDM patients is mainly caused by a rise of LpA-I particles, which are suggested to have a key role in reverse cholesterol transport.