REGULATION OF APOLIPOPROTEIN A-I-CONTAINING LIPOPROTEINS IN IDDM

In IDDM patients, serum high-density lipoprotein cholesterol concentra tions have been reported to be normal or elevated. The spectrum of hig h-density lipoprotein particles is highly heterogeneous, but no data a re available on the subpopulations of high-density lipoprotein in IDDM . We, therefore, studied the spectrum of high-density lipoprotein part icles in 86 IDDM patients (51 men and 35 women) 37 +/- 10 yr of age an d in 74 sex-, age-, and body mass index-matched healthy nondiabetic su bjects. The concentrations of high-density lipoprotein and HDL2 choles terol 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 tha n in the nondiabetic subjects (P < 0.001) because of an increased conc entration of LpA-I particles (61 +/- 17 vs. 53 +/- 15, P < 0.01). LpA- 1 particles correlated positively with high-density lipoprotein and HD L2 cholesterol in the two groups. Postheparin plasma lipoprotein lipas e activity was significantly higher in the IDDM group than in the cont rol group (P < 0.001), whereas postheparin plasma hepatic lipase activ ities were similar in both groups. Plasma cholesteryl ester transfer p rotein activity was estimated in an in vitro isotopic assay using exog enous labeled donor (low-density) and acceptor (high-density) lipoprot eins 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 transfe r protein activity and high-density lipoprotein subpopulations. A posi tive correlation existed between HDL2 cholesterol and lipoprotein lipa se-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-1 particles and lipoprotein lipase-to- hepatic lip ase ratio in both groups (r = 0.34, P < 0.01; r = 0.38, P < 0.01, resp ectively) suggesting that lipolytic enzymes participate in the regulat ion of the metabolism of LpA-I particles. In conclusion, the elevation of high-density lipoprotein cholesterol in IDDM patients is mainly ca used by a rise of LpA-I particles, which are suggested to have a key r ole in reverse cholesterol transport.