IN-VIVO EVIDENCE FOR INCREASED APOLIPOPROTEIN-A-I CATABOLISM IN SUBJECTS WITH IMPAIRED GLUCOSE-TOLERANCE

The in vivo kinetics of the HDL apolipoproteins (apo) A-I and A-II wer e studied in six subjects with impaired glucose tolerance (IGT) and si x control subjects with normal glucose tolerance (NGT), using a stable isotope approach. During a 12-h primed constant infusion of L-[ring-C -13(6)] -phenylalanine, tracer enrichment was determined in apoA-I and apoA-II from ultracentrifugally isolated HDL. The rates of HDL apoA-I and apoA-II production and catabolism were estimated using a one-comp artment model-based analysis. Triglycerides were higher in IGT subject s (1.33 +/- 0.21 vs. 0.84 +/- 0.27 mmol/l, P < 0.05), but were within the normal range. HDL cholesterol and apoA-I levels were significantly lower in subjects with IGT (1.07 +/- 0.15 vs. 1.36 +/- 0.14 mmol/l, P < 0.05; 0.94 +/- 0.10 vs. 1.34 +/- 0.07 g/l, P < 0.01). In IGT subjec ts, HDL composition was significantly altered, characterized by an inc rease in HDL triglycerides (4.9 +/- 1.9 vs. 3.2 +/- 1.0%, P < 0.05) an d HDL phospholipids (34.7 +/- 2.6 vs. 27.5 +/- 5.8%, P < 0.05) and a d ecrease in HDL cholesteryl eaters (10.1 +/- 2.0 vs. 12.7 +/- 2.9%, P < 0.05) and HDL apoA-I (31.5 +/- 4.4 vs. 43.2 +/- 2.4%, P < 0.05). The mean fractional catabolic rate (FCR) of HDL apoA-I was significantly h igher in IGT subjects (0.34 +/- 0.05 vs. 0.26 +/- 0.03 day(-1), P < 0. 01), while the HDL apoA-I production rate (PR), as well as the PR and FCR of HDL apoA-II, showed no differences between the two groups. Ther e were significant correlations between HDL apoA-I FCR and the followi ng parameters: HDL apoA-I (r = -0.902, P < 0.001), HDL cholesterol (r = -0.797, P = 0.001), plasma triglycerides (r = 0.743, P < 0.01), HDL triglycerides (r = 0.696, P < 0.01), and cholesterol ester transfer pr otein activity (r = 0.646, P < 0.01). We observed a strong positive as sociation between increased apoA-I catabolism and insulin (r = 0.765, P < 0.01) and proinsulin (r = 0.797, P < 0.01) concentrations. These d ata support the hypothesis that the decrease in HDL cholesterol and ap oA-I levels in IGT is principally the result of an enhanced apoA-I cat abolism. The latter seems to be an early metabolic finding in IGT even when other lipid parameters, especially plasma triglycerides, still a ppear to be not or only weakly affected.