In vivo evidence for the role of lipoprotein lipase activity in the regulation of apolipoprotein AI metabolism: A kinetic study in control subjects and patients with type II diabetes mellitus

The aim of this study was to delineate the role of lipoprotein lipase (LPL) activity in the kinetic alterations of high density lipoprotein (HDL) meta bolism in patients with type II diabetes mellitus compared with controls. T he kinetics of HDL were studied by endogenous labeling of HDL apolipoprotei n AI (HDL-apo AI) using a primed infusion of D-3-leucine. The HDL-apo AI fr actional catabolic rate (FCR) was significantly increased (0.32 +/- 0.07 vs . 0.23 +/- 0.05 pool/day; P < 0.01), and HDL composition was changed [HDL c holesterol, 0.77 +/- 0.16 vs. 1.19 +/- 0.37 mmol/L (P < 0.05); HDL triglyce rides, 0.19, 0.12 vs. 0.10 <plus/minus> 0.03 mmol/L (P < 0.05)] in diabetic patients compared with healthy subjects. HDL-apo AI FCR was correlated to plasma and HDL triglyceride concentrations (r = 0.82; P < 0.05 and r = 0.80 ; P < 0.05, respectively) and to homeostasis model assessment (r = 0.78; P < 0.05). Postheparin plasma LPL activity was decreased in type II diabetes (6.8 +/- 2.8 us. 18.1 +/- 5.2 mu mol/mL postheparin plasma h; P < 0.005) co mpared with that in healthy subjects and was correlated to the FCR of HDL-a po AI (r = -0.63; P < 0.05). LPL activity was also correlated with HDL chol esterol(r = 0.78; P < 0.05), plasma and HDL triglycerides (r = -0.87; P < 0 .005 and r = -0.83; P < 0.05, respectively), and homeostasis model assessme nt (r = -0.79; P < 0.05). In addition, the LPL to hepatic lipase ratio was correlated with the catabolic rate of HDL(r = -0.76; P <less than> 0.06). T hese results suggest that a decrease in the LPL to hepatic lipase ratio in type II diabetes mellitus, mainly related to lowered LPL activity, could in duce an increase in HDL catabolism. These alterations in HDL kinetics in ty pe II diabetes proceed to some extent from changes in their composition, pr obably linked to an increase in triglyceride transfer from very low density lipoprotein particles, in close relationship with LPL activity and resista nce to insulin.