High density lipoprotein apolipoprotein Al kinetics in NIDDM: A stable isotope study

High density lipoprotein (HDL) kinetics were studied by infusing [5,5,5-H-2(3)]-leucine in five subjects with normal glucose tolerance and eight patients with non-insulin-dependent diabetes mellitus (NIDDM) with poor metabolic control (HbA(1c) = 8.16 +/- 1.93%) (mean +/- SD). HDL were modelled as a single compartment since no kinetic differences were observed between HDL2 and HDL3 subclasses. Plasma apolipoprotein AI (ape Al) concentration was significantly lower in NIDDM patients (96.1 +/- 12.1 vs 124.4 +/- 13.1 mg.dl(-1), p < 0.01). HDL composition was altered in NIDDM, as an increase in HDL-triglyceride and a decrease in HDL-cholesterol, negatively correlated (r = -0.780, p < 0.01). The mean fractional catabolic rate (FCR) of apo AI-HDL was significantly higher (0.39 +/- 0.16 vs 0.21 +/- 0.06 d(-1), p < 0.05) while the apo AI-HDL absolute production rate was not significantly greater (13.6 +/- 5.1 vs 12.0 +/- 4.2 mg.kg(-1).d(-1)) in diabetic patients compared to normal subjects. There were significant correlations between apo AI-HDL FCR and plasma apo AI concentration (r = -0.580, p < 0.05), plasma triglycerides (r = 0.839, p < 0.001) or HDL-triglyceride levels (r = 0.597, p < 0.05), No correlation was observed between apo AI-HDL FCR and HbA(1c) or HDL-cholesterol level. These data support the view that the decrease in plasma apo AI level in patients with NIDDM is due to an increase of apo AI-HDL FCR, which may itself be related to changes in HDL composition.