Metabolic abnormalities of apolipoprotein B-containing lipoproteins in non-insulin-dependent diabetes: a stable isotope kinetic study.

BACKGROUND: Kinetic abnormalities of apolipoprotein B (apoB)-containing lipoproteins in noninsulin-dependent diabetes mellitus (NIDDM) remain poorly understood. To get further insight into these abnormalities we performed a stable isotope kinetic experiment comparing the metabolism of apoB-containing lipoproteins in moderately severe NIDDM patients and healthy control subjects.

METHODS: The study was performed in the fed state. Subjects underwent a primed infusion of 0.7 mg kg(-1) of L-[1-(13)C]leucine followed by a 16-h constant infusion of 0.7 mg kg(-1) h(-1). [13C]Leucine enrichment in apoB was measured by gas chromatography/combustion/isotope ratio mass spectrometry.

RESULTS: In NIDDM patients, we observed a 3.49- and 4.52-fold increase of very-low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) apoB plasma concentrations, respectively (P<0.01). VLDL apoB production was increased by 41% (P<0.05) and fractional catabolic rate towards IDL and low-density lipoprotein (LDL) was decreased by 61% (P<0.05). The increased IDL apoB plasma concentration was also related to a major catabolic defect (-78%; P<0.01). For most patients, plasma LDL apoB concentration was comparable to that of controls. Nevertheless, LDL apoB metabolism was impaired in NIDDM subjects, with both a decreased LDL catabolic rate (-28%; P<0.05) and a trend towards a diminished synthesis.

CONCLUSION: NIDDM is associated with multiple apoB metabolism abnormalities that are potentially atherogenic. In addition to the increased number of circulating VLDL and IDL particles, the increased residence time observed on all apoB-containing lipoproteins may promote the development of atherosclerotic lesions, by potentiating their oxidizability.