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 lipo proteins in noninsulin-dependent diabetes mellitus (NIDDM) remain poorly un derstood. To get further insight into these abnormalities we performed a st able isotope kinetic experiment comparing the metabolism of apoB-containing lipoproteins in moderately severe NIDDM patients and healthy control subje cts. Methods The study was performed in the fed state. Subjects underwent a prim ed infusion of 0.7 mg kg(-1) of L-[1-C-13] leucine followed by a 16-h const ant infusion of 0.7 mg kg(-1) h(-1) [C-13]Leucine enrichment in apoB was me asured by gas chromatography/combustion/isotope ratio mass spectrometry. Results In NIDDM patients, we observed a 3.49- and 4.52-fold increase of ve ry-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 incr eased IDL apoB plasma concentration was also related to a major catabolic d efect (-78%; P < 0.01). For most patients, plasma LDL apoB concentration wa s comparable to that of controls. Nevertheless, LDL apoB metabolism was imp aired 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 ci rculating VLDL and IDL particles, the increased residence time observed on all apoB-containing lipoproteins may promote the development of atheroscler otic lesions, by potentiating their oxidizability.