Improved Estimation of Human Lipoprotein Kinetics with Mixed Effects Models.

Context: Mathematical models may help the analysis of biological systems by providing estimates of otherwise un-measurable quantities such as concentrations and fluxes. The variability in such systems makes it difficult to translate individual characteristics to group behavior. Mixed effects models offer a tool to simultaneously assess individual and population behavior from experimental data.

Investigations of a compartmental model for leucine kinetics using non-linear mixed effects models with ordinary and stochastic differential equations.

Non-linear mixed effects (NLME) models represent a powerful tool to simultaneously analyse data from several individuals. In this study, a compartmental model of leucine kinetics is examined and extended with a stochastic differential equation to model non-steady-state concentrations of free leucine in the plasma. Data obtained from tracer/tracee experiments for a group of healthy control individuals and a group of individuals suffering from diabetes mellitus type 2 are analysed.

Modelling of peripheral fluid accumulation after a crystalloid bolus in female volunteers - a mathematical study.

Objective: To simultaneously model plasma dilution and urinary output in female volunteers.

Methods: Ten healthy female non-pregnant volunteers, aged 21-39 years (mean 29), with a bodyweight of 58-67 kg (mean 62.5 kg) participated.

Overproduction of VLDL1 driven by hyperglycemia is a dominant feature of diabetic dyslipidemia.

Objective: We sought to compare the synthesis and metabolism of VLDL1 and VLDL2 in patients with type 2 diabetes mellitus (DM2) and nondiabetic subjects.

Methods And Results: We used a novel multicompartmental model to simultaneously determine the kinetics of apolipoprotein (apo) B and triglyceride (TG) in VLDL1 and VLDL2 after a bolus injection of [2H3]leucine and [2H5]glycerol and to follow the catabolism and transfer of the lipoprotein particles. Our results show that the overproduction of VLDL particles in DM2 is explained by enhanced secretion of VLDL1 apoB and TG.

A new combined multicompartmental model for apolipoprotein B-100 and triglyceride metabolism in VLDL subfractions.

The use of stable isotopes in conjunction with compartmental modeling analysis has greatly facilitated studies of the metabolism of the apolipoprotein B (apoB)-containing lipoproteins in humans. The aim of this study was to develop a multicompartment model that allows us to simultaneously determine the kinetics of apoB and triglyceride (TG) in VLDL(1) and VLDL(2) after a bolus injection of [(2)H(3)]leucine and [(2)H(5)]glycerol and to follow the catabolism and transfer of the lipoprotein particles. Here, we describe the model and present the results of its application in a fasting steady-state situation in 17 subjects with lipid values representative of a Western population.