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Diagnostic markers based on a computational model of lipoprotein metabolismAbstract: We found that the model could fit a range of normolipidemic and dyslipidemic subjects from fifteen out of sixteen studies equally well, with an average 8.8% ± 5.0% fit error; only one study showed a larger fit error. As initial indication of clinical usefulness, we showed that one diagnostic marker based on VLDL metabolic ratios better distinguished dyslipidemic from normolipidemic subjects than triglycerides, HDL cholesterol, or LDL cholesterol. The VLDL metabolic ratios outperformed each of the classical diagnostics separately; they also added power of distinction when included in a multivariate logistic regression model on top of the classical diagnostics.In this study we further developed, calibrated, and corroborated the Particle Profiler computational model using pooled lipoprotein metabolic flux data. From pooled lipoprotein metabolic flux data on dyslipidemic patients, we derived VLDL metabolic ratios that better distinguished normolipidemic from dyslipidemic subjects than standard diagnostics, including HDL cholesterol, triglycerides and LDL cholesterol. Since dyslipidemias are closely linked to cardiovascular disease and diabetes type II development, lipoprotein metabolic ratios are candidate risk markers for these diseases. These ratios can in principle be obtained by applying Particle Profiler to a single lipoprotein profile measurement, which makes clinical application feasible.Dyslipidemia is an important risk factor for cardiovascular disease and type II diabetes. Especially low-density lipoprotein (LDL) cholesterol and LDL particle concentrations are known to be positively associated with cardiovascular disease risk [1], and reaching low LDL cholesterol concentrations is a primary goal for therapy [2]. Other recognized markers for metabolic syndrome include triglycerides and HDL cholesterol [2]. LDL particles contain the protein apoB, and are to a large extent a metabolic product of the larger apoB-containing lipoproteins, very low density lipoprotei
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