Additional file 2: Table S2. of The impact of micronutrient status on health: correlation network analysis to understand the role of micronutrients in metabolic-inflammatory processes regulating homeostasis and phenotypic flexibility

Plasma vitamin and carotenoid levels coherence. (DOC 18 kb

Additional file 1: Table S1. of The impact of micronutrient status on health: correlation network analysis to understand the role of micronutrients in metabolic-inflammatory processes regulating homeostasis and phenotypic flexibility

Nutritional composition of nutritional challenge test (NCT). (DOC 18 kb

Clustering by Plasma Lipoprotein Profile Reveals Two Distinct Subgroups with Positive Lipid Response to Fenofibrate Therapy

<div><p>Fibrates lower triglycerides and raise HDL cholesterol in dyslipidemic patients, but show heterogeneous treatment response. We used k-means clustering to identify three representative NMR lipoprotein profiles for 775 subjects from the GOLDN population, and study the response to fenofibrate in corresponding subgroups. The subjects in each subgroup showed differences in conventional lipid characteristics and in presence/absence of cardiovascular risk factors at baseline; there were subgroups with a low, medium and high degree of dyslipidemia. Modeling analysis suggests that the difference between the subgroups with low and medium dyslipidemia is influenced mainly by hepatic uptake dysfunction, while the difference between subgroups with medium and high dyslipidemia is influenced mainly by extrahepatic lipolysis disfunction. The medium and high dyslipidemia subgroups showed a positive, yet distinct lipid response to fenofibrate treatment. When comparing our subgroups to known subgrouping methods, we identified an additional 33% of the population with favorable lipid response to fenofibrate compared to a standard baseline triglyceride cutoff method. Compared to a standard HDL cholesterol cutoff method, the addition was 18%. In conclusion, by using constructing subgroups based on representative lipoprotein profiles, we have identified two subgroups of subjects with positive lipid response to fenofibrate therapy and with different underlying disturbances in lipoprotein metabolism. The total subgroup with positive lipid response to fenofibrate is larger than subgroups identified with baseline triglyceride and HDL cholesterol cutoffs.</p> </div

Mean standardized particle concentrations (unitless) of NMR lipoprotein subclasses in three subgroups based on K-means clustering.

<p>Particle sizes of the various subclasses were the same as described in Freedman, <i>et al. </i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038072#pone.0038072-Freedman1" target="_blank">[38]</a>.</p

Percent changes after fenofibrate intervention, grouped by NMR clustering.

†<p>indicates significantly different with respect to cluster 1, p<0.01.</p>‡<p>indicates significantly different with respect to cluster 2, p<0.01.</p>*<p>LDL/HDL particle number (measured by NMR).</p

Overview of the data analysis approach presented in this paper.

<p>Clustering was carried out to identify representative lipoprotein profiles. The computational model analyzed those representative lipoprotein profiles. In the corresponding subgroups baseline characteristics and the lipid response to fenofibrate intervention was studied. The results of the subgroup studies were compared to the baseline characteristics and lipid response to fenofibrate in subgroups identified using triglyceride or HDL cholesterol cut-off methods.</p

Additional file 1: Table S1. of Multi-parameter comparison of a standardized mixed meal tolerance test in healthy and type 2 diabetic subjects: the PhenFlex challenge

Health biomarkers related to phenotypic flexibility. (DOCX 42 kb

Percent changes after fenofibrate intervention in medium TG subgroup versus lipoprotein cluster 2.

†<p>indicates significantly different with respect to cluster 2 and medium TG subgroup, p<0.01.</p>‡<p>indicates significantly different with respect to cluster 2 and not medium TG subgroup, p<0.01.</p>*<p>LDL/HDL particle number (measured by NMR).</p

Percent changes after fenofibrate intervention in high TG subgroup versus lipoprotein cluster 3.

†<p>indicates significantly different with respect to cluster 3 and high TG subgroup, p<0.01.</p>‡<p>indicates significantly different with respect to cluster 3 and not high TG subgroup, p<0.01.</p>*<p>LDL/HDL particle number (measured by NMR).</p

Subject overlaps between different subgroup identification methods. A:

<p>Subject overlap between the low HDLc subgroup (dark circle) and the sum of lipoprotein profile-based cluster 2 and 3 (light circle). Figures indicate the number of subjects in each group, in absolute numbers and as percentage of the total study population. <b>B:</b> Subject overlap between the high baseline-triglyceride subgroup (dark circle) and lipoprotein profile-based cluster 3 (light circle). Figures indicate the number of subjects in each group, in absolute numbers and as percentage of the total study population. <b>C:</b> Subject overlap between the medium baseline-triglyceride subgroup (dark circle) and lipoprotein profile-based cluster 2 (light circle). Figures indicate the number of subjects in each group, in absolute numbers and as percentage of the total study population. Lipoprotein cluster 2 clearly identifies a larger group of fibrate responders than the medium baseline-TG group.</p