Metabolic Profiling of the Response to an Oral Glucose Tolerance Test Detects Subtle Metabolic Changes
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{"title"=>"Metabolic profiling of the response to an oral glucose tolerance test detects subtle metabolic changes", "type"=>"journal", "authors"=>[{"first_name"=>"Suzan", "last_name"=>"Wopereis", "scopus_author_id"=>"35235622400"}, {"first_name"=>"Carina M.", "last_name"=>"Rubingh", "scopus_author_id"=>"14061177000"}, {"first_name"=>"Marjan J.", "last_name"=>"Van Erk", "scopus_author_id"=>"8786490800"}, {"first_name"=>"Elwin R.", "last_name"=>"Verheij", "scopus_author_id"=>"6603727211"}, {"first_name"=>"Trinette", "last_name"=>"Van Vliet", "scopus_author_id"=>"7005493957"}, {"first_name"=>"Nicole H.P.", "last_name"=>"Cnubben", "scopus_author_id"=>"6603781623"}, {"first_name"=>"Age K.", "last_name"=>"Smilde", "scopus_author_id"=>"7005843679"}, {"first_name"=>"Jan", "last_name"=>"Van Der Greef", "scopus_author_id"=>"35839505500"}, {"first_name"=>"Ben", "last_name"=>"Van Ommen", "scopus_author_id"=>"55663202500"}, {"first_name"=>"Henk F.J.", "last_name"=>"Hendriks", "scopus_author_id"=>"7102230683"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84939895432", "doi"=>"10.1371/journal.pone.0004525", "isbn"=>"1932-6203 (Electronic)", "pmid"=>"19242536", "issn"=>"19326203", "scopus"=>"2-s2.0-84939895432", "pui"=>"618784099"}, "id"=>"9e1bc114-15f8-3613-bdbe-356330a44c54", "abstract"=>"BACKGROUND: The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism.\\n\\nMETHODOLOGY: To study the metabolic changes induced by a mild anti-inflammatory drug intervention, plasma metabolic profiling was applied in overweight human volunteers with elevated levels of the inflammatory plasma marker C-reactive protein. Liquid and gas chromatography mass spectrometric methods were used to detect high and low abundant plasma metabolites both in fasted conditions and during an oral glucose tolerance test. This is based on the concept that the resilience of the system can be assessed after perturbing a homeostatic situation.\\n\\nCONCLUSIONS: Metabolic changes were subtle and were only detected using metabolic profiling in combination with an oral glucose tolerance test. The repeated measurements during the oral glucose tolerance test increased statistical power, but the metabolic perturbation also revealed metabolites that respond differentially to the oral glucose tolerance test. Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test. The fact that this is an insulin sensitive pathway suggests that inflammatory modulation may alter insulin signaling in overweight men.", "link"=>"http://www.mendeley.com/research/metabolic-profiling-response-oral-glucose-tolerance-test-detects-subtle-metabolic-changes-5", "reader_count"=>44, "reader_count_by_academic_status"=>{"Researcher"=>15, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>2, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>4, "Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Researcher"=>15, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>2, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>4, "Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>5, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>21, "Medicine and Dentistry"=>9, "Psychology"=>1, "Chemistry"=>2, "Computer Science"=>1, "Economics, Econometrics and Finance"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Chemistry"=>{"Chemistry"=>2}, "Psychology"=>{"Psychology"=>1}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>21}, "Computer Science"=>{"Computer Science"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"Netherlands"=>1, "United States"=>1, "Ireland"=>1, "Italy"=>1, "Switzerland"=>1}, "group_count"=>1}

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  • {"files"=>["https://ndownloader.figshare.com/files/906578"], "description"=>"<p>A) glutathione mean response with standard error on day 9 corrected for concentrations on day 0 for subjects on placebo and diclofenac treatment. Glutathione showed a treatment difference only in the second part of the time course. B) Cysteinylglycine mean response with standard error on day 9 corrected for concentrations on day 0 for subjects on placebo and diclofenac treatment. Cysteinylglycine showed a treatment difference only in the second part of the time course. <i>Legend to </i><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004525#pone-0004525-g005\" target=\"_blank\"><i>Figure 5</i>:</a> Dashed line: Diclofenac treated subjects; Solid line: Placebo treated subjects.</p>", "links"=>[], "tags"=>["glutathione", "synthesis", "pathway", "intermediates", "ogtt"], "article_id"=>577026, "categories"=>["Genetics", "Medicine"], "users"=>["Suzan Wopereis", "Carina M. Rubingh", "Marjan J. van Erk", "Elwin R. Verheij", "Trinette van Vliet", "Nicole H. P. Cnubben", "Age K. Smilde", "Jan van der Greef", "Ben van Ommen", "Henk F. J. Hendriks"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004525.g005", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dynamic_response_of_glutathione_synthesis_pathway_intermediates_in_OGTT_time_course_/577026", "title"=>"Dynamic response of glutathione synthesis pathway intermediates in OGTT time course.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-02-26 01:57:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/906454"], "description"=>"<p>High levels of glucose inhibit and high levels of insulin activate glutathione synthesis via the enzyme γ-glutamylcysteine synthetase. <i>Legend to </i><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004525#pone-0004525-g004\" target=\"_blank\"><i>Figure 4</i>:</a> Connection arrows with color red represent inhibition and color green represent activation. Purple hexagons represent metabolites; purple hexagons with white star represent metabolites measured with one of the metabolic profiling platforms; orange symbols represent enzymes. Red arrows upwards indicate that higher plasma concentration levels were found in the diclofenac treated group in response to oral glucose tolerance test. Abbreviations: AA, amino acid; Cys-Gly, cysteinylglycine. These figures were created by using MapEditor version 2.1.0 (GeneGo Inc, St Joseph, MI).</p>", "links"=>[], "tags"=>["synthesis", "pathway", "glucose"], "article_id"=>576907, "categories"=>["Genetics", "Medicine"], "users"=>["Suzan Wopereis", "Carina M. Rubingh", "Marjan J. van Erk", "Elwin R. Verheij", "Trinette van Vliet", "Nicole H. P. Cnubben", "Age K. Smilde", "Jan van der Greef", "Ben van Ommen", "Henk F. J. Hendriks"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004525.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Glutathione_synthesis_pathway_and_its_connection_to_glucose_and_insulin_/576907", "title"=>"Glutathione synthesis pathway and its connection to glucose and insulin.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-02-26 01:55:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/906714"], "description"=>"<p>Characteristics of prostaglandin E2 and OGTT parameters (insulin and glucose) measured at start and end of treatments. AUC = area under the curve.</p>", "links"=>[], "tags"=>["prostaglandin", "e2", "ogtt", "parameters"], "article_id"=>577162, "categories"=>["Genetics", "Medicine"], "users"=>["Suzan Wopereis", "Carina M. Rubingh", "Marjan J. van Erk", "Elwin R. Verheij", "Trinette van Vliet", "Nicole H. P. Cnubben", "Age K. Smilde", "Jan van der Greef", "Ben van Ommen", "Henk F. J. Hendriks"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004525.t002", "stats"=>{"downloads"=>1, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characteristics_of_prostaglandin_E2_and_OGTT_parameters_insulin_and_glucose_measured_at_start_and_end_of_treatments_AUC_8202_8202_area_under_the_curve_/577162", "title"=>"Characteristics of prostaglandin E2 and OGTT parameters (insulin and glucose) measured at start and end of treatments. AUC = area under the curve.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-02-26 01:59:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/448568"], "description"=>"<div><h3>Background</h3><p>The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism.</p><h3>Methodology</h3><p>To study the metabolic changes induced by a mild anti-inflammatory drug intervention, plasma metabolic profiling was applied in overweight human volunteers with elevated levels of the inflammatory plasma marker C-reactive protein. Liquid and gas chromatography mass spectrometric methods were used to detect high and low abundant plasma metabolites both in fasted conditions and during an oral glucose tolerance test. This is based on the concept that the resilience of the system can be assessed after perturbing a homeostatic situation.</p><h3>Conclusions</h3><p>Metabolic changes were subtle and were only detected using metabolic profiling in combination with an oral glucose tolerance test. The repeated measurements during the oral glucose tolerance test increased statistical power, but the metabolic perturbation also revealed metabolites that respond differentially to the oral glucose tolerance test. Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test. The fact that this is an insulin sensitive pathway suggests that inflammatory modulation may alter insulin signaling in overweight men.</p></div>", "links"=>[], "tags"=>["metabolic", "profiling", "glucose", "detects", "changes"], "article_id"=>148395, "categories"=>["Genetics", "Medicine"], "users"=>["Suzan Wopereis", "Carina M. Rubingh", "Marjan J. van Erk", "Elwin R. Verheij", "Trinette van Vliet", "Nicole H. P. Cnubben", "Age K. Smilde", "Jan van der Greef", "Ben van Ommen", "Henk F. J. Hendriks"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004525", "stats"=>{"downloads"=>6, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Metabolic_Profiling_of_the_Response_to_an_Oral_Glucose_Tolerance_Test_Detects_Subtle_Metabolic_Changes/148395", "title"=>"Metabolic Profiling of the Response to an Oral Glucose Tolerance Test Detects Subtle Metabolic Changes", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-02-26 02:19:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/906750"], "description"=>"<p>The results of the different multivariate models are expressed as error rates.</p><p>Metabolite selection was only applied if the error rate of the original model of the complete dataset was below 35% and the dataset contained more than 50 metabolites. NA, not analyzed.</p>", "links"=>[], "tags"=>["metabolic", "profiling"], "article_id"=>577196, "categories"=>["Genetics", "Medicine"], "users"=>["Suzan Wopereis", "Carina M. Rubingh", "Marjan J. van Erk", "Elwin R. Verheij", "Trinette van Vliet", "Nicole H. P. Cnubben", "Age K. Smilde", "Jan van der Greef", "Ben van Ommen", "Henk F. J. Hendriks"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004525.t003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Multivariate_data_analysis_of_various_metabolic_profiling_datasets_/577196", "title"=>"Multivariate data analysis of various metabolic profiling datasets.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-02-26 01:59:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/906392"], "description"=>"<p>Day 0 insulin mean response with standard error is shown in OGTT time course for all subjects. Insulin concentrations show a maximum at ∼65 minutes after glucose intake.</p>", "links"=>[], "tags"=>["insulin", "ogtt"], "article_id"=>576846, "categories"=>["Genetics", "Medicine"], "users"=>["Suzan Wopereis", "Carina M. Rubingh", "Marjan J. van Erk", "Elwin R. Verheij", "Trinette van Vliet", "Nicole H. P. Cnubben", "Age K. Smilde", "Jan van der Greef", "Ben van Ommen", "Henk F. J. Hendriks"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004525.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Day_0_insulin_response_in_OGTT_time_course_/576846", "title"=>"Day 0 insulin response in OGTT time course.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-02-26 01:54:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/906841"], "description"=>"<p>Per analytical platform the metabolites are ranked according to their importance to the model, thus uric acid and isoleucine contributed most in the discrimination between the treatment groups.</p><p>Only identified metabolites are shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004525#pone-0004525-t004\" target=\"_blank\">Table 4</a>. The column ‘response type’ refers to <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004525#pone-0004525-g002\" target=\"_blank\">Figure 2</a>; metabolites with response type A showed a treatment difference over the whole time course and metabolites with response type B showed a treatment difference only in the second part of the time course (a response of the metabolite in the placebo group, whereas no change in the diclofenac treated group). For metabolites with response type B the mean is calculated over the time points with a treatment difference.</p>", "links"=>[], "tags"=>["discriminating", "metabolite", "ogtt"], "article_id"=>577295, "categories"=>["Genetics", "Medicine"], "users"=>["Suzan Wopereis", "Carina M. Rubingh", "Marjan J. van Erk", "Elwin R. Verheij", "Trinette van Vliet", "Nicole H. P. Cnubben", "Age K. Smilde", "Jan van der Greef", "Ben van Ommen", "Henk F. J. Hendriks"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004525.t004", "stats"=>{"downloads"=>4, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overview_of_most_discriminating_metabolites_their_treatment_effect_and_their_metabolite_response_in_the_OGTT_time_course_/577295", "title"=>"Overview of most discriminating metabolites, their treatment effect and their metabolite response in the OGTT time course.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-02-26 02:01:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/906654"], "description"=>"<p>Day 0 glutathione mean response with standard error is shown in OGTT time course for all subjects. Glutathione showed declined concentrations in the first part of the time course with a minimum concentration at 60 minutes after glucose intake. In the second part of the time course concentrations increase again.</p>", "links"=>[], "tags"=>["glutathione", "ogtt"], "article_id"=>577105, "categories"=>["Genetics", "Medicine"], "users"=>["Suzan Wopereis", "Carina M. Rubingh", "Marjan J. van Erk", "Elwin R. Verheij", "Trinette van Vliet", "Nicole H. P. Cnubben", "Age K. Smilde", "Jan van der Greef", "Ben van Ommen", "Henk F. J. Hendriks"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004525.g006", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Day_0_glutathione_response_in_OGTT_time_course_/577105", "title"=>"Day 0 glutathione response in OGTT time course.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-02-26 01:58:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/906251"], "description"=>"<p>To determine metabolites that were modulated by the diclofenac treatment the following multivariate data comparisons were performed to identify metabolites that were modulated by the diclofenac treatment: a) PLS-DA on metabolic profiling data from day 9 subtracted by metabolic profiling data from day 0, on fasted plasma samples; b) n-PLS-DA on metabolic profiling data from day 0, 2, 4, 7 and 9, on fasted plasma samples; c) n-PLS-DA on metabolic profiling data from day 9 subtracted by metabolic profiling data from day 0, using the fasted plasma samples and the samples after glucose administration, thus metabolic profiling data on 0, 15, 30, 45, 60, 90, 120 and 180 minutes after glucose administration. The multivariate data comparisons from a-c were performed per metabolite platform, thus multivariate models were created for GC-MS global, LC-MS polar, LC-MS lipids and LC-MS free fatty acids data.</p>", "links"=>[], "tags"=>["points", "metabolome", "was", "multivariate"], "article_id"=>576697, "categories"=>["Genetics", "Medicine"], "users"=>["Suzan Wopereis", "Carina M. Rubingh", "Marjan J. van Erk", "Elwin R. Verheij", "Trinette van Vliet", "Nicole H. P. Cnubben", "Age K. Smilde", "Jan van der Greef", "Ben van Ommen", "Henk F. J. Hendriks"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004525.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overview_of_study_design_time_points_at_which_metabolome_was_measured_and_multivariate_data_analyses_/576697", "title"=>"Overview of study design, time points at which metabolome was measured and multivariate data analyses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-02-26 01:51:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/906317"], "description"=>"<p>A) for the metabolite isoleucine that contributes to treatment differences over the whole time course and B) for the metabolite glycine that contributes to treatment differences only in the second part of the time course. <i>Legend to </i><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004525#pone-0004525-g002\" target=\"_blank\"><i>Figure 2</i>:</a> Dashed line: Diclofenac treated subjects; Solid line: Placebo treated subjects.</p>", "links"=>[], "tags"=>["metabolite", "corrected", "concentrations", "subjects", "placebo", "diclofenac"], "article_id"=>576761, "categories"=>["Genetics", "Medicine"], "users"=>["Suzan Wopereis", "Carina M. Rubingh", "Marjan J. van Erk", "Elwin R. Verheij", "Trinette van Vliet", "Nicole H. P. Cnubben", "Age K. Smilde", "Jan van der Greef", "Ben van Ommen", "Henk F. J. Hendriks"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004525.g002", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_OGTT_time_course_mean_metabolite_response_with_standard_error_on_day_9_corrected_for_concentrations_on_day_0_for_subjects_on_placebo_and_diclofenac_treatment_/576761", "title"=>"OGTT time course mean metabolite response with standard error on day 9 corrected for concentrations on day 0 for subjects on placebo and diclofenac treatment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-02-26 01:52:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/906788"], "description"=>"<p>Demographic data of subjects that completed the study (n = 19) at screening; mean±SD (range).</p>", "links"=>[], "tags"=>["subjects", "completed"], "article_id"=>577242, "categories"=>["Genetics", "Medicine"], "users"=>["Suzan Wopereis", "Carina M. Rubingh", "Marjan J. van Erk", "Elwin R. Verheij", "Trinette van Vliet", "Nicole H. P. Cnubben", "Age K. Smilde", "Jan van der Greef", "Ben van Ommen", "Henk F. J. Hendriks"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004525.t001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographic_data_of_subjects_that_completed_the_study_n_8202_8202_19_at_screening_mean_177_SD_range_/577242", "title"=>"Demographic data of subjects that completed the study (n = 19) at screening; mean±SD (range).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-02-26 02:00:42"}

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Relative Metric

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