#METABOLOMICS WORKBENCH hormel101_20180409_153445 DATATRACK_ID:1360 STUDY_ID:ST000947 ANALYSIS_ID:AN001554 PROJECT_ID:PR000652 VERSION 1 CREATED_ON April 10, 2018, 10:17 pm #PROJECT PR:PROJECT_TITLE Mayo Pilot and Feasibility: Mechanisms for Insulin Resistance in Polycystic PR:PROJECT_TITLE Ovary Syndrome PR:PROJECT_SUMMARY Polycystic Ovary Syndrome (PCOS), a condition of androgen excess, infrequent PR:PROJECT_SUMMARY ovulation, and insulin resistance is the most common endocrine disorder among PR:PROJECT_SUMMARY premenopausal women. Little is known about the exact mechanisms of insulin PR:PROJECT_SUMMARY resistance in PCOS and how metformin can improve insulin sensitivity, increase PR:PROJECT_SUMMARY the frequency of ovulation and lower androgens in PCOS. Preliminary data from PR:PROJECT_SUMMARY metabolomic analyses of amino acids demonstrate increased concentrations of PR:PROJECT_SUMMARY lysine and its metabolite, α-aminoadipic acid (AAA), in PCOS versus obese PR:PROJECT_SUMMARY controls. Interestingly, greater AAA concentrations predicted the development of PR:PROJECT_SUMMARY type 2 diabetes in the Framingham epidemiologic cohort, experimentally lowers PR:PROJECT_SUMMARY glucose in animal models and increases insulin secretion in vitro. To date, the PR:PROJECT_SUMMARY mechanism for increased circulating concentrations of lysine and AAA in PR:PROJECT_SUMMARY insulin-resistant individuals is not known. Building upon these findings, we PR:PROJECT_SUMMARY have initiated a project to simultaneously study lysine and AAA kinetics for the PR:PROJECT_SUMMARY first time in insulin-resistant individuals using stable isotope tracer PR:PROJECT_SUMMARY methodology. We will evaluate: 1) whether lysine and AAA kinetics are altered in PR:PROJECT_SUMMARY PCOS versus healthy controls; 2) the effect of hyperinsulinemia on lysine and PR:PROJECT_SUMMARY AAA kinetics in PCOS versus controls; 3) whether treatment to improve insulin PR:PROJECT_SUMMARY sensitivity changes lysine and AAA kinetics in PCOS. The long-term goal is to PR:PROJECT_SUMMARY target pathways for the treatment of PCOS and the prevention of type 2 diabetes PR:PROJECT_SUMMARY in PCOS and other insulin-resistant individuals at greater risk for type 2 PR:PROJECT_SUMMARY diabetes. PR:INSTITUTE Mayo Clinic PR:LAST_NAME Chang PR:FIRST_NAME Alice PR:ADDRESS 200 First St. SW, Rochester, Minnesota, 55905, USA PR:EMAIL Chang.Alice1@mayo.edu PR:PHONE 507-286-0505 #STUDY ST:STUDY_TITLE Mechanisms for Insulin Resistance in Polycystic Ovary Syndrome: aminoadipic ST:STUDY_TITLE acid, lysine concentrations, and enrichment (part I) ST:STUDY_SUMMARY "To determine whether altered lysine and α-aminoadipic acid (AAA) kinetics ST:STUDY_SUMMARY explain previous observations of increased lysine and AAA concentrations in PCOS ST:STUDY_SUMMARY compared to controls, as measured by baseline lysine and AAA flux in PCOS versus ST:STUDY_SUMMARY healthy controls using [α-15N]-lysine and [13C]-AAA stable isotope tracers as ST:STUDY_SUMMARY well as by comparing the conversion of [α-15N]-lysine to [15N]-AAA. To evaluate ST:STUDY_SUMMARY how hyperinsulinemia affects lysine and AAA kinetics. Changes in lysine and AAA ST:STUDY_SUMMARY flux during a hyperinsulinemic-euglycemic clamp will be evaluated in healthy ST:STUDY_SUMMARY controls and compared to the baseline changes in lysine and AAA flux in PCOS." ST:INSTITUTE Mayo Clinic ST:LAST_NAME Chang ST:FIRST_NAME Al ST:ADDRESS 200 First St. SW, Rochester, Minnesota, 55905, USA ST:EMAIL Chang.Alice1@mayo.edu ST:PHONE 507-286-0505 #SUBJECT SU:SUBJECT_TYPE Human SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS 7744 ms6032-1 Time point:baseline | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-2 Time point:-60 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-3 Time point:-45 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-4 Time point:-30 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-5 Time point:-15 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-6 Time point:60 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-7 Time point:120 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-8 Time point:135 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-9 Time point:150 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-10 Time point:165 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-11 Time point:180 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-1 Time point:baseline | Group:PCOS Date of study=11/14/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-2 Time point:-60 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-3 Time point:-45 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-4 Time point:-30 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-5 Time point:-15 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-6 Time point:60 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-7 Time point:120 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-8 Time point:135 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-9 Time point:150 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-10 Time point:165 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-11 Time point:180 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6087-1 Time point:baseline | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-2 Time point:-60 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-3 Time point:-45 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-4 Time point:-30 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-5 Time point:-15 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-6 Time point:60 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-7 Time point:120 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-8 Time point:135 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-9 Time point:150 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-10 Time point:165 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-11 Time point:180 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-1 Time point:baseline | Group:control Date of study=3/22/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-2 Time point:-60 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-3 Time point:-45 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-4 Time point:-30 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-5 Time point:-15 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-6 Time point:60 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-7 Time point:120 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-8 Time point:135 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-9 Time point:150 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-10 Time point:165 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-11 Time point:180 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-1 Time point:baseline | Group:control Date of study=5/11/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-2 Time point:-60 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-3 Time point:-45 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-4 Time point:-30 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-5 Time point:-15 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-6 Time point:60 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-7 Time point:120 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-8 Time point:135 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-9 Time point:150 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-10 Time point:165 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-11 Time point:180 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-1 Time point:baseline | Group:PCOS Date of study=5/3/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-2 Time point:-60 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-3 Time point:-45 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-4 Time point:-30 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-5 Time point:-15 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-6 Time point:60 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-7 Time point:120 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-8 Time point:135 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-9 Time point:150 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-10 Time point:165 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-11 Time point:180 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-1 Time point:baseline | Group:control Date of study=3/282016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-2 Time point:-60 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-3 Time point:-45 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-4 Time point:-30 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-5 Time point:-15 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-6 Time point:60 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-7 Time point:120 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-8 Time point:135 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-9 Time point:150 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-10 Time point:165 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-11 Time point:180 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-1 Time point:baseline | Group:control Date of study=5/26/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-2 Time point:-60 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-3 Time point:-45 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-4 Time point:-30 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-5 Time point:-15 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-6 Time point:60 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-7 Time point:120 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-8 Time point:135 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-9 Time point:150 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-10 Time point:165 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-11 Time point:180 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-1 Time point:baseline | Group:PCOS Date of study=1/28/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-2 Time point:-60 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-3 Time point:-45 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-4 Time point:-30 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-5 Time point:-15 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-6 Time point:60 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-7 Time point:120 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-8 Time point:135 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-9 Time point:150 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-10 Time point:165 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-11 Time point:180 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-1 Time point:baseline | Group:control Date of study=3/6/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-2 Time point:-60 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-3 Time point:-45 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-4 Time point:-30 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-5 Time point:-15 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-6 Time point:60 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-7 Time point:120 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-8 Time point:135 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-9 Time point:150 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-10 Time point:165 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-11 Time point:180 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 7725 ms6186-1 Time point:baseline | Group:PCOS Date of study=3/10/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-2 Time point:-60 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-3 Time point:-45 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-4 Time point:-30 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-5 Time point:-15 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-6 Time point:60 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-7 Time point:120 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-8 Time point:135 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-9 Time point:150 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-10 Time point:165 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-11 Time point:180 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 4620 ms6187-1 Time point:baseline | Group:PCOS Date of study=4/21/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-2 Time point:-60 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-3 Time point:-45 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-4 Time point:-30 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-5 Time point:-15 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-6 Time point:60 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-7 Time point:120 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-8 Time point:135 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-9 Time point:150 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-10 Time point:165 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-11 Time point:180 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-1 Time point:baseline | Group:PCOS Date of study=1/12/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-2 Time point:-60 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-3 Time point:-45 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-4 Time point:-30 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-5 Time point:-15 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-6 Time point:60 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-7 Time point:120 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-8 Time point:135 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-9 Time point:150 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-10 Time point:165 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-11 Time point:180 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-1 Time point:baseline | Group:control Date of study=2/16/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-2 Time point:-60 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-3 Time point:-45 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-4 Time point:-30 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-5 Time point:-15 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-6 Time point:60 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-7 Time point:120 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-8 Time point:135 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-9 Time point:150 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-10 Time point:165 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-11 Time point:180 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-1 Time point:baseline | Group:control Date of study=12/13/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-2 Time point:-60 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-3 Time point:-45 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-4 Time point:-30 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-5 Time point:-15 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-6 Time point:60 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-7 Time point:120 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-8 Time point:135 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-9 Time point:150 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-10 Time point:165 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-11 Time point:180 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-1 Time point:baseline | Group:control Date of study=1/23/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-2 Time point:-60 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-3 Time point:-45 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-4 Time point:-30 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-5 Time point:-15 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-6 Time point:60 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-7 Time point:120 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-8 Time point:135 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-9 Time point:150 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-10 Time point:165 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-11 Time point:180 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-1 Time point:baseline | Group:PCOS Date of study=11/16/2015 SUBJECT_SAMPLE_FACTORS 2780 ms6091-2 Time point:-60 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-3 Time point:-45 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-4 Time point:-30 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-5 Time point:-15 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-6 Time point:60 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-7 Time point:120 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-8 Time point:135 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-9 Time point:150 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-10 Time point:165 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-11 Time point:180 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-1 Time point:baseline | Group:PCOS Date of study=2/22/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-2 Time point:-60 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-3 Time point:-45 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-4 Time point:-30 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-5 Time point:-15 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-6 Time point:60 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-7 Time point:120 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-8 Time point:135 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-9 Time point:150 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-10 Time point:165 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-11 Time point:180 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-1 Time point:baseline | Group:control Date of study=1/18/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-2 Time point:-60 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-3 Time point:-45 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-4 Time point:-30 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-5 Time point:-15 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-6 Time point:60 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-7 Time point:120 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-8 Time point:135 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-9 Time point:150 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-10 Time point:165 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-11 Time point:180 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8999 ms6042-1 Time point:baseline | Group:PCOS Date of study=12/15/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-2 Time point:-60 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-3 Time point:-45 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-4 Time point:-30 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-5 Time point:-15 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-6 Time point:60 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-7 Time point:120 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-8 Time point:135 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-9 Time point:150 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-10 Time point:165 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-11 Time point:180 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-1 Time point:baseline | Group:PCOS Date of study=12/18/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-2 Time point:-60 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-3 Time point:-45 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-4 Time point:-30 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-5 Time point:-15 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-6 Time point:60 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-7 Time point:120 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-8 Time point:135 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-9 Time point:150 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-10 Time point:165 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-11 Time point:180 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7534 ms6035-1 Time point:baseline | Group:control Date of study=1/25/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-2 Time point:-60 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-3 Time point:-45 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-4 Time point:-30 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-5 Time point:-15 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-6 Time point:60 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-7 Time point:120 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-8 Time point:135 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-9 Time point:150 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-10 Time point:165 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-11 Time point:180 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 3463 ms6038-1 Time point:baseline | Group:PCOS Date of study=12/1/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-2 Time point:-60 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-3 Time point:-45 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-4 Time point:-30 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-5 Time point:-15 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-6 Time point:60 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-7 Time point:120 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-8 Time point:135 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-9 Time point:150 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-10 Time point:165 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-11 Time point:180 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 6454 ms6101-1 Time point:baseline | Group:PCOS Date of study=2/18/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-2 Time point:-60 | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-3 Time point:-45 | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-4 Time point:-30 | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-5 Time point:-15 | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-6 Time point:60 | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-7 Time point:120 | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-8 Time point:135 | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-9 Time point:150 | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-10 Time point:165 | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-11 Time point:180 | Group:PCOS Date of study=2/19/2016 #COLLECTION CO:COLLECTION_SUMMARY We will perform a hyperinsulinemic-euglycemic clamp as previously described CO:COLLECTION_SUMMARY except that in this current proposal we will perform the study for 3 hours.(36) CO:COLLECTION_SUMMARY The goal for this infusion is to assess the effect of hyperinsulinemia on lysine CO:COLLECTION_SUMMARY and AAA kinetics and whether metformin changes the effect of hyperinsulinemia. CO:COLLECTION_SUMMARY We will collect samples every 10 min for glucose. 40% dextrose will be infused CO:COLLECTION_SUMMARY at a variable rate during the clamp to maintain euglycemia.(36) During the last CO:COLLECTION_SUMMARY hour of the clamp, 5 blood samples will be drawn for measurement of stable CO:COLLECTION_SUMMARY isotope tracer enrichment and amino acid concentrations. CO:SAMPLE_TYPE Blood (plasma) #TREATMENT TR:TREATMENT_SUMMARY "Ten women with PCOS will receive metformin therapy, and ten women will be TR:TREATMENT_SUMMARY randomized to receive no therapy and undergo the same repeat visits after 3 TR:TREATMENT_SUMMARY months. Ten age-matched women without PCOS with a BMI < 25 will be recruited as TR:TREATMENT_SUMMARY the control group for the baseline visit. Aside from criteria that they do not TR:TREATMENT_SUMMARY have PCOS and have a BMI < 25, this control group will have the same inclusion TR:TREATMENT_SUMMARY and exclusion criteria below. They will not receive metformin and will not TR:TREATMENT_SUMMARY return for repeat visits after 3 months. Metformin therapy: Previous studies TR:TREATMENT_SUMMARY with metformin demonstrated improvement in insulin sensitivity as early as 3 TR:TREATMENT_SUMMARY months with 1000 mg daily.(5, 33, 34) Metformin will be initiated with 500 mg TR:TREATMENT_SUMMARY extended-release tablet daily for one week, 1000 mg daily for one week and then TR:TREATMENT_SUMMARY 1500 mg daily. Visits 4 and 5 will be conducted three months after full dose is TR:TREATMENT_SUMMARY achieved. Oral glucose tolerance test: After 2 baseline fasting samples, 75 g of TR:TREATMENT_SUMMARY oral dextrose will be ingested with blood samples will be drawn at 10’, 20’, TR:TREATMENT_SUMMARY 30’, 60’, 90’, 120’, 150’and 180’ for measurement of glucose, TR:TREATMENT_SUMMARY insulin, c-peptide. Insulin sensitivity will be calculated using the oral TR:TREATMENT_SUMMARY glucose minimal model. Stable isotope tracer infusions (Figure 5): Three days TR:TREATMENT_SUMMARY prior to the tracer study, the participants will be placed on a TR:TREATMENT_SUMMARY weight-maintaining diet consisting of 50% carbohydrates, 20% protein, and 30% TR:TREATMENT_SUMMARY fats. Fat free mass (FFM) measured by dual-energy x-ray absorptiometry will be TR:TREATMENT_SUMMARY used for dose calculations of the stable isotope tracers and insulin infusions TR:TREATMENT_SUMMARY for the hyperinsulinemic-euglycemic clamp. A priming bolus dose of TR:TREATMENT_SUMMARY L-[α-15N]-lysine, 3 to 5 μmol/kg FFM, will be given at the start of a 3 hour TR:TREATMENT_SUMMARY infusion of 3 to 5 μmol/kg FFM/hr to achieve a plateau as previously TR:TREATMENT_SUMMARY described.(29) At the same time, a priming bolus of 1 to 2 μmol/kg FFM TR:TREATMENT_SUMMARY L-[1-13C]-2-aminoadipic acid will be given followed by infusion of 1 to 2 TR:TREATMENT_SUMMARY μmol/kg/hr based on prior study.(30) A retrograde hand intravenous line will be TR:TREATMENT_SUMMARY placed with the hand placed in a warm box maintained at 140°F to obtain TR:TREATMENT_SUMMARY arterialized venous blood samples for measurement of lysine and AAA TR:TREATMENT_SUMMARY concentrations and stable isotopic enrichment at steady state and during the TR:TREATMENT_SUMMARY clamp. Hyperinsulinemic-euglycemic clamp: We will perform a TR:TREATMENT_SUMMARY hyperinsulinemic-euglycemic clamp as previously described except that in this TR:TREATMENT_SUMMARY current proposal we will perform the study for 3 hours.(36) The goal for this TR:TREATMENT_SUMMARY infusion is to assess the effect of hyperinsulinemia on lysine and AAA kinetics TR:TREATMENT_SUMMARY and whether metformin changes the effect of hyperinsulinemia. We will collect TR:TREATMENT_SUMMARY samples every 10 min for glucose. 40% dextrose will be infused at a variable TR:TREATMENT_SUMMARY rate during the clamp to maintain euglycemia.(36) During the last hour of the TR:TREATMENT_SUMMARY clamp, 5 blood samples will be drawn for measurement of stable isotope tracer TR:TREATMENT_SUMMARY enrichment and amino acid concentrations. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Plasma lysine and AAA concentrations and isotopic enrichment will be analyzed as SP:SAMPLEPREP_SUMMARY previous described via a Thermo Fisher Q Exactive plus mass spectrometer coupled SP:SAMPLEPREP_SUMMARY with a Dionex UltiMate 3000 Binary RSLC liquid chromatograph. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE Reversed phase MS:INSTRUMENT_NAME Thermo Q Exactive Plus Orbitrap CH:COLUMN_NAME Zorbax Extended C18 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Plus Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS uM #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS uM MS_METABOLITE_DATA_START Samples ms6032-1 ms6032-2 ms6032-3 ms6032-4 ms6032-5 ms6032-6 ms6032-7 ms6032-8 ms6032-9 ms6032-10 ms6032-11 ms6039-1 ms6039-2 ms6039-3 ms6039-4 ms6039-5 ms6039-6 ms6039-7 ms6039-8 ms6039-9 ms6039-10 ms6039-11 ms6087-1 ms6087-2 ms6087-3 ms6087-4 ms6087-5 ms6087-6 ms6087-7 ms6087-8 ms6087-9 ms6087-10 ms6087-11 ms6184-1 ms6184-2 ms6184-3 ms6184-4 ms6184-5 ms6184-6 ms6184-7 ms6184-8 ms6184-9 ms6184-10 ms6184-11 ms6185-1 ms6185-2 ms6185-3 ms6185-4 ms6185-5 ms6185-6 ms6185-7 ms6185-8 ms6185-9 ms6185-10 ms6185-11 ms6189-1 ms6189-2 ms6189-3 ms6189-4 ms6189-5 ms6189-6 ms6189-7 ms6189-8 ms6189-9 ms6189-10 ms6189-11 ms6188-1 ms6188-2 ms6188-3 ms6188-4 ms6188-5 ms6188-6 ms6188-7 ms6188-8 ms6188-9 ms6188-10 ms6188-11 ms6243-1 ms6243-2 ms6243-3 ms6243-4 ms6243-5 ms6243-6 ms6243-7 ms6243-8 ms6243-9 ms6243-10 ms6243-11 ms6275-1 ms6275-2 ms6275-3 ms6275-4 ms6275-5 ms6275-6 ms6275-7 ms6275-8 ms6275-9 ms6275-10 ms6275-11 ms6183-1 ms6183-2 ms6183-3 ms6183-4 ms6183-5 ms6183-6 ms6183-7 ms6183-8 ms6183-9 ms6183-10 ms6183-11 ms6186-1 ms6186-2 ms6186-3 ms6186-4 ms6186-5 ms6186-6 ms6186-7 ms6186-8 ms6186-9 ms6186-10 ms6186-11 ms6187-1 ms6187-2 ms6187-3 ms6187-4 ms6187-5 ms6187-6 ms6187-7 ms6187-8 ms6187-9 ms6187-10 ms6187-11 ms6100-1 ms6100-2 ms6100-3 ms6100-4 ms6100-5 ms6100-6 ms6100-7 ms6100-8 ms6100-9 ms6100-10 ms6100-11 ms6102-1 ms6102-2 ms6102-3 ms6102-4 ms6102-5 ms6102-6 ms6102-7 ms6102-8 ms6102-9 ms6102-10 ms6102-11 ms6182-1 ms6182-2 ms6182-3 ms6182-4 ms6182-5 ms6182-6 ms6182-7 ms6182-8 ms6182-9 ms6182-10 ms6182-11 ms6034-1 ms6034-2 ms6034-3 ms6034-4 ms6034-5 ms6034-6 ms6034-7 ms6034-8 ms6034-9 ms6034-10 ms6034-11 ms6091-1 ms6091-2 ms6091-3 ms6091-4 ms6091-5 ms6091-6 ms6091-7 ms6091-8 ms6091-9 ms6091-10 ms6091-11 ms6098-1 ms6098-2 ms6098-3 ms6098-4 ms6098-5 ms6098-6 ms6098-7 ms6098-8 ms6098-9 ms6098-10 ms6098-11 ms6036-1 ms6036-2 ms6036-3 ms6036-4 ms6036-5 ms6036-6 ms6036-7 ms6036-8 ms6036-9 ms6036-10 ms6036-11 ms6042-1 ms6042-2 ms6042-3 ms6042-4 ms6042-5 ms6042-6 ms6042-7 ms6042-8 ms6042-9 ms6042-10 ms6042-11 ms6099-1 ms6099-2 ms6099-3 ms6099-4 ms6099-5 ms6099-6 ms6099-7 ms6099-8 ms6099-9 ms6099-10 ms6099-11 ms6035-1 ms6035-2 ms6035-3 ms6035-4 ms6035-5 ms6035-6 ms6035-7 ms6035-8 ms6035-9 ms6035-10 ms6035-11 ms6038-1 ms6038-2 ms6038-3 ms6038-4 ms6038-5 ms6038-6 ms6038-7 ms6038-8 ms6038-9 ms6038-10 ms6038-11 ms6101-1 ms6101-2 ms6101-3 ms6101-4 ms6101-5 ms6101-6 ms6101-7 ms6101-8 ms6101-9 ms6101-10 ms6101-11 Factors Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS aminoadipic 0.796348623 0.604570746 0.672376869 0.621887764 0.617913005 0.537768957 0.385995337 0.427876987 0.458561028 0.422738743 0.439988937 0.991204736 0.854154032 0.795969446 0.822008498 0.87377195 0.759062279 0.643202218 0.688464364 0.773270632 0.73400765 0.752695578 1.840604462 0.913558589 1.235268613 0.938289965 0.76768043 1.138267549 0.777074636 0.827404535 0.829747292 0.8001268 0.762958849 0.920061448 0.62479098 0.724974718 0.631924401 0.727648434 0.649364028 0.703856376 0.658278676 0.634326489 0.601020045 0.610416305 0.949099181 0.647208025 0.725787641 0.729824438 0.69179728 0.537856306 0.464091291 0.551876195 0.529687538 0.527280744 0.479915564 1.014967432 1.010355299 1.0993595 0.952976659 1.038375589 0.886430105 0.714939693 0.799104616 0.74422836 0.844481832 0.669772077 1.071189393 0.894442391 0.903387259 0.887187801 0.898341098 0.737159165 0.725107432 0.747131279 0.746998488 0.780858165 0.751341717 0.677565653 0.668865382 0.674667212 0.67141215 0.730936011 0.691328592 0.525733759 0.6074677 0.6327044 0.570334317 0.61622037 1.123117187 1.183720563 1.004066963 1.188586437 1.314239089 1.040480263 0.9458819 0.98839828 0.962521638 0.97490212 0.985635925 1.035727611 0.538984766 0.608167241 0.522797766 0.531897915 0.501004913 0.442379004 0.453407219 0.477157429 0.439631582 0.451381797 1.843419205 0.987028705 0.966921009 0.95988011 0.984540145 0.922798351 0.862319834 0.846878919 0.834478084 0.821167026 0.874215437 2.00910533 1.207550514 1.129586626 0.957867343 1.072927064 0.730689834 0.641617059 0.566761507 0.703398651 0.661484048 0.734551476 0.73525948 0.469497998 0.565447713 0.511197093 0.530293285 0.545587161 0.442868352 0.491789255 0.486451288 0.452878622 0.414890643 1.498435801 1.059607443 1.027136328 1.112322875 0.977313802 0.888689994 0.749966134 0.857904564 0.800514571 0.75531117 0.630696146 0.480307002 0.439720876 0.462550342 0.494318549 0.460362648 0.458831457 0.426135442 0.426095035 0.459008564 0.381508698 0.428449403 0.730527295 0.496465817 0.617696346 0.606855583 0.592497465 0.523824441 0.4359921 0.463873194 0.511983251 0.560860626 0.490130742 1.13834371 1.125206776 1.081010653 1.047141191 1.112171827 0.867599924 0.740627048 0.827529202 0.769744566 0.785981458 0.945949562 0.786922014 0.949436108 0.857549749 0.964113688 0.997211638 0.88403397 0.826462202 0.853739817 0.716340061 0.80531341 0.797994769 1.001109026 0.717346201 0.751881137 0.933907136 0.902004478 0.630211508 0.644538592 0.591129095 0.589644882 0.562438734 0.549171731 1.06108067 0.849810873 0.95659327 1.044703265 0.975841423 1.437895841 0.693929686 0.742120466 0.766288331 0.733354655 0.772107454 0.913314859 0.676768541 0.766368946 0.774691472 0.752027609 0.740467796 0.655687421 0.632202267 0.806351442 0.723313744 1.03494968 0.542780452 0.364439274 0.388040649 0.408110814 0.435302612 0.351266938 0.320531022 0.331398433 0.328802693 0.359567398 0.398607211 0.951180735 0.80756324 0.769363439 0.731059607 0.664876157 0.744068543 0.558247778 0.523892284 0.550174452 0.503926422 0.573329551 0.678924948 0.409422099 0.473547175 0.4417022 0.490483534 0.333965992 0.430175348 0.400931418 0.35161662 0.414678813 0.420628396 Lysine 149.5377529 117.9064001 122.5737378 120.5620532 111.7072986 98.29875289 93.36273611 91.79254216 91.66831734 90.45844285 98.15333098 161.0064174 162.3173526 174.5889869 166.3746924 159.648098 152.2171483 136.9231115 146.9545379 157.6357425 149.374604 147.4914673 249.8976348 175.7549533 184.8437705 168.4614102 175.928 183.5173475 166.1992467 168.3259592 164.100999 170.2130073 160.2691045 157.2226796 132.0091442 135.0672571 137.4921514 194.181425 139.309324 122.038638 136.2563781 135.0138777 133.4063117 129.9317204 269.8837932 166.6484115 172.1792155 172.4914372 167.5662598 130.173713 114.2159288 147.6203244 117.5603816 122.9840458 111.4540595 162.6382342 174.4122251 195.0150993 182.3710262 182.0862126 164.0327947 175.6653829 179.9787242 181.4087156 175.8998304 154.0460212 233.9430023 208.9615783 215.4735566 196.9130175 199.3601604 190.5205959 195.7716597 199.1284988 198.8807605 209.3318868 181.9514165 199.7487283 168.3117795 160.4916746 161.3529875 161.2066384 166.9230955 142.9851964 162.6908797 155.2701159 153.2755893 148.3563846 189.5773393 226.6723017 175.4888635 221.8727512 215.1606539 200.1582713 175.7053849 197.963596 184.9354817 192.8955376 189.6698835 171.4928085 142.5789184 152.7515088 157.7551663 131.0643829 122.0960264 121.0217718 121.302109 137.5768559 130.688678 130.8932365 288.1799201 205.1478765 208.4012071 195.719947 194.4355227 178.5198421 173.872975 164.9627836 177.1890491 168.324518 170.5304878 312.3078224 263.4078113 239.2777259 221.6098959 245.75333 147.7117935 154.4971132 134.7554411 153.1040371 159.6145546 151.660076 157.0377327 152.7724311 152.9166093 149.6306084 160.3903206 159.0478333 132.1515136 145.9946824 140.0361849 125.6737572 124.0282636 183.3252846 150.1515449 148.5682971 146.8634681 143.4223189 131.0242765 119.7478576 135.0273892 128.90442 116.0929378 98.02609493 110.9399815 139.7987904 130.2279939 136.9631633 129.1155705 121.2986671 118.3225341 112.2439791 114.3217371 107.5648812 112.5838133 235.0516861 170.0338899 164.0537739 155.583044 155.2704437 144.8778302 131.2675091 138.9350946 135.2913719 137.4506561 134.5358766 272.6554991 213.5202132 214.7632326 194.5914671 206.1168164 178.4508469 170.9154406 175.6496605 179.2101086 161.7794197 188.8405411 198.3589186 205.7323669 202.5242589 213.3546528 196.8664401 203.0880608 190.1637387 183.5076516 188.5326847 187.8042684 172.5239615 220.0497013 157.4296064 159.450557 154.9649172 171.249989 143.5301715 142.0979694 146.227152 143.7447363 136.283229 117.3368473 268.2620733 234.2722199 222.4450242 236.6058678 235.2444041 229.1832831 209.6360445 217.4643081 219.4419255 219.4364106 216.7519543 255.6287773 190.3639452 192.9273175 188.8891048 187.2133016 165.1593941 165.2564077 157.7702704 165.458329 178.7492423 175.846359 131.1976883 137.3494181 135.5927176 134.6259428 144.5988827 112.8383996 107.87097 110.6800278 111.0024921 112.1949335 108.7901802 254.3027138 219.7497552 203.0193943 190.8538147 203.7134366 199.9627726 180.7018149 176.0771932 172.0806703 182.0096582 182.3281344 200.2888253 113.1422894 130.1528003 134.8066294 132.1084824 98.05126955 116.3864056 110.4243381 111.5182732 118.3528926 110.0925443 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name aminoadipic Lysine METABOLITES_END #END