Summary of Study ST000383

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR000300. The data can be accessed directly via it's Project DOI: 10.21228/M88C86 This work is supported by NIH grant, U2C- DK119886.


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Study IDST000383
Study TitlePlasma Metabolomic Profiles Reflective of Glucose Homeostasis in Non-Diabetic and Type 2 Diabetic Obese African-American Women
Study SummaryInsulin resistance progressing to type 2 diabetes mellitus (T2DM) is marked by a broad perturbation of macronutrient intermediary metabolism. Understanding the biochemical networks that underlie metabolic homeostasis and how they associate with insulin action will help unravel diabetes etiology and should foster discovery of new biomarkers of disease risk and severity. We examined differences in plasma concentrations of >350 metabolites in fasted obese T2DM vs. obese non-diabetic African-American women, and utilized principal components analysis to identify 158 metabolite components that strongly correlated with fasting HbA1c over a broad range of the latter (r?=??0.631; p<0.0001). In addition to many unidentified small molecules, specific metabolites that were increased significantly in T2DM subjects included certain amino acids and their derivatives (i.e., leucine, 2-ketoisocaproate, valine, cystine, histidine), 2-hydroxybutanoate, long-chain fatty acids, and carbohydrate derivatives. Leucine and valine concentrations rose with increasing HbA1c, and significantly correlated with plasma acetylcarnitine concentrations. It is hypothesized that this reflects a close link between abnormalities in glucose homeostasis, amino acid catabolism, and efficiency of fuel combustion in the tricarboxylic acid (TCA) cycle. It is speculated that a mechanism for potential TCA cycle inefficiency concurrent with insulin resistance is “anaplerotic stress” emanating from reduced amino acid-derived carbon flux to TCA cycle intermediates, which if coupled to perturbation in cataplerosis would lead to net reduction in TCA cycle capacity relative to fuel delivery.
University of California, Davis
DepartmentGenome and Biomedical Sciences Facility
LaboratoryWCMC Metabolomics Core
Last NameFiehn
First NameOliver
Address1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Phone(530) 754-8258
Submit Date2016-04-11
Study CommentsG/g and g/a are polymorphisms in the promoter region of the UCP3 gene that leads to the gene being enhanced and an increased chance of obesity in those with this polymorphism.
PublicationsPlasma Metabolomic Profiles Reflective of Glucose Homeostasis in Non-Diabetic and Type 2 Diabetic Obese African-American Women
Raw Data AvailableYes
Raw Data File Type(s)peg
Analysis Type DetailGC-MS
Release Date2016-04-25
Release Version1
Oliver Fiehn Oliver Fiehn application/zip

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Sample Preparation:

Sampleprep ID:SP000411
Sampleprep Summary:1. Switch on bath to pre-cool at –20°C (±2°C validity temperature range) 2. Gently rotate or aspirate the blood samples for about 10s to obtain a homogenised sample. 3. Aliquot 30?l of plasma sample to a 1.0 mL extraction solution. The extraction solution has to be prechilled using the ThermoElectron Neslab RTE 740 cooling bath set to -20°C. 4. Vortex the sample for about 10s and shake for 5 min at 4°C using the Orbital Mixing Chilling/Heating Plate. If you are using more than one sample, keep the rest of the sample on ice (chilled at <0°C with sodium chloride). 5. Centrifuge samples for 2min at 14000 rcf using the centrifuge Eppendorf 5415 D. 6. Aliquot two 450?L portions of the supernatant. One for analysis and one for a backup sample. Store the backup aliquot in -20°C freezer. 7. Evaporate one 450?L aliquots of the sample in the Labconco Centrivap cold trap concentrator to complete dryness. 8. The dried aliquot is then re-suspended with 450 ?L 50% acetonitrile (degassed as given above). 9. Centrifuged for 2 min at 14000 rcf using the centrifuge Eppendorf 5415. 10. Remove supernatant to a new Eppendorf tube. 11. Evaporate the supernatant to dryness in the Labconco Centrivap cold trap concentrator. 12. Submit to derivatization.
Sampleprep Protocol Filename:PR_SP_SOP_blood-GCTOF-11082012.pdf