Summary of Study ST001411

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000967. The data can be accessed directly via it's Project DOI: 10.21228/M8PX1S This work is supported by NIH grant, U2C- DK119886.

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Study IDST001411
Study TitlePlasma metabolites of lipid metabolism associate with diabetic polyneuropathy in a cohort with screen-tested type 2 diabetes: ADDITION-Denmark
Study SummaryThe global rise in type 2 diabetes (T2D) is associated with a concomitant increase in diabetic complications. Diabetic polyneuropathy (DPN), the most frequent T2D complication, is characterized by sensory peripheral nerve damage. Although managing glucose effectively slows DPN progression in type 1 diabetes patients, it has limited efficacy in neuropathic T2D patients. The metabolic syndrome (MetS) recently emerged as a major risk factor for DPN; however, the metabolites associated with MetS that correlate with DPN are unknown. We conducted a global plasma metabolomics analysis from a cohort of patients enrolled in the Anglo-Danish-Dutch study of Intensive Treatment of Diabetes in Primary Care (ADDITION), including healthy control subjects, T2D patients, and T2D DPN patients. We identified 15 total plasma metabolites that were altered in T2D DPN patients, including lipids, amino acids, and energy-related metabolites. We evaluated the correlation between these metabolites and all lipid species to identify major changes in both plasma free fatty acids and complex lipids in T2D DPN patients, and found significant alterations in the abundance of long-chain saturated fatty acids, acylcarnitines, and sphingolipids. Our study suggests that DPN in T2D is associated with novel alterations in plasma metabolites related to lipid metabolism.
Institute
University of Michigan
Last NameFeldman
First NameEva
Address5017 AATBSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200
Emailefeldman@med.umich.edu
Phone7347637274
Submit Date2020-06-22
Num Groups3
Total Subjects106
Num Males83
Num Females23
Raw Data File Type(s)wiff
Analysis Type DetailLC-MS
Release Date2021-06-15
Release Version1
Eva Feldman Eva Feldman
https://dx.doi.org/10.21228/M8PX1S
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000967
Project DOI:doi: 10.21228/M8PX1S
Project Title:Plasma metabolites of lipid metabolism associate with diabetic polyneuropathy in a cohort with screen-tested type 2 diabetes: ADDITION-Denmark
Project Summary:The global rise in type 2 diabetes (T2D) is associated with a concomitant increase in diabetic complications. Diabetic polyneuropathy (DPN), the most frequent T2D complication, is characterized by sensory peripheral nerve damage. Although managing glucose effectively slows DPN progression in type 1 diabetes patients, it has limited efficacy in neuropathic T2D patients. The metabolic syndrome (MetS) recently emerged as a major risk factor for DPN; however, the metabolites associated with MetS that correlate with DPN are unknown. We conducted a global plasma metabolomics analysis from a cohort of patients enrolled in the Anglo-Danish-Dutch study of Intensive Treatment of Diabetes in Primary Care (ADDITION), including healthy control subjects, T2D patients, and T2D DPN patients. We identified 15 total plasma metabolites that were altered in T2D DPN patients, including lipids, amino acids, and energy-related metabolites. We evaluated the correlation between these metabolites and all lipid species to identify major changes in both plasma free fatty acids and complex lipids in T2D DPN patients, and found significant alterations in the abundance of long-chain saturated fatty acids, acylcarnitines, and sphingolipids. Our study suggests that DPN in T2D is associated with novel alterations in plasma metabolites related to lipid metabolism.
Institute:University of Michigan
Department:Neurology
Laboratory:Feldman's lab
Last Name:Feldman
First Name:Eva
Address:5017 AATBSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200
Email:efeldman@med.umich.edu
Phone:7347637274
Funding Source:Support for this research was provided by the Novo Nordisk Foundation through a Novo Nordisk Foundation Challenge Programme grant (NNF14OC0011633), the National Institutes of Health (1R24082841, 1R21NS102924, and 1DP3DK094292), the National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) (1F32DK112642 and 1K99DK119366), the American Diabetes Association (7-12-BS-045), the NeuroNetwork for Emerging Therapies, and the A. Alfred Taubman Medical Research Institute.

Subject:

Subject ID:SU001485
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Group
SA115723MICH-01469Diabetic Neuropathy
SA115724MICH-01468Diabetic Neuropathy
SA115725MICH-01466Diabetic Neuropathy
SA115726MICH-01470Diabetic Neuropathy
SA115727MICH-01419Diabetic Neuropathy
SA115728MICH-01481Diabetic Neuropathy
SA115729MICH-01473Diabetic Neuropathy
SA115730MICH-01465Diabetic Neuropathy
SA115731MICH-01464Diabetic Neuropathy
SA115732MICH-01454Diabetic Neuropathy
SA115733MICH-01453Diabetic Neuropathy
SA115734MICH-01455Diabetic Neuropathy
SA115735MICH-01459Diabetic Neuropathy
SA115736MICH-01463Diabetic Neuropathy
SA115737MICH-01462Diabetic Neuropathy
SA115738MICH-01482Diabetic Neuropathy
SA115739MICH-01483Diabetic Neuropathy
SA115740MICH-01510Diabetic Neuropathy
SA115741MICH-01507Diabetic Neuropathy
SA115742MICH-01511Diabetic Neuropathy
SA115743MICH-01512Diabetic Neuropathy
SA115744MICH-01515Diabetic Neuropathy
SA115745MICH-01514Diabetic Neuropathy
SA115746MICH-01504Diabetic Neuropathy
SA115747MICH-01502Diabetic Neuropathy
SA115748MICH-01490Diabetic Neuropathy
SA115749MICH-01485Diabetic Neuropathy
SA115750MICH-01491Diabetic Neuropathy
SA115751MICH-01492Diabetic Neuropathy
SA115752MICH-01496Diabetic Neuropathy
SA115753MICH-01495Diabetic Neuropathy
SA115754MICH-01452Diabetic Neuropathy
SA115755MICH-01472Diabetic Neuropathy
SA115756MICH-01430Diabetic Neuropathy
SA115757MICH-01426Diabetic Neuropathy
SA115758MICH-01444Diabetic Neuropathy
SA115759MICH-01429Diabetic Neuropathy
SA115760MICH-01441Diabetic Neuropathy
SA115761MICH-01428Diabetic Neuropathy
SA115762MICH-01439Diabetic Neuropathy
SA115763MICH-01447Diabetic Neuropathy
SA115764MICH-01446Diabetic Neuropathy
SA115765MICH-01436Diabetic Neuropathy
SA115766MICH-01422Diabetic Neuropathy
SA115767MICH-01432Diabetic Neuropathy
SA115768MICH-01431Diabetic Neuropathy
SA115769MICH-01434Diabetic Neuropathy
SA115770MICH-01425Diabetic Neuropathy
SA115771MICH-01433Diabetic non neuropathy
SA115772MICH-01499Diabetic non neuropathy
SA115773MICH-01500Diabetic non neuropathy
SA115774MICH-01497Diabetic non neuropathy
SA115775MICH-01494Diabetic non neuropathy
SA115776MICH-01493Diabetic non neuropathy
SA115777MICH-01498Diabetic non neuropathy
SA115778MICH-01427Diabetic non neuropathy
SA115779MICH-01423Diabetic non neuropathy
SA115780MICH-01424Diabetic non neuropathy
SA115781MICH-01513Diabetic non neuropathy
SA115782MICH-01421Diabetic non neuropathy
SA115783MICH-01420Diabetic non neuropathy
SA115784MICH-01509Diabetic non neuropathy
SA115785MICH-01508Diabetic non neuropathy
SA115786MICH-01503Diabetic non neuropathy
SA115787MICH-01451Diabetic non neuropathy
SA115788MICH-01505Diabetic non neuropathy
SA115789MICH-01506Diabetic non neuropathy
SA115790MICH-01501Diabetic non neuropathy
SA115791MICH-01489Diabetic non neuropathy
SA115792MICH-01445Diabetic non neuropathy
SA115793MICH-01461Diabetic non neuropathy
SA115794MICH-01488Diabetic non neuropathy
SA115795MICH-01467Diabetic non neuropathy
SA115796MICH-01440Diabetic non neuropathy
SA115797MICH-01442Diabetic non neuropathy
SA115798MICH-01460Diabetic non neuropathy
SA115799MICH-01448Diabetic non neuropathy
SA115800MICH-01449Diabetic non neuropathy
SA115801MICH-01450Diabetic non neuropathy
SA115802MICH-01456Diabetic non neuropathy
SA115803MICH-01457Diabetic non neuropathy
SA115804MICH-01458Diabetic non neuropathy
SA115805MICH-01471Diabetic non neuropathy
SA115806MICH-01443Diabetic non neuropathy
SA115807MICH-01435Diabetic non neuropathy
SA115808MICH-01437Diabetic non neuropathy
SA115809MICH-01438Diabetic non neuropathy
SA115810MICH-01486Diabetic non neuropathy
SA115811MICH-01487Diabetic non neuropathy
SA115812MICH-01480Diabetic non neuropathy
SA115813MICH-01484Diabetic non neuropathy
SA115814MICH-01474Diabetic non neuropathy
SA115815MICH-01479Diabetic non neuropathy
SA115816MICH-01476Diabetic non neuropathy
SA115817MICH-01475Diabetic non neuropathy
SA115818MICH-01478Diabetic non neuropathy
SA115819MICH-01477Diabetic non neuropathy
SA115820MICH-01523Normal
SA115821MICH-01522Normal
SA115822MICH-01524Normal
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Collection:

Collection ID:CO001480
Collection Summary:At the mean 13 year follow up after T2D diagnosis, blood samples were collected from patients the same day as anthropometrics and DPN assessment. Plasma was collected in purple EDTA tubes with 10 mL of buffy coat, inverted 10 times, incubated for 30-90 minutes at room temperature, and centrifuged at 3000 rpm for 10 minutes. The plasma supernatant was collected by aspirating plasma to approximately 5 mm above the buffy coat and plasma samples were stored in 0.5 mL aliquots at -80C prior to metabolomics analysis.
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR001500
Treatment Summary:NA

Sample Preparation:

Sampleprep ID:SP001493
Sampleprep Summary:Samples were prepared using the automated MicroLab STAR® system from Hamilton Company. Several recovery standards were added prior to the first step in the extraction process for QC purposes. To remove protein, dissociate small molecules bound to protein or trapped in the precipitated protein matrix, and to recover chemically diverse metabolites, proteins were precipitated with methanol under vigorous shaking for 2 min (Glen Mills GenoGrinder 2000) followed by centrifugation. The resulting extract was divided into five fractions: two for analysis by two separate reverse phase (RP)/UPLC-MS/MS methods with positive ion mode electrospray ionization (ESI), one for analysis by RP/UPLC-MS/MS with negative ion mode ESI, one for analysis by HILIC/UPLC-MS/MS with negative ion mode ESI, and one sample was reserved for backup. Samples were placed briefly on a TurboVap® (Zymark) to remove the organic solvent. The sample extracts were stored overnight under nitrogen before preparation for analysis.

Combined analysis:

Analysis ID AN002361
Analysis type MS
Chromatography type HILIC
Chromatography system Waters Acquity
Column Waters Acquity CSH C18 (100 x 2.1mm, 1.7um)
MS Type ESI
MS instrument type UPLC-MS
MS instrument name Waters Acquity
Ion Mode POSITIVE
Units peak area

Chromatography:

Chromatography ID:CH001731
Instrument Name:Waters Acquity
Column Name:Waters Acquity CSH C18 (100 x 2.1mm, 1.7um)
Chromatography Type:HILIC

MS:

MS ID:MS002203
Analysis ID:AN002361
Instrument Name:Waters Acquity
Instrument Type:UPLC-MS
MS Type:ESI
MS Comments:The informatics system consisted of four major components, the Laboratory Information Management System (LIMS), the data extraction and peak-identification software, data processing tools for QC and compound identification, and a collection of information interpretation and visualization tools for use by data analysts. The hardware and software foundations for these informatics components were the LAN backbone, and a database server running Oracle 10.2.0.1 Enterprise Edition.
Ion Mode:POSITIVE
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