Summary of Study ST000168

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 PR000146. The data can be accessed directly via it's Project DOI: 10.21228/M83G6X This work is supported by NIH grant, U2C- DK119886.

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Study IDST000168
Study TitleEffect of Insulin Sensitizer Therapy on Amino Acids and Their Metabolites
Study Typedrug + time course
Study SummaryWe previously reported the overall study design for the parent study [29]. The current report primarily examines the effect of three months of insulin sensitizer therapy on plasma concentrations of BCAA, AAA, and AA metabolites in overweight/obese adults with fasting hyperglycemia, defined as either impaired fasting glucose or untreated diabetes [29]. Briefly, 25 drug naïve, Northern European American participants with fasting blood glucose concentrations of 108–180 mg/dL were randomized to receive either 45 mg of pioglitazone per day plus 1 g of metformin twice per day (n = 12) or placebo (n = 13) for 12 weeks. We chose metformin based on its proven effect on hepatic insulin sensitivity and pioglitazone based on its effect on peripheral insulin sensitivity. Current use of hypoglycemic medications excluded participants from the present study.
Institute
Mayo Clinic
DepartmentEndocrinology
LaboratorySree Nair
Last NameNair
First NameSreekumaran
EmailDasari.Surendra@mayo.edu
Submit Date2015-05-21
Num Groups2
Total Subjects27
Raw Data AvailableNo
Analysis Type DetailLC-MS
Release Date2015-06-28
Release Version1
Sreekumaran Nair Sreekumaran Nair
https://dx.doi.org/10.21228/M83G6X
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000146
Project DOI:doi: 10.21228/M83G6X
Project Title:Effect of Insulin Sensitizer Therapy on Amino Acids and Their Metabolites
Project Summary:Aims Prior studies have reported that elevated concentrations of several plasma amino acids (AA), particularly branched chain (BCAA) and aromatic AA predict the onset of type 2 diabetes. We sought to test the hypothesis that circulating BCAA, aromatic AA and related AA metabolites decline in response to the use of insulin sensitizing agents in overweight/obese adults with impaired fasting glucose or untreated diabetes. Methods We performed a secondary analysis of a randomized, double-blind, placebo, controlled study conducted in twenty five overweight/obese (BMI ~ 30 kg/m2) adults with impaired fasting glucose or untreated diabetes. Participants were randomized to three months of pioglitazone (45 mg per day) plus metformin (1000 mg twice per day, N = 12 participants) or placebo (N = 13). We measured insulin sensitivity by the euglycemic-hyperinsulinemic clamp and fasting concentrations of AA and AA metabolites using ultra-pressure liquid chromatography tandem mass spectrometry before and after the three-month intervention. Results Insulin sensitizer therapy that significantly enhanced insulin sensitivity reduced 9 out of 33 AA and AA metabolites measured compared to placebo treatment. Moreover, insulin sensitizer therapy significantly reduced three functionally clustered AA and metabolite pairs: i) phenylalanine/tyrosine, ii) citrulline/arginine, and iii) lysine/?-aminoadipic acid. Conclusions Reductions in plasma concentrations of several AA and AA metabolites in response to three months of insulin sensitizer therapy support the concept that reduced insulin sensitivity alters AA and AA metabolites.
Institute:Mayo Clinic
Department:Endocrinology
Laboratory:Sree Nair
Last Name:Nair
First Name:Sreekumaran
Email:Dasari.Surendra@mayo.edu

Subject:

Subject ID:SU000187
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Species Group:Human

Factors:

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

mb_sample_id local_sample_id Drug Pre vs. Post
SA009140ms1864-29Metformin Post
SA009141ms1874-14Metformin Post
SA009142ms1864-30Metformin Post
SA009143ms1864-31Metformin Post
SA009144ms1874-13Metformin Post
SA009145ms1864-32Metformin Post
SA009146ms1874-15Metformin Post
SA009147ms1874-16Metformin Post
SA009148ms1875-21Metformin Post
SA009149ms1875-22Metformin Post
SA009150ms1863-21Metformin Post
SA009151ms1863-22Metformin Post
SA009152ms1868-32Metformin Post
SA009153ms1863-23Metformin Post
SA009154ms1873-8Metformin Post
SA009155ms1873-7Metformin Post
SA009156ms1869-6Metformin Post
SA009157ms1869-7Metformin Post
SA009158ms1869-5Metformin Post
SA009159ms1868-29Metformin Post
SA009160ms1868-31Metformin Post
SA009161ms1868-30Metformin Post
SA009162ms1869-8Metformin Post
SA009163ms1871-21Metformin Post
SA009164ms1873-5Metformin Post
SA009165ms1873-6Metformin Post
SA009166ms1871-24Metformin Post
SA009167ms1871-23Metformin Post
SA009168ms1871-22Metformin Post
SA009169ms1875-23Metformin Post
SA009170ms1863-24Metformin Post
SA009171ms1860-5Metformin Post
SA009172ms2418-14Metformin Post
SA009173ms1860-6Metformin Post
SA009174ms1875-24Metformin Post
SA009175ms1860-8Metformin Post
SA009176ms2418-15Metformin Post
SA009177ms2418-16Metformin Post
SA009178ms2418-40Metformin Post
SA009179ms2418-39Metformin Post
SA009180ms2418-38Metformin Post
SA009181ms2418-37Metformin Post
SA009182ms2418-13Metformin Post
SA009183ms1860-7Metformin Post
SA009184ms1878-46Metformin Post
SA009185ms1878-45Metformin Post
SA009186ms1878-48Metformin Post
SA009187ms1878-47Metformin Post
SA009188ms2418-35Metformin Pre
SA009189ms2418-36Metformin Pre
SA009190ms2418-34Metformin Pre
SA009191ms1871-17Metformin Pre
SA009192ms1871-19Metformin Pre
SA009193ms1871-18Metformin Pre
SA009194ms1878-41Metformin Pre
SA009195ms1875-18Metformin Pre
SA009196ms1869-2Metformin Pre
SA009197ms1869-1Metformin Pre
SA009198ms1869-3Metformin Pre
SA009199ms1869-4Metformin Pre
SA009200ms1875-20Metformin Pre
SA009201ms2418-33Metformin Pre
SA009202ms1875-19Metformin Pre
SA009203ms1878-44Metformin Pre
SA009204ms1874-11Metformin Pre
SA009205ms1874-10Metformin Pre
SA009206ms1874-12Metformin Pre
SA009207ms2418-12Metformin Pre
SA009208ms2418-10Metformin Pre
SA009209ms2418-11Metformin Pre
SA009210ms1874-9Metformin Pre
SA009211ms1875-17Metformin Pre
SA009212ms2418-9Metformin Pre
SA009213ms1878-43Metformin Pre
SA009214ms1873-1Metformin Pre
SA009215ms1873-2Metformin Pre
SA009216ms1873-4Metformin Pre
SA009217ms1873-3Metformin Pre
SA009218ms1878-42Metformin Pre
SA009219ms1871-20Metformin Pre
SA009220ms1863-17Metformin Pre
SA009221ms1863-18Metformin Pre
SA009222ms1868-28Metformin Pre
SA009223ms1860-2Metformin Pre
SA009224ms1860-3Metformin Pre
SA009225ms1863-19Metformin Pre
SA009226ms1863-20Metformin Pre
SA009227ms1864-28Metformin Pre
SA009228ms1864-27Metformin Pre
SA009229ms1864-26Metformin Pre
SA009230ms1864-25Metformin Pre
SA009231ms1860-4Metformin Pre
SA009232ms1860-1Metformin Pre
SA009233ms1868-26Metformin Pre
SA009234ms1868-27Metformin Pre
SA009235ms1868-25Metformin Pre
SA009236ms2418-8Placebo Post
SA009237ms1861-6Placebo Post
SA009238ms1861-7Placebo Post
SA009239ms1862-16Placebo Post
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Collection:

Collection ID:CO000174
Collection Summary:we drew arterialized-venous blood samples into plasma EDTA tubes, processed, and stored them at ? 80?C until analysis.
Sample Type:Blood

Treatment:

Treatment ID:TR000194
Treatment Summary:Placebo|Metformin
Treatment Protocol Comments:We previously reported the overall study design for the parent study [29]. The current report primarily examines the effect of three months of insulin sensitizer therapy on plasma concentrations of BCAA, AAA, and AA metabolites in overweight/obese adults with fasting hyperglycemia, defined as either impaired fasting glucose or untreated diabetes [29]. Briefly, 25 drug naïve, Northern European American participants with fasting blood glucose concentrations of 108–180 mg/dL were randomized to receive either 45 mg of pioglitazone per day plus 1 g of metformin twice per day (n = 12) or placebo (n = 13) for 12 weeks. We chose metformin based on its proven effect on hepatic insulin sensitivity and pioglitazone based on its effect on peripheral insulin sensitivity. Current use of hypoglycemic medications excluded participants from the present study.|We previously reported the overall study design for the parent study [29]. The current report primarily examines the effect of three months of insulin sensitizer therapy on plasma concentrations of BCAA, AAA, and AA metabolites in overweight/obese adults with fasting hyperglycemia, defined as either impaired fasting glucose or untreated diabetes [29]. Briefly, 25 drug naïve, Northern European American participants with fasting blood glucose concentrations of 108–180 mg/dL were randomized to receive either 45 mg of pioglitazone per day plus 1 g of metformin twice per day (n = 12) or placebo (n = 13) for 12 weeks. We chose metformin based on its proven effect on hepatic insulin sensitivity and pioglitazone based on its effect on peripheral insulin sensitivity. Current use of hypoglycemic medications excluded participants from the present study.

Sample Preparation:

Sampleprep ID:SP000188
Sampleprep Summary:Storage of plasma/serum samples at ? 80?C for qualitative and quantitative metabolomics using mass spectrometry are routinely done, demonstrating little to no evidence of storage related decay including samples stored greater than 20 years [7] and [33]. The frozen samples were thawed on ice and spiked with C13-labeled internal standards and processed for analysis as previously described [32].

Combined analysis:

Analysis ID AN000262
Analysis type MS
Chromatography type
Chromatography system Waters Acquity
Column
MS Type ESI
MS instrument type Triple quadrupole
MS instrument name Thermo Quantum Ultra
Ion Mode POSITIVE
Units uM

Chromatography:

Chromatography ID:CH000185
Chromatography Summary:Amino acids in particular are relatively stable for several years, with the exception of their keto-acids (e.g., KIC), which we have not included in the present analysis. Subsequently, we separated the samples using an Acquity UPLC system, followed by mass detection using a TSQ Ultra Quantum from Thermo Finnigan running in ESI positive mode as previously described [32]. We calculated the AA and AA metabolites concentrations using 10 point standard curves as previously described [32]. We handled the pre- and post-intervention samples similarly and analyzed them in the same run. The reproducibility of the UPLC/MS/MS method in the MCRMC is excellent (average CV ~ 9.5%) [32].
Instrument Name:Waters Acquity

MS:

MS ID:MS000211
Analysis ID:AN000262
Instrument Name:Thermo Quantum Ultra
Instrument Type:Triple quadrupole
MS Type:ESI
Ion Mode:POSITIVE
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