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Identification of Serum Metabolites Associated With Risk of Type 2 Diabetes Using a Targeted Metabolomic Approach

Metabolomic discovery of biomarkers of type 2 diabetes (T2D) risk may reveal etiological pathways and help to identify individuals at risk for disease. We prospectively investigated the association between serum metabolites measured by targeted metabolomics and risk of T2D in the European Prospectiv...

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Autores principales: Floegel, Anna, Stefan, Norbert, Yu, Zhonghao, Mühlenbruch, Kristin, Drogan, Dagmar, Joost, Hans-Georg, Fritsche, Andreas, Häring, Hans-Ulrich, Hrabě de Angelis, Martin, Peters, Annette, Roden, Michael, Prehn, Cornelia, Wang-Sattler, Rui, Illig, Thomas, Schulze, Matthias B., Adamski, Jerzy, Boeing, Heiner, Pischon, Tobias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554384/
https://www.ncbi.nlm.nih.gov/pubmed/23043162
http://dx.doi.org/10.2337/db12-0495
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author Floegel, Anna
Stefan, Norbert
Yu, Zhonghao
Mühlenbruch, Kristin
Drogan, Dagmar
Joost, Hans-Georg
Fritsche, Andreas
Häring, Hans-Ulrich
Hrabě de Angelis, Martin
Peters, Annette
Roden, Michael
Prehn, Cornelia
Wang-Sattler, Rui
Illig, Thomas
Schulze, Matthias B.
Adamski, Jerzy
Boeing, Heiner
Pischon, Tobias
author_facet Floegel, Anna
Stefan, Norbert
Yu, Zhonghao
Mühlenbruch, Kristin
Drogan, Dagmar
Joost, Hans-Georg
Fritsche, Andreas
Häring, Hans-Ulrich
Hrabě de Angelis, Martin
Peters, Annette
Roden, Michael
Prehn, Cornelia
Wang-Sattler, Rui
Illig, Thomas
Schulze, Matthias B.
Adamski, Jerzy
Boeing, Heiner
Pischon, Tobias
author_sort Floegel, Anna
collection PubMed
description Metabolomic discovery of biomarkers of type 2 diabetes (T2D) risk may reveal etiological pathways and help to identify individuals at risk for disease. We prospectively investigated the association between serum metabolites measured by targeted metabolomics and risk of T2D in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam (27,548 adults) among all incident cases of T2D (n = 800, mean follow-up 7 years) and a randomly drawn subcohort (n = 2,282). Flow injection analysis tandem mass spectrometry was used to quantify 163 metabolites, including acylcarnitines, amino acids, hexose, and phospholipids, in baseline serum samples. Serum hexose; phenylalanine; and diacyl-phosphatidylcholines C32:1, C36:1, C38:3, and C40:5 were independently associated with increased risk of T2D and serum glycine; sphingomyelin C16:1; acyl-alkyl-phosphatidylcholines C34:3, C40:6, C42:5, C44:4, and C44:5; and lysophosphatidylcholine C18:2 with decreased risk. Variance of the metabolites was largely explained by two metabolite factors with opposing risk associations (factor 1 relative risk in extreme quintiles 0.31 [95% CI 0.21–0.44], factor 2 3.82 [2.64–5.52]). The metabolites significantly improved T2D prediction compared with established risk factors. They were further linked to insulin sensitivity and secretion in the Tübingen Family study and were partly replicated in the independent KORA (Cooperative Health Research in the Region of Augsburg) cohort. The data indicate that metabolic alterations, including sugar metabolites, amino acids, and choline-containing phospholipids, are associated early on with a higher risk of T2D.
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spelling pubmed-35543842014-02-01 Identification of Serum Metabolites Associated With Risk of Type 2 Diabetes Using a Targeted Metabolomic Approach Floegel, Anna Stefan, Norbert Yu, Zhonghao Mühlenbruch, Kristin Drogan, Dagmar Joost, Hans-Georg Fritsche, Andreas Häring, Hans-Ulrich Hrabě de Angelis, Martin Peters, Annette Roden, Michael Prehn, Cornelia Wang-Sattler, Rui Illig, Thomas Schulze, Matthias B. Adamski, Jerzy Boeing, Heiner Pischon, Tobias Diabetes Genetics/Genomes/Proteomics/Metabolomics Metabolomic discovery of biomarkers of type 2 diabetes (T2D) risk may reveal etiological pathways and help to identify individuals at risk for disease. We prospectively investigated the association between serum metabolites measured by targeted metabolomics and risk of T2D in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam (27,548 adults) among all incident cases of T2D (n = 800, mean follow-up 7 years) and a randomly drawn subcohort (n = 2,282). Flow injection analysis tandem mass spectrometry was used to quantify 163 metabolites, including acylcarnitines, amino acids, hexose, and phospholipids, in baseline serum samples. Serum hexose; phenylalanine; and diacyl-phosphatidylcholines C32:1, C36:1, C38:3, and C40:5 were independently associated with increased risk of T2D and serum glycine; sphingomyelin C16:1; acyl-alkyl-phosphatidylcholines C34:3, C40:6, C42:5, C44:4, and C44:5; and lysophosphatidylcholine C18:2 with decreased risk. Variance of the metabolites was largely explained by two metabolite factors with opposing risk associations (factor 1 relative risk in extreme quintiles 0.31 [95% CI 0.21–0.44], factor 2 3.82 [2.64–5.52]). The metabolites significantly improved T2D prediction compared with established risk factors. They were further linked to insulin sensitivity and secretion in the Tübingen Family study and were partly replicated in the independent KORA (Cooperative Health Research in the Region of Augsburg) cohort. The data indicate that metabolic alterations, including sugar metabolites, amino acids, and choline-containing phospholipids, are associated early on with a higher risk of T2D. American Diabetes Association 2013-02 2013-01-17 /pmc/articles/PMC3554384/ /pubmed/23043162 http://dx.doi.org/10.2337/db12-0495 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Genetics/Genomes/Proteomics/Metabolomics
Floegel, Anna
Stefan, Norbert
Yu, Zhonghao
Mühlenbruch, Kristin
Drogan, Dagmar
Joost, Hans-Georg
Fritsche, Andreas
Häring, Hans-Ulrich
Hrabě de Angelis, Martin
Peters, Annette
Roden, Michael
Prehn, Cornelia
Wang-Sattler, Rui
Illig, Thomas
Schulze, Matthias B.
Adamski, Jerzy
Boeing, Heiner
Pischon, Tobias
Identification of Serum Metabolites Associated With Risk of Type 2 Diabetes Using a Targeted Metabolomic Approach
title Identification of Serum Metabolites Associated With Risk of Type 2 Diabetes Using a Targeted Metabolomic Approach
title_full Identification of Serum Metabolites Associated With Risk of Type 2 Diabetes Using a Targeted Metabolomic Approach
title_fullStr Identification of Serum Metabolites Associated With Risk of Type 2 Diabetes Using a Targeted Metabolomic Approach
title_full_unstemmed Identification of Serum Metabolites Associated With Risk of Type 2 Diabetes Using a Targeted Metabolomic Approach
title_short Identification of Serum Metabolites Associated With Risk of Type 2 Diabetes Using a Targeted Metabolomic Approach
title_sort identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach
topic Genetics/Genomes/Proteomics/Metabolomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554384/
https://www.ncbi.nlm.nih.gov/pubmed/23043162
http://dx.doi.org/10.2337/db12-0495
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