Novel biomarkers for pre-diabetes identified by metabolomics

被引：594

作者：

Wang-Sattler, Rui ^{[1
]}

Yu, Zhonghao ^{[1
]}

Herder, Christian ^{[2
]}

Messias, Ana C. ^{[3
]}

Floegel, Anna ^{[4
]}

He, Ying ^{[5
,6
]}

Heim, Katharina ^{[7
]}

Campillos, Monica ^{[8
]}

Holzapfel, Christina ^{[1
,9
]}

Thorand, Barbara ^{[10
]}

Grallert, Harald ^{[1
]}

Xu, Tao ^{[1
]}

Bader, Erik ^{[1
]}

Huth, Cornelia ^{[10
]}

Mittelstrass, Kirstin ^{[1
]}

Doering, Angela ^{[11
]}

Meisinger, Christa ^{[10
]}

Gieger, Christian ^{[12
]}

Prehn, Cornelia ^{[13
]}

Roemisch-Margl, Werner ^{[8
]}

Carstensen, Maren ^{[2
]}

Xie, Lu ^{[5
]}

Yamanaka-Okumura, Hisami ^{[14
]}

Xing, Guihong ^{[15
]}

Ceglarek, Uta ^{[16
]}

Thiery, Joachim ^{[16
]}

Giani, Guido ^{[17
]}

Lickert, Heiko ^{[18
]}

Lin, Xu ^{[19
]}

Li, Yixue ^{[5
,6
]}

Boeing, Heiner ^{[4
]}

Joost, Hans-Georg ^{[4
]}

de Angelis, Martin Hrabe ^{[13
,20
]}

Rathmann, Wolfgang ^{[17
]}

Suhre, Karsten ^{[8
,21
,22
]}

Prokisch, Holger ^{[7
]}

Peters, Annette ^{[10
]}

Meitinger, Thomas ^{[5
,6
,7
,23
]}

Roden, Michael ^{[2
]}

Wichmann, H-Erich ^{[11
,24
]}

Pischon, Tobias ^{[4
,25
]}

Adamski, Jerzy ^{[13
,20
]}

Illig, Thomas ^{[1
,26
]}

机构：

[1] Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany

[2] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, D-40225 Dusseldorf, Germany

[3] Helmholtz Zentrum Munchen, Inst Biol Struct, Neuherberg, Germany

[4] German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, Nuthetal, Germany

[5] Shanghai Ctr Bioinformat Technol, Shanghai, Peoples R China

[6] Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Syst Biol, Bioinformat Ctr, Shanghai, Peoples R China

[7] Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany

[8] Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol, Neuherberg, Germany

[9] Tech Univ Munich, Klinikum Rechts Isar, Univ Hosp, Else Kroener Fresenius Ctr Nutr Med, D-8000 Munich, Germany

[10] Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany

[11] Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany

[12] Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany

[13] Helmholtz Zentrum Munchen, Inst Expt Genet, Genome Anal Ctr, Neuherberg, Germany

[14] Univ Tokushima, Grad Sch, Dept Clin Nutr, Inst Hlth Biosci, Tokushima 770, Japan

[15] Benxi Cent Hosp, Benxi Diabet Clin, Benxi, Peoples R China

[16] Univ Hosp Leipzig, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany

[17] Univ Dusseldorf, German Diabet Ctr, Inst Biometr & Epidemiol, Leibniz Ctr Diabet Res, D-40225 Dusseldorf, Germany

[18] Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, Neuherberg, Germany

[19] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai, Peoples R China

[20] Tech Univ Munich, Chair Expt Genet, Munich, Germany

[21] Univ Munich, Fac Biol, Planegg Martinsried, Germany

[22] WCMC Q, Dept Physiol & Biophys, Doha, Qatar

[23] Univ Hosp Dusseldorf, Dept Metab Dis, Dusseldorf, Germany

[24] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany

[25] Max Delbrueck Ctr Mol Med MDC, Mol Epidemiol Grp, Berlin, Germany

[26] Hannover Med Sch, Hannover Unified Biobank, D-3000 Hannover, Germany

来源：

MOLECULAR SYSTEMS BIOLOGY | 2012年 / 8卷

关键词：

early diagnostic biomarkers; IGT; metabolomics; prediction; T2D; TYPE-2; DIABETES-MELLITUS; GLUCOSE-TOLERANCE TEST; FATTY-ACID OXIDATION; INSULIN SENSITIVITY; EPIC-GERMANY; RISK; POPULATION; KORA; MUSCLE; RESISTANCE;

D O I：

10.1038/msb.2012.43

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Type 2 diabetes (T2D) can be prevented in pre-diabetic individuals with impaired glucose tolerance (IGT). Here, we have used a metabolomics approach to identify candidate biomarkers of pre-diabetes. We quantified 140 metabolites for 4297 fasting serum samples in the population-based Cooperative Health Research in the Region of Augsburg (KORA) cohort. Our study revealed significant metabolic variation in pre-diabetic individuals that are distinct from known diabetes risk indicators, such as glycosylated hemoglobin levels, fasting glucose and insulin. We identified three metabolites (glycine, lysophosphatidylcholine (LPC) (18:2) and acetylcarnitine) that had significantly altered levels in IGT individuals as compared to those with normal glucose tolerance, with P-values ranging from 2.4 x 10(-4) to 2.1 x 10(-13). Lower levels of glycine and LPC were found to be predictors not only for IGT but also for T2D, and were independently confirmed in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. Using metabolite-protein network analysis, we identified seven T2D-related genes that are associated with these three IGT-specific metabolites by multiple interactions with four enzymes. The expression levels of these enzymes correlate with changes in the metabolite concentrations linked to diabetes. Our results may help developing novel strategies to prevent T2D. Molecular Systems Biology 8: 615; published online 25 September 2012; doi:10.1038/msb.2012.43

引用

页数：11

共 50 条

[1]

Plasma Acylcarnitine Profiles Suggest Incomplete Long-Chain Fatty Acid β-Oxidation and Altered Tricarboxylic Acid Cycle Activity in Type 2 Diabetic African-American Women [J].

Adams, Sean H. ;

Hoppel, Charles L. ;

Lok, Kerry H. ;

Zhao, Ling ;

Wong, Scott W. ;

Minkler, Paul E. ;

Hwang, Daniel H. ;

Newman, John W. ;

Garvey, W. Timothy .

JOURNAL OF NUTRITION, 2009, 139 (06) :1073-1081

[2]

Questionnaire-based self-reported nutrition habits associate with serum metabolism as revealed by quantitative targeted metabolomics [J].

Altmaier, Elisabeth ;

Kastenmueller, Gabi ;

Roemisch-Margl, Werner ;

Thorand, Barbara ;

Weinberger, Klaus M. ;

Illig, Thomas ;

Adamski, Jerzy ;

Doering, Angela ;

Suhre, Karsten .

EUROPEAN JOURNAL OF EPIDEMIOLOGY, 2011, 26 (02) :145-156

[3]

[Anonymous], 2010, Diabetes Care, V33 Suppl 1, pS4, DOI 10.2337/dc10-S004

[4]

[Anonymous], DEF DIAGN CLASS DIAB

[5]

[Anonymous], METABOLOMICS

[6]

Follow-up procedures in EPIC-Germany - Data quality aspects [J].

Bergmann, MM ;

Bussas, U ;

Boeing, H .

ANNALS OF NUTRITION AND METABOLISM, 1999, 43 (04) :225-234

[7]

2 DIFFERENT GENES ENCODE DELTA-AMINOLEVULINATE SYNTHASE IN HUMANS - NUCLEOTIDE-SEQUENCES OF CDNAS FOR THE HOUSEKEEPING AND ERYTHROID GENES [J].

BISHOP, DF .

NUCLEIC ACIDS RESEARCH, 1990, 18 (23) :7187-7188

[8]

EPIC-Germany - A source for studies into diet and risk of chronic diseases [J].

Boeing, H ;

Wahrendorf, J ;

Becker, N .

ANNALS OF NUTRITION AND METABOLISM, 1999, 43 (04) :195-204

[9]

A comparison of normalization methods for high density oligonucleotide array data based on variance and bias [J].

Bolstad, BM ;

Irizarry, RA ;

Åstrand, M ;

Speed, TP .

BIOINFORMATICS, 2003, 19 (02) :185-193

[10]

Random forests [J].

Breiman, L .

MACHINE LEARNING, 2001, 45 (01) :5-32

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