title: Novel biomarkers for pre-diabetes identified by metabolomics.
abstract: 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 2.4×10(-4) to 2.1×10(-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.
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany. rui.wang-sattler@helmholtz-muenchen.de
authors.forename: Rui
authors.initials: R
authors.lastname: Wang-Sattler
authors.forename: Zhonghao
authors.initials: Z
authors.lastname: Yu
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
authors.forename: Ana C
authors.initials: AC
authors.lastname: Messias
authors.forename: Anna
authors.initials: A
authors.lastname: Floegel
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.forename: Katharina
authors.initials: K
authors.lastname: Heim
authors.forename: Monica
authors.initials: M
authors.lastname: Campillos
authors.forename: Christina
authors.initials: C
authors.lastname: Holzapfel
authors.forename: Barbara
authors.initials: B
authors.lastname: Thorand
authors.forename: Harald
authors.initials: H
authors.lastname: Grallert
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.forename: Erik
authors.initials: E
authors.lastname: Bader
authors.forename: Cornelia
authors.initials: C
authors.lastname: Huth
authors.forename: Kirstin
authors.initials: K
authors.lastname: Mittelstrass
authors.forename: Angela
authors.initials: A
authors.lastname: Döring
authors.forename: Christa
authors.initials: C
authors.lastname: Meisinger
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Cornelia
authors.initials: C
authors.lastname: Prehn
authors.forename: Werner
authors.initials: W
authors.lastname: Roemisch-Margl
authors.forename: Maren
authors.initials: M
authors.lastname: Carstensen
authors.forename: Lu
authors.initials: L
authors.lastname: Xie
authors.forename: Hisami
authors.initials: H
authors.lastname: Yamanaka-Okumura
authors.forename: Guihong
authors.initials: G
authors.lastname: Xing
authors.forename: Uta
authors.initials: U
authors.lastname: Ceglarek
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiery
authors.forename: Guido
authors.initials: G
authors.lastname: Giani
authors.forename: Heiko
authors.initials: H
authors.lastname: Lickert
authors.forename: Xu
authors.initials: X
authors.lastname: Lin
authors.forename: Yixue
authors.initials: Y
authors.lastname: Li
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Joost
authors.forename: Martin Hrabé
authors.initials: MH
authors.lastname: de Angelis
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rathmann
authors.forename: Karsten
authors.initials: K
authors.lastname: Suhre
authors.forename: Holger
authors.initials: H
authors.lastname: Prokisch
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Tobias
authors.initials: T
authors.lastname: Pischon
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005215:Fasting / Q000097:blood; D005260:Female; D005858:Germany; D005951:Glucose Tolerance Test; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D008954:Models, Biological; D016017:Odds Ratio; D011236:Prediabetic State / Q000378:metabolism*; D011446:Prospective Studies; D015203:Reproducibility of Results; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose