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

被引：814

作者：

Floegel, Anna ^{[1
]}

Stefan, Norbert ^{[2
,3
,4
,5
,6
]}

Yu, Zhonghao ^{[7
]}

Muehlenbruch, Kristin ^{[8
]}

Drogan, Dagmar ^{[1
]}

Joost, Hans-Georg ^{[9
]}

Fritsche, Andreas ^{[2
,3
,4
,5
,6
]}

Haering, Hans-Ulrich ^{[2
,3
,4
,5
,6
]}

de Angelis, Martin Hrabe ^{[10
]}

Peters, Annette ^{[11
]}

Roden, Michael ^{[12
,13
]}

Prehn, Cornelia ^{[10
]}

Wang-Sattler, Rui ^{[7
]}

Illig, Thomas ^{[7
,14
]}

Schulze, Matthias B. ^{[8
]}

Adamski, Jerzy ^{[10
]}

Boeing, Heiner ^{[1
]}

Pischon, Tobias ^{[1
,15
]}

机构：

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

[2] Univ Tubingen, Dept Internal Med 4, Div Endocrinol, Tubingen, Germany

[3] Univ Tubingen, Dept Internal Med 4, Div Diabetol, Tubingen, Germany

[4] Univ Tubingen, Dept Internal Med 4, Div Nephrol, Tubingen, Germany

[5] Univ Tubingen, Dept Internal Med 4, Div Vasc Dis, Tubingen, Germany

[6] Univ Tubingen, Dept Internal Med 4, Div Clin Chem, Tubingen, Germany

[7] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany

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

[9] German Inst Human Nutr Potsdam Rehbrucke, Dept Pharmacol, Nuthetal, Germany

[10] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Expt Genet, Neuherberg, Germany

[11] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany

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

[13] Univ Clin, Dept Metab Dis, Dusseldorf, Germany

[14] Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany

[15] Max Delbruck Ctr Mol Med MDC Berlin Buch, Mol Epidemiol Grp, Berlin, Germany

来源：

DIABETES | 2013年 / 62卷 / 02期

关键词：

FETUIN-A LEVELS; EPIC-GERMANY; OBESITY; DIETARY; CANCER; ADIPONECTIN; POPULATION; OXIDATION; PROFILES; ENZYMES;

D O I：

10.2337/db12-0495

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 Tubingen 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. Diabetes 62:639-648, 2013

引用

页码：639 / 648

页数：10

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