Metabolite profiles and the risk of developing diabetes

被引：2395

作者：

Wang, Thomas J. ^{[1
,2
,3
,4
]}

Larson, Martin G. ^{[3
,4
,5
]}

Vasan, Ramachandran S. ^{[3
,4
,6
]}

Cheng, Susan ^{[2
,3
,4
,7
]}

Rhee, Eugene P. ^{[1
,8
,9
]}

McCabe, Elizabeth ^{[2
,3
,4
]}

Lewis, Gregory D. ^{[1
,2
,9
]}

Fox, Caroline S. ^{[3
,4
,10
,11
]}

Jacques, Paul F. ^{[12
]}

Fernandez, Celine ^{[13
]}

O'Donnell, Christopher J. ^{[2
,3
,4
,9
]}

Carr, Stephen A. ^{[9
]}

Mootha, Vamsi K. ^{[9
,14
,15
]}

Florez, Jose C. ^{[9
,14
]}

Souza, Amanda ^{[9
]}

Melander, Olle ^{[16
]}

Clish, Clary B. ^{[9
]}

Gerszten, Robert E. ^{[1
,2
,9
]}

机构：

[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA

[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA

[3] Boston Univ, Sch Med, Framingham, MA USA

[4] NHLBI, Framingham Heart Study, Framingham, MA USA

[5] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA

[6] Boston Univ, Sch Med, Boston Med Ctr, Cardiol Sect, Boston, MA 02118 USA

[7] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiol, Boston, MA USA

[8] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Renal, Boston, MA USA

[9] Broad Inst MIT & Harvard, Cambridge, MA USA

[10] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol, Boston, MA USA

[11] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA

[12] Tufts Univ, Jean Mayer US Dept, Agr Human Nutr Res Ctr, Boston, MA 02111 USA

[13] Lund Univ, Dept Expt Med Sci, Malmo, Sweden

[14] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Diabet Unit, Boston, MA USA

[15] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA

[16] Lund Univ, Dept Clin Sci, Malmo, Sweden

来源：

NATURE MEDICINE | 2011年 / 17卷 / 04期

基金：

美国国家卫生研究院;

关键词：

IMPAIRED GLUCOSE-TOLERANCE; AMINO-ACID; INSULIN-SECRETION; PROTEIN; PREDICTION; RESISTANCE; MIXTURES; MUSCLE; OBESE; DIET;

D O I：

10.1038/nm.2307

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Emerging technologies allow the high-throughput profiling of metabolic status from a blood specimen (metabolomics). We investigated whether metabolite profiles could predict the development of diabetes. Among 2,422 normoglycemic individuals followed for 12 years, 201 developed diabetes. Amino acids, amines and other polar metabolites were profiled in baseline specimens by liquid chromatography-tandem mass spectrometry (LC-MS). Cases and controls were matched for age, body mass index and fasting glucose. Five branched-chain and aromatic amino acids had highly significant associations with future diabetes: isoleucine, leucine, valine, tyrosine and phenylalanine. A combination of three amino acids predicted future diabetes (with a more than fivefold higher risk for individuals in top quartile). The results were replicated in an independent, prospective cohort. These findings underscore the potential key role of amino acid metabolism early in the pathogenesis of diabetes and suggest that amino acid profiles could aid in diabetes risk assessment.

引用

页码：448 / U83

页数：7

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