Metabolite profiles and the risk of developing diabetes

Thomas J. Wang; Martin G. Larson; Ramachandran S. Vasan; Susan Cheng; Eugene P. Rhee; Elizabeth McCabe; Gregory D. Lewis; Caroline S. Fox; Paul F. Jacques; Celine Fernandez; Christopher J. O'Donnell; Stephen A. Carr; Vamsi K. Mootha; Jose C. Florez; Amanda Souza; Olle Melander; Clary B. Clish; Robert E. Gerszten

doi:10.1038/nm.2307

Metabolite profiles and the risk of developing diabetes

Thomas J. Wang, Martin G. Larson, Ramachandran S. Vasan, Susan Cheng, Eugene P. Rhee, Elizabeth McCabe, Gregory D. Lewis, Caroline S. Fox, Paul F. Jacques, Celine Fernandez, Christopher J. O'Donnell, Stephen A. Carr, Vamsi K. Mootha, Jose C. Florez, Amanda Souza, Olle Melander, Clary B. Clish, Robert E. Gerszten

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	448-U83
Journal	Nature Medicine
Volume	17
Issue number	4
DOIs	https://doi.org/10.1038/nm.2307
Publication status	Published - 2011

Subject classification (UKÄ)

Cardiology and Cardiovascular Disease

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nm.2307

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Wang, T. J., Larson, M. G., Vasan, R. S., Cheng, S., Rhee, E. P., McCabe, E., Lewis, G. D., Fox, C. S., Jacques, P. F., Fernandez, C., O'Donnell, C. J., Carr, S. A., Mootha, V. K., Florez, J. C., Souza, A., Melander, O., Clish, C. B., & Gerszten, R. E. (2011). Metabolite profiles and the risk of developing diabetes. Nature Medicine, 17(4), 448-U83. https://doi.org/10.1038/nm.2307

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title = "Metabolite profiles and the risk of developing diabetes",

abstract = "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.",

author = "Wang, {Thomas J.} and Larson, {Martin G.} and Vasan, {Ramachandran S.} and Susan Cheng and Rhee, {Eugene P.} and Elizabeth McCabe and Lewis, {Gregory D.} and Fox, {Caroline S.} and Jacques, {Paul F.} and Celine Fernandez and O'Donnell, {Christopher J.} and Carr, {Stephen A.} and Mootha, {Vamsi K.} and Florez, {Jose C.} and Amanda Souza and Olle Melander and Clish, {Clary B.} and Gerszten, {Robert E.}",

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doi = "10.1038/nm.2307",

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journal = "Nature Medicine",

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T1 - Metabolite profiles and the risk of developing diabetes

AU - Wang, Thomas J.

AU - Larson, Martin G.

AU - Vasan, Ramachandran S.

AU - Cheng, Susan

AU - Rhee, Eugene P.

AU - McCabe, Elizabeth

AU - Lewis, Gregory D.

AU - Fox, Caroline S.

AU - Jacques, Paul F.

AU - Fernandez, Celine

AU - O'Donnell, Christopher J.

AU - Carr, Stephen A.

AU - Mootha, Vamsi K.

AU - Florez, Jose C.

AU - Souza, Amanda

AU - Melander, Olle

AU - Clish, Clary B.

AU - Gerszten, Robert E.

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

U2 - 10.1038/nm.2307

DO - 10.1038/nm.2307

M3 - Article

C2 - 21423183

SN - 1546-170X

VL - 17

SP - 448-U83

JO - Nature Medicine

JF - Nature Medicine

IS - 4

ER -

Metabolite profiles and the risk of developing diabetes

Abstract

Subject classification (UKÄ)

UN SDGs

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