Metabolite profiles and the risk of developing diabetes

Amino acid profiles could aid in diabetes risk assessment, as a five-amino-acid signature had highly significant associations with the development of future diabetes in two large, independent cohorts. Emerging technologies allow the high-throughput profiling of metabolic status from a blood specimen...

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Veröffentlicht in:Nature medicine Jg. 17; H. 4; S. 448 - 453
Hauptverfasser: Wang, Thomas J, Larson, Martin G, Vasan, Ramachandran S, Cheng, Susan, Rhee, Eugene P, McCabe, Elizabeth, Lewis, Gregory D, Fox, Caroline S, Jacques, Paul F, Fernandez, Céline, O'Donnell, Christopher J, Carr, Stephen A, Mootha, Vamsi K, Florez, Jose C, Souza, Amanda, Melander, Olle, Clish, Clary B, Gerszten, Robert E
Format: Journal Article
Sprache:Englisch
Veröffentlicht: New York Nature Publishing Group US 01.04.2011
Nature Publishing Group
Schlagworte:
631/1647/320
692/499
692/699/2743/137/773
Aged
Amines
Amino acids
Amino Acids, Aromatic - blood
Amino Acids, Branched-Chain - blood
Biomarkers - blood
Biomedical and Life Sciences
Biomedicine
Blood
Blood sugar
Body mass index
Cancer Research
Cardiology and Cardiovascular Disease
Case-Control Studies
Causality
Clinical Medicine
Cohort Studies
Diabetes
Diabetes Mellitus - blood
Diabetes Mellitus - etiology
Female
Health aspects
Health risks
Humans
Infectious Diseases
Kardiologi och kardiovaskulära sjukdomar
Klinisk medicin
Liquid chromatography
Logistic Models
Longitudinal Studies
Male
Mass spectrometry
Medical and Health Sciences
Medicin och hälsovetenskap
Metabolic Diseases
Metabolism
Metabolites
Metabolome
Middle Aged
Molecular Medicine
Neurosciences
Pathogenesis
Physiological aspects
Predictive Value of Tests
Prospective Studies
Risk assessment
Risk Factors
Tandem Mass Spectrometry
Sweden
ISSN:1078-8956, 1546-170X, 1546-170X
Online-Zugang:Volltext
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Zusammenfassung:Amino acid profiles could aid in diabetes risk assessment, as a five-amino-acid signature had highly significant associations with the development of future diabetes in two large, independent cohorts. 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.
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ISSN:1078-8956
1546-170X
1546-170X
DOI:10.1038/nm.2307