Metabolite profiles and the risk of developing diabetes

• Published in: Nature medicine Vol. 17; no. 4; pp. 448 - 453
• Main Authors: 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
• Language: English
• Published: New York Nature Publishing Group US 01.04.2011; Nature Publishing Group
• Subjects: 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; Cardiac and Cardiovascular Systems; 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; 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
• DOI: 10.1038/nm.2307

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.