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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| Vydáno v: | Nature medicine Ročník 17; číslo 4; s. 448 - 453 |
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| Hlavní autoři: | , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
New York
Nature Publishing Group US
01.04.2011
Nature Publishing Group |
| Témata: | |
| ISSN: | 1078-8956, 1546-170X, 1546-170X |
| On-line přístup: | Získat plný text |
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| Abstract | 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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| AbstractList | 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. 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. 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. [PUBLICATION 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 using liquid chromatography-tandem mass spectrometry. 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 (>5-fold higher risk for individuals in top quartile). The results were replicated in an independent, prospective cohort. These findings underscore the potential importance of amino acid metabolism early in the pathogenesis of diabetes, and suggest that amino acid profiles could aid in diabetes risk assessment. 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 couldaid in diabetes risk assessment. 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.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. |
| Audience | Academic |
| Author | Fernandez, Céline Souza, Amanda Vasan, Ramachandran S Cheng, Susan Wang, Thomas J Carr, Stephen A O'Donnell, Christopher J Rhee, Eugene P McCabe, Elizabeth Gerszten, Robert E Jacques, Paul F Larson, Martin G Florez, Jose C Lewis, Gregory D Clish, Clary B Mootha, Vamsi K Fox, Caroline S Melander, Olle |
| AuthorAffiliation | 4 Diabetes Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 9 Division of Endocrinology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 6 Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA 3 Renal Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 1 Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 10 National Heart, Lung & Blood Institute Division of Intramural Research, Bethesda, MD 14 Department of Clinical Sciences, Malmö 13 Department of Experimental Medical Science 11 Jean Mayer USDA Human Nutrition Research Center, Tufts University, Boston, MA 5 Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 8 Division of Cardiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 2 Cardiology Division, Massachusetts General Hospital, Harvard Me |
| AuthorAffiliation_xml | – name: 8 Division of Cardiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA – name: 1 Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA – name: 2 Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA – name: 5 Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA – name: 14 Department of Clinical Sciences, Malmö – name: 3 Renal Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA – name: 9 Division of Endocrinology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA – name: 13 Department of Experimental Medical Science – name: 7 Cardiology Section, Boston Medical Center, Boston University School of Medicine, Boston, MA – name: 10 National Heart, Lung & Blood Institute Division of Intramural Research, Bethesda, MD – name: 12 Broad Institute of MIT and Harvard, Cambridge, MA – name: 4 Diabetes Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA – name: 6 Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA – name: 11 Jean Mayer USDA Human Nutrition Research Center, Tufts University, Boston, MA |
| Author_xml | – sequence: 1 givenname: Thomas J surname: Wang fullname: Wang, Thomas J email: tjwang@partners.org organization: Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine – sequence: 2 givenname: Martin G surname: Larson fullname: Larson, Martin G organization: Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Department of Mathematics and Statistics, Boston University – sequence: 3 givenname: Ramachandran S surname: Vasan fullname: Vasan, Ramachandran S organization: Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Cardiology Section, Boston Medical Center, Boston University School of Medicine – sequence: 4 givenname: Susan surname: Cheng fullname: Cheng, Susan organization: Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Division of Cardiology, Brigham and Women's Hospital, Harvard Medical School – sequence: 5 givenname: Eugene P surname: Rhee fullname: Rhee, Eugene P organization: Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Renal Division, Massachusetts General Hospital, Harvard Medical School, Broad Institute of MIT and Harvard – sequence: 6 givenname: Elizabeth surname: McCabe fullname: McCabe, Elizabeth organization: Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine – sequence: 7 givenname: Gregory D surname: Lewis fullname: Lewis, Gregory D organization: Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Broad Institute of MIT and Harvard – sequence: 8 givenname: Caroline S surname: Fox fullname: Fox, Caroline S organization: Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Division of Endocrinology, Brigham and Women's Hospital, Harvard Medical School, Division of Intramural Research, National Heart, Lung, and Blood Institute – sequence: 9 givenname: Paul F surname: Jacques fullname: Jacques, Paul F organization: Jean Mayer US Department of Agriculture Human Nutrition Research Center, Tufts University – sequence: 10 givenname: Céline surname: Fernandez fullname: Fernandez, Céline organization: Department of Experimental Medical Science, Lund University, Malmö – sequence: 11 givenname: Christopher J surname: O'Donnell fullname: O'Donnell, Christopher J organization: Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Broad Institute of MIT and Harvard – sequence: 12 givenname: Stephen A surname: Carr fullname: Carr, Stephen A organization: Broad Institute of MIT and Harvard – sequence: 13 givenname: Vamsi K surname: Mootha fullname: Mootha, Vamsi K organization: Broad Institute of MIT and Harvard, Diabetes Unit, Massachusetts General Hospital, Harvard Medical School, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School – sequence: 14 givenname: Jose C surname: Florez fullname: Florez, Jose C organization: Broad Institute of MIT and Harvard, Diabetes Unit, Massachusetts General Hospital, Harvard Medical School – sequence: 15 givenname: Amanda surname: Souza fullname: Souza, Amanda organization: Broad Institute of MIT and Harvard – sequence: 16 givenname: Olle surname: Melander fullname: Melander, Olle organization: Department of Clinical Sciences, Lund University – sequence: 17 givenname: Clary B surname: Clish fullname: Clish, Clary B organization: Broad Institute of MIT and Harvard – sequence: 18 givenname: Robert E surname: Gerszten fullname: Gerszten, Robert E email: rgerszten@partners.org organization: Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Broad Institute of MIT and Harvard |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/21423183$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | Springer Nature America, Inc. 2011 COPYRIGHT 2011 Nature Publishing Group Copyright Nature Publishing Group Apr 2011 |
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| CorporateAuthor | Lunds universitet Profile areas and other strong research environments Department of Clinical Sciences, Malmö Lund University Kardiovaskulär forskning - hypertoni Strategiska forskningsområden (SFO) EpiHealth: Epidemiology for Health EXODIAB: Excellence of Diabetes Research in Sweden Faculty of Medicine Strategic research areas (SRA) Medicinska fakulteten Profilområden och andra starka forskningsmiljöer Cardiovascular Research - Hypertension Institutionen för kliniska vetenskaper, Malmö |
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| Snippet | Amino acid profiles could aid in diabetes risk assessment, as a five-amino-acid signature had highly significant associations with the development of future... Emerging technologies allow the high-throughput profiling of metabolic status from a blood specimen (metabolomics). We investigated whether metabolite profiles... |
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| Title | Metabolite profiles and the risk of developing diabetes |
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