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Circulating Metabolite Predictors of Glycemia in Middle-Aged Men and Women

OBJECTIVE: Metabolite predictors of deteriorating glucose tolerance may elucidate the pathogenesis of type 2 diabetes. We investigated associations of circulating metabolites from high-throughput profiling with fasting and postload glycemia cross-sectionally and prospectively on the population level...

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Autores principales: Würtz, Peter, Tiainen, Mika, Mäkinen, Ville-Petteri, Kangas, Antti J., Soininen, Pasi, Saltevo, Juha, Keinänen-Kiukaanniemi, Sirkka, Mäntyselkä, Pekka, Lehtimäki, Terho, Laakso, Markku, Jula, Antti, Kähönen, Mika, Vanhala, Mauno, Ala-Korpela, Mika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402262/
https://www.ncbi.nlm.nih.gov/pubmed/22563043
http://dx.doi.org/10.2337/dc11-1838
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author Würtz, Peter
Tiainen, Mika
Mäkinen, Ville-Petteri
Kangas, Antti J.
Soininen, Pasi
Saltevo, Juha
Keinänen-Kiukaanniemi, Sirkka
Mäntyselkä, Pekka
Lehtimäki, Terho
Laakso, Markku
Jula, Antti
Kähönen, Mika
Vanhala, Mauno
Ala-Korpela, Mika
author_facet Würtz, Peter
Tiainen, Mika
Mäkinen, Ville-Petteri
Kangas, Antti J.
Soininen, Pasi
Saltevo, Juha
Keinänen-Kiukaanniemi, Sirkka
Mäntyselkä, Pekka
Lehtimäki, Terho
Laakso, Markku
Jula, Antti
Kähönen, Mika
Vanhala, Mauno
Ala-Korpela, Mika
author_sort Würtz, Peter
collection PubMed
description OBJECTIVE: Metabolite predictors of deteriorating glucose tolerance may elucidate the pathogenesis of type 2 diabetes. We investigated associations of circulating metabolites from high-throughput profiling with fasting and postload glycemia cross-sectionally and prospectively on the population level. RESEARCH DESIGN AND METHODS: Oral glucose tolerance was assessed in two Finnish, population-based studies consisting of 1,873 individuals (mean age 52 years, 58% women) and reexamined after 6.5 years for 618 individuals in one of the cohorts. Metabolites were quantified by nuclear magnetic resonance spectroscopy from fasting serum samples. Associations were studied by linear regression models adjusted for established risk factors. RESULTS: Nineteen circulating metabolites, including amino acids, gluconeogenic substrates, and fatty acid measures, were cross-sectionally associated with fasting and/or postload glucose (P < 0.001). Among these metabolic intermediates, branched-chain amino acids, phenylalanine, and α1-acid glycoprotein were predictors of both fasting and 2-h glucose at 6.5-year follow-up (P < 0.05), whereas alanine, lactate, pyruvate, and tyrosine were uniquely associated with 6.5-year postload glucose (P = 0.003–0.04). None of the fatty acid measures were prospectively associated with glycemia. Changes in fatty acid concentrations were associated with changes in fasting and postload glycemia during follow-up; however, changes in branched-chain amino acids did not follow glucose dynamics, and gluconeogenic substrates only paralleled changes in fasting glucose. CONCLUSIONS: Alterations in branched-chain and aromatic amino acid metabolism precede hyperglycemia in the general population. Further, alanine, lactate, and pyruvate were predictive of postchallenge glucose exclusively. These gluconeogenic precursors are potential markers of long-term impaired insulin sensitivity that may relate to attenuated glucose tolerance later in life.
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spelling pubmed-34022622013-08-01 Circulating Metabolite Predictors of Glycemia in Middle-Aged Men and Women Würtz, Peter Tiainen, Mika Mäkinen, Ville-Petteri Kangas, Antti J. Soininen, Pasi Saltevo, Juha Keinänen-Kiukaanniemi, Sirkka Mäntyselkä, Pekka Lehtimäki, Terho Laakso, Markku Jula, Antti Kähönen, Mika Vanhala, Mauno Ala-Korpela, Mika Diabetes Care Original Research OBJECTIVE: Metabolite predictors of deteriorating glucose tolerance may elucidate the pathogenesis of type 2 diabetes. We investigated associations of circulating metabolites from high-throughput profiling with fasting and postload glycemia cross-sectionally and prospectively on the population level. RESEARCH DESIGN AND METHODS: Oral glucose tolerance was assessed in two Finnish, population-based studies consisting of 1,873 individuals (mean age 52 years, 58% women) and reexamined after 6.5 years for 618 individuals in one of the cohorts. Metabolites were quantified by nuclear magnetic resonance spectroscopy from fasting serum samples. Associations were studied by linear regression models adjusted for established risk factors. RESULTS: Nineteen circulating metabolites, including amino acids, gluconeogenic substrates, and fatty acid measures, were cross-sectionally associated with fasting and/or postload glucose (P < 0.001). Among these metabolic intermediates, branched-chain amino acids, phenylalanine, and α1-acid glycoprotein were predictors of both fasting and 2-h glucose at 6.5-year follow-up (P < 0.05), whereas alanine, lactate, pyruvate, and tyrosine were uniquely associated with 6.5-year postload glucose (P = 0.003–0.04). None of the fatty acid measures were prospectively associated with glycemia. Changes in fatty acid concentrations were associated with changes in fasting and postload glycemia during follow-up; however, changes in branched-chain amino acids did not follow glucose dynamics, and gluconeogenic substrates only paralleled changes in fasting glucose. CONCLUSIONS: Alterations in branched-chain and aromatic amino acid metabolism precede hyperglycemia in the general population. Further, alanine, lactate, and pyruvate were predictive of postchallenge glucose exclusively. These gluconeogenic precursors are potential markers of long-term impaired insulin sensitivity that may relate to attenuated glucose tolerance later in life. American Diabetes Association 2012-08 2012-07-14 /pmc/articles/PMC3402262/ /pubmed/22563043 http://dx.doi.org/10.2337/dc11-1838 Text en © 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Research
Würtz, Peter
Tiainen, Mika
Mäkinen, Ville-Petteri
Kangas, Antti J.
Soininen, Pasi
Saltevo, Juha
Keinänen-Kiukaanniemi, Sirkka
Mäntyselkä, Pekka
Lehtimäki, Terho
Laakso, Markku
Jula, Antti
Kähönen, Mika
Vanhala, Mauno
Ala-Korpela, Mika
Circulating Metabolite Predictors of Glycemia in Middle-Aged Men and Women
title Circulating Metabolite Predictors of Glycemia in Middle-Aged Men and Women
title_full Circulating Metabolite Predictors of Glycemia in Middle-Aged Men and Women
title_fullStr Circulating Metabolite Predictors of Glycemia in Middle-Aged Men and Women
title_full_unstemmed Circulating Metabolite Predictors of Glycemia in Middle-Aged Men and Women
title_short Circulating Metabolite Predictors of Glycemia in Middle-Aged Men and Women
title_sort circulating metabolite predictors of glycemia in middle-aged men and women
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402262/
https://www.ncbi.nlm.nih.gov/pubmed/22563043
http://dx.doi.org/10.2337/dc11-1838
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