TY - JOUR
T1 - Circulating metabolite predictors of glycemia in middle-aged men and women
AU - Würtz, Peter
AU - Tiainen, Mika
AU - Mak̈inen, Ville Petteri
AU - Kangas, Antti J.
AU - Soininen, Pasi
AU - Saltevo, Juha
AU - Keinan̈en-Kiukaanniemi, Sirkka
AU - Mäntyselkä, Pekka
AU - Lehtimak̈i, Terho
AU - Laakso, Markku
AU - Jula, Antti
AU - Kähönen, Mika
AU - Vanhala, Mauno
AU - Ala-Korpela, Mika
PY - 2012/8
Y1 - 2012/8
N2 - 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 acidmeasures, were cross-sectionally associated with fasting and/or postload glucose (P < 0.001). Among thesemetabolic intermediates, branched-chain amino acids, phenylalanine, and a1- 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 acidmetabolismprecede 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.
AB - 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 acidmeasures, were cross-sectionally associated with fasting and/or postload glucose (P < 0.001). Among thesemetabolic intermediates, branched-chain amino acids, phenylalanine, and a1- 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 acidmetabolismprecede 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.
UR - http://www.scopus.com/inward/record.url?scp=84864386138&partnerID=8YFLogxK
U2 - 10.2337/dc11-1838
DO - 10.2337/dc11-1838
M3 - Article
C2 - 22563043
AN - SCOPUS:84864386138
VL - 35
SP - 1749
EP - 1756
JO - Diabetes Care
JF - Diabetes Care
SN - 0149-5992
IS - 8
ER -