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

Featured Article :. Circulating Metabolite Predictors of Glycemia in Middle-Aged Men and Women.

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

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  1. Featured Article: Circulating Metabolite Predictors of Glycemia in Middle-Aged Men and Women Peter Würtz, Ph.D., Mika Tiainen, M.S.C., Ville-Petteri Mäkinen, D.S.C., Antti J. Kangas, M.S.C., Pasi Soininen, Ph.D., Juha Saltevo, M.D., Ph.D., Sirkka Keinänen-Kiukaanniemi, M.D., Ph.D., Pekka Mäntyselkä, M.D., Ph.D., Terho Lehtimäki, M.D., Ph.D., Markku Laakso, M.D., Ph.D., Antti Jula, M.D., Ph.D., Mika Kähönen, M.D., Ph.D., Mauno Vanhala, M.D., Ph.D., Mika Ala-Korpela, Ph.D. Diabetes Care Volume 35: 1749-1756 August, 2012

  2. Study Objective • Metabolite predictors of deteriorating glucose tolerance may elucidate the pathogenesis of type 2 diabetes • Study investigated associations of circulating metabolites from high-throughput profiling with fasting and postload glycemia cross-sectionally and prospectively on the population level Würtz P et al. Diabetes Care 2012;35:1749-1756

  3. Study Design • Oral glucose tolerance assessed in 2 Finnish population-based studies consisting of 1,873 individuals (mean age 52 years, 58% women) • OGTT reexamined after 6.5 years for 618 individuals in one of the cohorts • Metabolites quantified by NMR spectroscopy from fasting serum samples • Associations were studied by linear regression models adjusted for established risk factors Würtz P et al. Diabetes Care 2012;35:1749-1756

  4. Results • 19 circulating metabolites, including amino acids, gluconeogenic substrates, and fatty acid measures cross-sectionally associated with fasting and/or postload glucose (P< 0.001) • Branched-chain amino acids, phenylalanine, and α1-acid glycoprotein predicted both fasting and 2-h glucose at 6.5-year follow-up (P< 0.05) • Alanine, lactate, pyruvate, and tyrosine associated with 6.5-year postload glucose (P = 0.003–0.04) Würtz P et al. Diabetes Care 2012;35:1749-1756

  5. Würtz P et al. Diabetes Care 2012;35:1749-1756

  6. Würtz P et al. Diabetes Care 2012;35:1749-1756

  7. Würtz P et al. Diabetes Care 2012;35:1749-1756

  8. Würtz P et al. Diabetes Care 2012;35:1749-1756

  9. Conclusions • Alterations in branched-chain and aromatic amino acid metabolism precede hyperglycemia in the general population • Alanine, lactate, and pyruvate were predictive of postchallenge glucose • These gluconeogenic precursors are potential markers of long-term impaired insulin sensitivity that may relate to attenuated glucose tolerance later in life Würtz P et al. Diabetes Care 2012;35:1749-1756

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