Peter W

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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
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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 2012351749-1756
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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 2012351749-1756
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Results

• 19 circulating metabolites, including amino
  acids, gluconeogenic substrates, and fatty acid
  measures cross-sectionally associated with
  fasting and/or postload glucose (Plt 0.001)
• Branched-chain amino acids, phenylalanine, and
  a1-acid glycoprotein predicted both fasting and
  2-h glucose at 6.5-year follow-up (Plt 0.05)
•  
• Alanine, lactate, pyruvate, and tyrosine
  associated with 6.5-year postload glucose (P
  0.0030.04)

Würtz P et al. Diabetes Care 2012351749-1756
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Würtz P et al. Diabetes Care 2012351749-1756
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Würtz P et al. Diabetes Care 2012351749-1756
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Würtz P et al. Diabetes Care 2012351749-1756
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Würtz P et al. Diabetes Care 2012351749-1756
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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 2012351749-1756