title: Branched-chain and aromatic amino acids are predictors of insulin resistance in young adults.
abstract: OBJECTIVE
  Branched-chain and aromatic amino acids are associated with the risk for future type 2 diabetes; however, the underlying mechanisms remain elusive. We tested whether amino acids predict insulin resistance index in healthy young adults.
  
  
  METHODS
  Circulating isoleucine, leucine, valine, phenylalanine, tyrosine, and six additional amino acids were quantified in 1,680 individuals from the population-based Cardiovascular Risk in Young Finns Study (baseline age 32 ± 5 years; 54% women). Insulin resistance was estimated by homeostasis model assessment (HOMA) at baseline and 6-year follow-up. Amino acid associations with HOMA of insulin resistance (HOMA-IR) and glucose were assessed using regression models adjusted for established risk factors. We further examined whether amino acid profiling could augment risk assessment of insulin resistance (defined as 6-year HOMA-IR >90th percentile) in early adulthood.
  
  
  RESULTS
  Isoleucine, leucine, valine, phenylalanine, and tyrosine were associated with HOMA-IR at baseline and for men at 6-year follow-up, while for women only leucine, valine, and phenylalanine predicted 6-year HOMA-IR (P < 0.05). None of the other amino acids were prospectively associated with HOMA-IR. The sum of branched-chain and aromatic amino acid concentrations was associated with 6-year insulin resistance for men (odds ratio 2.09 [95% CI 1.38-3.17]; P = 0.0005); however, including the amino acid score in prediction models did not improve risk discrimination.
  
  
  CONCLUSIONS
  Branched-chain and aromatic amino acids are markers of the development of insulin resistance in young, normoglycemic adults, with most pronounced associations for men. These findings suggest that the association of branched-chain and aromatic amino acids with the risk for future diabetes is at least partly mediated through insulin resistance.
authors.affiliation: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland. peter.wurtz@helsinki.fi
authors.forename: Peter
authors.initials: P
authors.lastname: Würtz
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Kangas
authors.forename: Tapani
authors.initials: T
authors.lastname: Rönnemaa
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.forename: Jorma S
authors.initials: JS
authors.lastname: Viikari
authors.forename: Olli T
authors.initials: OT
authors.lastname: Raitakari
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000097:blood*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D007532:Isoleucine / Q000097:blood; D007930:Leucine / Q000097:blood; D008297:Male; D010649:Phenylalanine / Q000097:blood; D014443:Tyrosine / Q000097:blood; D014633:Valine / Q000097:blood; D055815:Young Adult
chemical_list: D000596:Amino Acids; D007532:Isoleucine; D014443:Tyrosine; D010649:Phenylalanine; D007930:Leucine; D014633:Valine