title: Metabolomic profiling of amino acids and β-cell function relative to insulin sensitivity in youth.
abstract: BACKGROUND
  In longitudinal studies of adults, elevated amino acid (AA) concentrations predicted future type 2 diabetes mellitus (T2DM).
  
  
  OBJECTIVE
  The aim of the present investigation was to examine whether increased plasma AA concentrations are associated with impaired β-cell function relative to insulin sensitivity [i.e. disposition index (DI)], a predictor of T2DM development.
  
  
  METHODS
  Metabolomic analysis for fasting plasma AAs was performed by tandem mass spectrometry in 139 normal-weight and obese adolescents with and without dysglycemia. First-phase insulin secretion was evaluated by a hyperglycemic (∼225 mg/dl) clamp and insulin sensitivity by a hyperinsulinemic-euglycemic clamp. DI was calculated as the product of first-phase insulin and insulin sensitivity.
  
  
  RESULTS
  DI was positively associated with branched-chain AAs (leucine/isoleucine and valine; r = 0.27 and 0.29, P = 0.001), neutrally transported AAs (phenylalanine and methionine; r = 0.30 and 0.35, P < 0.001), basic AAs (histidine and arginine; r = 0.28 and 0.23, P ≤ 0.007), serine (r = 0.35, P < 0.001), glycine (r = 0.26, P = 0.002), and branched-chain AAs-derived intermediates C3, C4, and C5 acylcarnitine (range r = 0.18-0.19, P ≤ 0.04).
  
  
  CONCLUSIONS
  In youth, increased plasma AA concentrations are not associated with a heightened metabolic risk profile for T2DM; rather, they are positively associated with β-cell function relative to insulin sensitivity. These contrasting observations between adults and youth may be a reflection of developmental differences along the lifespan dependent on the combined impact of the aging process together with the impact of progressive obesity.
authors.affiliation: Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, Pennsylvania 15224, USA.
authors.forename: Sara F
authors.initials: SF
authors.lastname: Michaliszyn
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Sjaarda
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Mihalik
authors.forename: Sojung
authors.initials: S
authors.lastname: Lee
authors.forename: Fida
authors.initials: F
authors.lastname: Bacha
authors.forename: Donald H
authors.initials: DH
authors.lastname: Chace
authors.forename: Victor R
authors.initials: VR
authors.lastname: De Jesus
authors.forename: Jerry
authors.initials: J
authors.lastname: Vockley
authors.forename: Silva A
authors.initials: SA
authors.lastname: Arslanian
mesh_terms: D000293:Adolescent; D000596:Amino Acids / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D009765:Obesity / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D011237:Predictive Value of Tests
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D007328:Insulin