Metabolomic profiling of amino acids and β-cell function relative to insulin sensitivity in youth

J Clin Endocrinol Metab. 2012 Nov;97(11):E2119-24. doi: 10.1210/jc.2012-2170. Epub 2012 Sep 13.


Context: 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.

Design, setting, and participants: 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).

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Amino Acids / blood*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology
  • Female
  • Humans
  • Insulin / metabolism
  • Insulin Resistance / physiology*
  • Insulin-Secreting Cells / physiology*
  • Male
  • Obesity / blood
  • Obesity / metabolism*
  • Obesity / physiopathology
  • Predictive Value of Tests


  • Amino Acids
  • Blood Glucose
  • Insulin