Branched chain and aromatic amino acids change acutely following two medical therapies for type 2 diabetes mellitus

Geoffrey A. Walford, Jaclyn Davis, A. Sofia Warner, Rachel J. Ackerman, Liana K. Billings, Bindu Chamarthi, Rebecca R. Fanelli, Alicia M. Hernandez, Chunmei Huang, Sabina Q. Khan, Katherine R. Littleton, Janet Lo, Rita M. McCarthy, Eugene P. Rhee, Amy Deik, Elliot Stolerman, Andrew Taylor, Margo S. Hudson, Thomas J. Wang, David AltshulerRichard W. Grant, Clary B. Clish, Robert E. Gerszten, Jose C. Florez

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


Objective Elevated circulating levels of branched chain and aromatic amino acids (BCAA/AAAs) are associated with insulin resistance and incident type 2 diabetes (T2D). BCAA/AAAs decrease acutely during an oral glucose tolerance test (OGTT), a diagnostic test for T2D. It is unknown whether changes in BCAA/AAAs also signal an early response to commonly used medical therapies for T2D. Materials and Methods A liquid chromatography-mass spectrometry approach was used to measure BCAA/AAAs in 30 insulin sensitive (IS) and 30 insulin resistant (IR) subjects before and after: 1) one dose of a sulfonylurea medication, glipizide, 5 mg orally; 2) two days of twice daily metformin 500 mg orally; and 3) a 75-g OGTT. Percent change in BCAA/AAAs was determined after each intervention. Results Following glipizide, which increased insulin and decreased glucose in both subject groups, BCAA/AAAs decreased in the IS subjects only (all P < 0.05). Following metformin, which decreased glucose and insulin in only the IR subjects, 4 BCAA/AAAs increased in the IR subjects at or below P = 0.05, and none changed in the IS subjects. Following OGTT, which increased glucose and insulin in all subjects, BCAA/AAAs decreased in all subjects (P < 0.05). Conclusions BCAA/AAAs changed acutely during glipizide and metformin administration, and the magnitude and direction of change differed by the insulin resistance status of the individual and the intervention. These results indicate that BCAA/AAAs may be useful biomarkers for monitoring the early response to therapeutic interventions for T2D.

Original languageEnglish (US)
Pages (from-to)1772-1778
Number of pages7
JournalMetabolism: clinical and experimental
Issue number12
StatePublished - Dec 2013
Externally publishedYes


  • aromatic amino acids
  • branched chain amino acids

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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