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Metabolism DOI:10.1016/j.metabol.2013.07.003

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

Publication TypeJournal Article
Year of Publication2013
AuthorsWalford, GA, Davis, J, A Warner, S, Ackerman, RJ, Billings, LK, Chamarthi, B, Fanelli, RR, Hernandez, AM, Huang, C, Khan, SQ, Littleton, KR, Lo, J, McCarthy, RM, Rhee, EP, Deik, A, Stolerman, E, Taylor, A, Hudson, MS, Wang, TJ, Altshuler, D, Grant, RW, Clish, CB, Gerszten, RE, Florez, JC
Date Published2013 Dec
KeywordsAged, Amino Acids, Aromatic, Amino Acids, Branched-Chain, Biomarkers, Blood Glucose, Diabetes Mellitus, Type 2, Female, Glipizide, Humans, Hypoglycemic Agents, Insulin, Insulin Resistance, Male, Metformin, Middle Aged, Spectrum Analysis

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

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.


Alternate JournalMetab. Clin. Exp.
PubMed ID23953891
PubMed Central IDPMC3833885
Grant ListT32 DK007028 / DK / NIDDK NIH HHS / United States
DK007028 / DK / NIDDK NIH HHS / United States
R01 DK088214 / DK / NIDDK NIH HHS / United States
R01 DK088214.A1 / DK / NIDDK NIH HHS / United States
UL1 RR025758 / RR / NCRR NIH HHS / United States
UL1 RR 025758 / RR / NCRR NIH HHS / United States