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

Branched chain and aromatic amino acids change acutely following two medical therapies for type 2 diabetes mellitus.
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DOI:
10.1016/j.metabol.2013.07.003
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发表时间:
2013-12
影响因子:
9.8
通讯作者:
Florez, Jose C.
Florez, Jose C.
中科院分区:
医学1区
文献类型:
--
作者:
Walford, Geoffrey A.;Davis, Jaclyn;Warner, A. Sofia;Ackerman, Rachel J.;Billings, Liana K.;Chamarthi, Bindu;Fanelli, Rebecca R.;Hernandez, Alicia M.;Huang, Chunmei;Khan, Sabina Q.;Littleton, Katherine R.;Lo, Janet;McCarthy, Rita M.;Rhee, Eugene P.;Deik, Amy;Stolerman, Elliot;Taylor, Andrew;Hudson, Margo S.;Wang, Thomas J.;Altshuler, David;Grant, Richard W.;Clish, Clary B.;Gerszten, Robert E.;Florez, Jose C.

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支链氨基酸和芳香氨基酸 (BCAA/AAA) 循环水平升高与胰岛素抵抗和 2 型糖尿病 (T2D) 相关。在口服葡萄糖耐量试验 (OGTT)(一种 T2D 诊断试验)中,BCAA/AAA 会急剧下降。目前尚不清楚 BCAA/AAA 的变化是否也预示着对 T2D 常用药物治疗的早期反应。使用液相色谱-质谱法测量 30 名胰岛素敏感 (IS) 和 30 名胰岛素抵抗 (IR) 受试者前后的 BCAA/AAA:1) 口服一剂磺酰脲类药物格列吡嗪,5 mg; 2) 口服二甲双胍500mg,每日两次,两天; 3) 75 克 OGTT。每次干预后确定 BCAA/AAA 的变化百分比。格列吡嗪增加了两个受试者组的胰岛素水平并降低了血糖,之后仅 IS 受试者的 BCAA/AAA 有所下降(所有 P<0.05)。二甲双胍仅降低 IR 受试者的血糖和胰岛素,之后 IR 受试者中的 4 种 BCAA/AAA 增加,达到或低于 P=0.05,而 IS 受试者中没有任何变化。 OGTT 后,所有受试者的血糖和胰岛素均增加,所有受试者的 BCAA/AAA 均减少 (P<0.05)。 BCAA/AAA在格列吡嗪和二甲双胍给药期间发生急剧变化,并且变化的幅度和方向因个体的胰岛素抵抗状态和干预而不同。这些结果表明 BCAA/AAA 可能是监测 T2D 治疗干预早期反应的有用生物标志物。
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. 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-gram OGTT. Percent change in BCAA/AAAs was determined after each intervention. 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). 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.
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