Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS)
Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS)
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DOI：
10.2337/dc15-2284
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发表时间：
2016-04-01
期刊：
影响因子：
16.2
通讯作者：
Hanley, Anthony J.
中科院分区：
文献类型：
--
作者：
Lee, C. Christine;Watkins, Steve M.;Hanley, Anthony J.
最近使用非靶向代谢组学方法的研究表明，血浆支链氨基酸（BCAAs）与糖尿病相关。然而，关于血浆支链氨基酸在糖尿病基础代谢异常中的作用以及这些关系在糖尿病高危人群中是否一致，我们知之甚少。我们在一个多种族的队列中调查了支链氨基酸与胰岛素敏感性（SI）、急性胰岛素反应（AIR）和胰岛素代谢清除率（MCRI）的关系。研究设计和方法在685名非糖尿病的胰岛素抵抗动脉粥样硬化研究（IRAS）参与者中（290名白人，165名非洲裔美国人和230名西班牙裔），我们测量了血浆BCAA（缬氨酸、亮氨酸和异亮氨酸的总和）和SI，AIR，血浆BCAAs水平与SI和MCRI呈负相关，与空腹胰岛素呈正相关在针对潜在混杂因素调整的回归模型中（SI的β = 20.0012 [95% CI 20.0018，20.00059]，P < 0.001; MCRI的β = 20.0013 [95% CI 20.0018，20.00082]，P < 0.001; β = 0.0015 [95%CI 0.0008，0.0023]，P < 0.001（空腹胰岛素）。BCAA与SI的相关性因种族而显著改变，仅在白人和西班牙裔中具有显著性。在白人和西班牙裔中，血浆支链氨基酸升高与糖尿病事件相关（血浆支链氨基酸每增加1个标准差的多变量校正比值比：1.67 [95% CI 1.21，2.29]，P = 0.002），但在非裔美国人中则不相关。血浆BCAAs与SI调整的AIR. CONCLUSIONSPLASMBCAAs与糖尿病和潜在的代谢异常事件，虽然协会普遍较强的白人和西班牙裔。
OBJECTIVERecent studies using untargeted metabolomics approaches have suggested that plasma branched-chain amino acids (BCAAs) are associated with incident diabetes. However, little is known about the role of plasma BCAAs in metabolic abnormalities underlying diabetes and whether these relationships are consistent across ethnic populations at high risk for diabetes. We investigated the associations of BCAAs with insulin sensitivity (SI), acute insulin response (AIR), and metabolic clearance of insulin (MCRI) in a multiethnic cohort.RESEARCH DESIGN AND METHODSIn 685 participants without diabetes of the Insulin Resistance Atherosclerosis Study (IRAS) (290 Caucasians, 165 African Americans, and 230 Hispanics), we measured plasma BCAAs (sum of valine, leucine, and isoleucine) by mass spectrometry and SI, AIR, and MCRI by frequently sampled intravenous glucose tolerance tests.RESULTSElevated plasma BCAAs were inversely associated with SI and MCRI and positively associated with fasting insulin in regression models adjusted for potential confounders (beta = 20.0012 [95% CI20.0018,20.00059], P < 0.001 for SI; beta = 20.0013 [95% CI 20.0018, 20.00082], P < 0.001 for MCRI; and beta = 0.0015 [95% CI 0.0008, 0.0023], P < 0.001 for fasting insulin). The association of BCAA with SI was significantly modified by ethnicity, with the association only being significant in Caucasians and Hispanics. Elevated plasma BCAAs were associated with incident diabetes in Caucasians and Hispanics (multivariable-adjusted odds ratio per 1-SD increase in plasma BCAAs: 1.67 [95% CI 1.21, 2.29], P = 0.002) but not in African Americans. Plasma BCAAs were not associated with SI-adjusted AIR.CONCLUSIONSPlasma BCAAs are associated with incident diabetes and underlying metabolic abnormalities, although the associations were generally stronger in Caucasians and Hispanics.