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Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS).

Publication ,  Journal Article
Lee, CC; Watkins, SM; Lorenzo, C; Wagenknecht, LE; Il'yasova, D; Chen, Y-DI; Haffner, SM; Hanley, AJ
Published in: Diabetes Care
April 2016

OBJECTIVE: Recent 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 METHODS: In 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. RESULTS: Elevated plasma BCAAs were inversely associated with SI and MCRI and positively associated with fasting insulin in regression models adjusted for potential confounders (β = -0.0012 [95% CI -0.0018, -0.00059], P < 0.001 for SI; β = -0.0013 [95% CI -0.0018, -0.00082], P < 0.001 for MCRI; and β = 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. CONCLUSIONS: Plasma BCAAs are associated with incident diabetes and underlying metabolic abnormalities, although the associations were generally stronger in Caucasians and Hispanics.

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Published In

Diabetes Care

DOI

EISSN

1935-5548

Publication Date

April 2016

Volume

39

Issue

4

Start / End Page

582 / 588

Location

United States

Related Subject Headings

  • White People
  • Multivariate Analysis
  • Middle Aged
  • Male
  • Linear Models
  • Insulin Resistance
  • Insulin
  • Incidence
  • Humans
  • Hispanic or Latino
 

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Chicago
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MLA
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Lee, C. C., Watkins, S. M., Lorenzo, C., Wagenknecht, L. E., Il’yasova, D., Chen, Y.-D., … Hanley, A. J. (2016). Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS). Diabetes Care, 39(4), 582–588. https://doi.org/10.2337/dc15-2284
Lee, C Christine, Steve M. Watkins, Carlos Lorenzo, Lynne E. Wagenknecht, Dora Il’yasova, Yii-Der I. Chen, Steven M. Haffner, and Anthony J. Hanley. “Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS).Diabetes Care 39, no. 4 (April 2016): 582–88. https://doi.org/10.2337/dc15-2284.
Lee CC, Watkins SM, Lorenzo C, Wagenknecht LE, Il’yasova D, Chen Y-DI, et al. Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS). Diabetes Care. 2016 Apr;39(4):582–8.
Lee, C. Christine, et al. “Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS).Diabetes Care, vol. 39, no. 4, Apr. 2016, pp. 582–88. Pubmed, doi:10.2337/dc15-2284.
Lee CC, Watkins SM, Lorenzo C, Wagenknecht LE, Il’yasova D, Chen Y-DI, Haffner SM, Hanley AJ. Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS). Diabetes Care. 2016 Apr;39(4):582–588.

Published In

Diabetes Care

DOI

EISSN

1935-5548

Publication Date

April 2016

Volume

39

Issue

4

Start / End Page

582 / 588

Location

United States

Related Subject Headings

  • White People
  • Multivariate Analysis
  • Middle Aged
  • Male
  • Linear Models
  • Insulin Resistance
  • Insulin
  • Incidence
  • Humans
  • Hispanic or Latino